CD38-binding agents and uses thereof

Abstract

To provide an agent that binds to CD38.SOLUTION: Provided is an agent comprising an antibody-binding moiety, a target-binding moiety, and, optionally, a linker moiety, the target-binding moiety specifically binding to CD38.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 62 / 870,633, filed July 3, 2019, and U.S. Provisional Application No. 62 / 951,765, filed December 20, 2019, each of which is incorporated by reference in its entirety.

[0002] The present disclosure provides, among other things, techniques (eg, compounds, compositions, and methods thereof) useful for treating, for example, various conditions, disorders, or diseases. [Background technology]

[0003] The activity of the immune system can be utilized to prevent or treat a variety of conditions, disorders, and diseases. Summary of the Invention

[0004] In some embodiments, the present disclosure provides technologies (e.g., compounds, compositions, methods, etc.) that are particularly useful for recruiting antibodies to damaged or defective tissues (e.g., tumors, certain wounds, etc.), foreign bodies or entities (e.g., infectious agents), and the like, that comprise CD38 or a fragment thereof. In some embodiments, the provided technologies can induce, generate, promote, and / or enhance immune system activity, e.g., antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and the like, against target cells, tissues, objects, and / or entities that express CD38. In some embodiments, the present disclosure is directed to the design, preparation, and use of molecules that can selectively redirect endogenous antibodies to diseased cells (e.g., cancer cells that express CD38) and induce immune system activity (e.g., antibody-directed, cell-mediated immune responses (e.g., cytotoxicity, ADCP, etc.)).

[0005] In some embodiments, the present disclosure provides antibody recruiting molecules (ARMs), comprising an antibody-binding moiety, a target-binding moiety (e.g., one that binds CD38), and, optionally, a linker moiety. In some embodiments, the target-binding moiety confers specificity for the ARM for its target (e.g., disease cells of interest), e.g., through binding of an entity that distinguishes the target from a non-target (e.g., disease cells from another cell type). Among other things, the ARM enables target-specific recruitment of antibodies (e.g., endogenous antibodies, administered antibodies, etc.) via ABT and / or can induce, generate, promote, and / or enhance immune activity (e.g., immune-mediated killing of target cells). In some embodiments, the provided technology includes an ARM comprising a target-binding moiety that binds CD38, and can selectively recruit antibodies against targets (e.g., cancer cells) that express CD38 and / or can induce, generate, promote, and / or enhance immune activity (e.g., ADCC, ADCP, etc.) against such target cells. In some embodiments, the CD38-expressing target cells are cancer cells. In some embodiments, the agents provided herein (e.g., ARMs that bind to CD38) are particularly useful for preventing and / or treating CD38-associated conditions, disorders, or diseases (e.g., various types of CD38-associated cancers).

[0006] Among other things, the present disclosure encompasses the recognition that, without intending to be limited by any particular theory, certain immunotherapies targeting CD38-expressing targets, such as CD38 antibodies, suffer from one or more side effects (e.g., toxicity) due to the reduction and / or depletion of normal cells expressing CD38. For example, as described herein, in some embodiments, CD38 antibodies (e.g., daratumumab) induced a reduction or depletion of CD38-expressing immune effector cells. Among other things, the present disclosure demonstrates that the provided technology can recruit immune components and immune activity to CD38-expressing targets (e.g., cancer cells) with less or no significant reduction or depletion of CD38-expressing immune effector cells compared to CD38 antibodies such as daratumumab.

[0007] In some embodiments, provided compounds (e.g., ARMs) comprise an antibody-binding moiety (universal antibody binding terminus, uABT) that can bind to antibodies of various specificities. Among other things, such ARMs can avoid specific antibody population dependency and / or undesirable effects associated with individual variations in specific antibody populations. In some embodiments, uABTs can bind to the Fc region of antibodies, thereby, among other things, recruiting antibodies of various antigen specificities. In some embodiments, ABTs, e.g., uABTs, can bind to the Fc region of IgG. C In some embodiments, the uABT binds to a conserved site present in the ARM region. In some embodiments, the uABT allows for the recruitment of all IgG subclasses (IgG1, IgG2, IgG3, IgG4). In some embodiments, the uABT preferentially allows for the recruitment of IgG1, IgG2, and / or IgG4. In some embodiments, the uABT binds to IgG molecules but not human IgA or IgM. In some embodiments, the recruitment of antibodies, e.g., IgG subclasses, is dependent on the administered dose of the ARM and / or is independent of the level of antibodies with a particular Fab region in an individual. In some embodiments, useful ABTs are those described in WO2019 / 023501, and various ABTs, including antibody-binding moieties thereof, e.g., uABT, are incorporated herein by reference. One of skill in the art will appreciate that a variety of antibody-binding moieties are available and can be utilized in accordance with the present disclosure.

[0008] In particular, an ARM can recruit antibodies, and the recruited antibodies provide one or more immune activities, for example, via one or more antibody-mediated immune mechanisms. In some embodiments, the recruited antibodies recruit immune cells and / or interact with and / or activate Fc receptors on immune cells. In some embodiments, the recruited antibodies recruit and activate immune cells to inhibit and / or target diseased cells, such as cancer cells. In some embodiments, a provided agent (e.g., an ARM) induces antibody-dependent effector function. In some embodiments, a provided agent (e.g., an ARM) induces complement-dependent cytotoxicity (CDC). In some embodiments, a provided agent (e.g., an ARM) directly induces cytotoxicity. In some embodiments, a provided agent (e.g., an ARM) inhibits biological functions associated with steric hindrance. In some embodiments, a provided agent (e.g., an ARM) induces antibody-dependent cell-mediated viral inhibition (ADCVI). In some embodiments, a provided agent (e.g., an ARM) induces ADCC and kills cancer cells. In some embodiments, provided agents (e.g., ARMs) induce ADCC and kill cancer cells, hi some embodiments, provided agents (e.g., ARMs) induce both ADCC and ADCP.

[0009] In some embodiments, the present disclosure provides: an antibody binding moiety; a target binding moiety; and Optionally, a linker moiety is provided.

[0010] In some embodiments, the target binding moiety is capable of binding to CD38. In some embodiments, the antibody binding moiety is capable of binding to two or more antibodies with different Fab regions. In some embodiments, the antibody binding moiety is capable of binding to two or more antibodies with different antigen specificities. In some embodiments, the antibody binding moiety is capable of binding to the Fc region of different antibodies. In some embodiments, the antibody binding moiety, e.g., a universal antibody binding moiety, binds to the Fc region of an antibody. In some embodiments, the antibody binding moiety, e.g., a universal antibody binding moiety, binds to a conserved Fc region of an antibody. In some embodiments, the antibody binding moiety binds to the Fc region of an IgG antibody. In some embodiments, upon binding to the antibody binding moiety (e.g., at the Fc region), the antibody can still perform all, substantially all, or most of its biological functions. For example, upon binding to the antibody binding moiety, the antibody can recruit and / or activate immune cells, e.g., through interactions with various Fc receptors.

[0011] In some embodiments, the present disclosure provides compounds of general formula I: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is independently defined and described herein. In some embodiments, the agent provided is a compound of Formula I or a salt thereof:

[0012] In some embodiments, a provided agent, e.g., a compound of Formula I, [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described in this disclosure.

[0013] In some embodiments, the provided agent is a compound of formula Ia or a salt thereof. In some embodiments, the present disclosure provides a compound of formula Ia: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described in this disclosure. In some embodiments, the compound of Formula I is provided as a compound of Formula Ia:

[0014] In some embodiments, the provided agent is a compound of formula Ib or a salt thereof. In some embodiments, the present disclosure provides a compound of formula Ib: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described in this disclosure. In some embodiments, the compound of formula I is provided as a compound of formula Ib:

[0015] In some embodiments, the agents and compounds of the present disclosure, and pharmaceutically acceptable compositions thereof, are provided that are effective in recruiting antibodies to diseased cells (e.g., cancer cells). In some embodiments, the present disclosure provides compounds of the general formula II: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is defined and described herein. In some embodiments, the provided agent is a compound of formula II or a salt thereof. In some embodiments, the provided compound of formula I is a compound of formula II or a salt thereof. In some embodiments, the compound having the structure of formula Ia is a compound of formula II.

[0016] In some embodiments, the present disclosure provides compounds of general formula III: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is defined and described herein. In some embodiments, the provided agent is a compound of formula III or a salt thereof. In some embodiments, the provided compound of formula I is a compound of formula III or a salt thereof. In some embodiments, the compound having the structure of formula Ib is a compound of formula III.

[0017] The compounds of the present disclosure, and pharmaceutically acceptable compositions thereof, are useful for treating various diseases, disorders, or conditions, including those described herein. In some embodiments, the condition, disorder, or illness is cancer. [Brief explanation of the drawings]

[0018] [Figure 1] Provided compounds are capable of recruiting antibodies to target cells. [Figure 2] The provided compounds are capable of recruiting antibodies to target cells and activating effector cells. [Figure 3] The compounds provided can kill target cells. [Figure 4] The provided compounds do not significantly deplete effector cells. Daratumumab 3ug / mL~0.1ug / mL. I-9 300nM~10nM. IvIG 10ug / mL. [Figure 5] The provided technique has low toxicity. A. Frequency of dead NK cells. B. Frequency of dead NK cells normalized to DMSO-treated control. The ARM of CD38 is I-17. [Figure 6] The provided technology can effectively kill cancer cells. A. Frequency of dead SUDHL-4 cells in NK-SUDHL-4 co-cultures. B. Frequency of dead SUDHL-4 cells in NK-SUDHL-4 co-cultures normalized to DMSO-treated controls. The ARM of CD38 is I-17. [Figure 7]The provided technique can reduce the number of plasma cells. The ARM of CD38 is I-17. [Figure 8] The provided techniques result in little to no unwanted NK cell fratricide. The ARM of CD38 is I-17. [Figure 9] The provided technique can effectively reduce the number of target cells. Without intending to be limited by theory, enumeration of CD38-expressing Daudi cells in the peritoneal cavity of SCID mice was performed as a readout of macrophage-mediated I-17-dependent phagocytosis. From left to right: control, IVIG 10 mg / mouse subcutaneously (sub-Q), I-17 1 mg / kg + IVIG (10 mg / mouse subcutaneously), I-17 10 mg / kg + IVIG (10 mg / mouse subcutaneously), I-17 30 mg / kg + IVIG (10 mg / mouse subcutaneously), and daratumumab. ***: P<0.001. [Figure 10] Activity of CIML NK cells frozen and harvested in combination with I-17 against MOLP-8 cells. From left to right: untreated, daratumumab, cryopreserved CIML NK I-17 added to the assay, and cryopreserved CIML NK with I-17. DETAILED DESCRIPTION OF THE INVENTION

[0019] 1. General Description of Specific Embodiments In some embodiments, the present disclosure provides an agent (e.g., an ARM) comprising a target binding moiety capable of binding to CD38. In some embodiments, the provided agent (e.g., an ARM) comprises a universal antibody binding moiety capable of binding to antibodies with different Fab structures. In some embodiments, the present disclosure provides an agent (e.g., an ARM) comprising an antibody binding moiety (e.g., an Fc region of an antibody) that binds to an antibody, wherein such binding of the antibody does not interfere with one or more immune activities of the antibody, such as interaction with an Fc receptor (e.g., CD16a), recruitment of effector cells such as NK cells (e.g., in the case of ADCC), macrophages (e.g., in the case of ADCP), etc. As will be appreciated by those skilled in the art, the provided technology (e.g., agents, compounds, compositions, methods) of the present disclosure can offer various advantages, for example, the provided technology can utilize antibodies with different Fab regions on the immune system to avoid or minimize the undesirable effects of antibody variation in patient populations, can induce and / or enhance immune activity against a target (e.g., killing target disease cells such as cancer cells), and / or is less toxic (e.g., less complement activation) than certain antibody therapeutics, resulting in significantly less depletion of normal cells that express CD38 (e.g., effector cells).

[0020] In some embodiments, the provided technology is useful for modulating immune activity, such as ADCC, ADCP, and combinations thereof, against targets (such as disease cells, foreign bodies, or entities) that include CD38. In some embodiments, the disclosed technology is useful for recruiting antibodies to cancer cells, particularly those that express CD38. In some embodiments, the provided technology is useful for modulating ADCC against target cells (e.g., disease cells such as cancer cells). In some embodiments, the provided technology is useful for modulating ADCP against target cells (e.g., disease cells such as cancer cells). In some embodiments, the provided agents are capable of inhibiting the activity of a protein. In some embodiments, the target binding moiety is an inhibitor moiety. In some embodiments, the target binding moiety is an enzyme inhibitor moiety.

[0021] In some embodiments, the present disclosure provides: an antibody binding moiety; a target binding moiety capable of binding to CD38; optionally a linker moiety; and wherein the antibody binding moieties are capable of binding to two or more antibodies having different Fab regions.

[0022] In some embodiments, the present disclosure provides: an antibody binding moiety; a target binding moiety capable of binding to CD38; optionally a linker moiety; and wherein the antibody binding moieties are capable of binding to two or more antibodies having different Fab regions.

[0023] In some embodiments, provided agents comprise two or more antibody binding moieties. In some embodiments, provided agents comprise two or more target binding moieties.

[0024] The antibody binding moiety can interact with any part of an antibody. In some embodiments, the antibody binding moiety binds to the Fc region of an antibody. In some embodiments, the antibody binding moiety binds to the conserved Fc region of an antibody. In some embodiments, the antibody binding moiety binds to the Fc region of an IgG antibody. As will be appreciated by those skilled in the art, a variety of antibody binding moieties, linkers, and target binding moieties can be utilized in accordance with the present disclosure. Among other things, as demonstrated in the Examples, in some embodiments, the present disclosure provides antibody binding moieties, linkers, and target binding moieties, and combinations thereof, which are particularly useful and effective for constructing ARM molecules to recruit antibodies to target cells and / or induce, generate, promote, and / or enhance the activity of the immune system against target cells (e.g., diseased cells such as cancer cells).

[0025] In some embodiments, the present disclosure provides antibody binding moieties and / or agents (e.g., compounds of various formulas described in this disclosure, ARM molecules of the present disclosure, etc.) that comprise an antibody binding moiety that can bind to an Fc region that binds to an Fc receptor (e.g., FcγRIIIa, CD16a, etc.). In some embodiments, the provided moieties and / or agents comprise an antibody binding moiety that binds to a complex comprising an Fc region and an Fc receptor. In some embodiments, the present disclosure provides a complex comprising the agent, The drug is an antibody binding moiety; a target binding moiety; and Optionally, a linker moiety, the Fc region, and and an Fc receptor.

[0026] In some embodiments, the antibody binding moiety is capable of binding to CD38 and / or the antibody binding moiety of the agent is capable of binding to two or more antibodies with different Fab regions.

[0027] In some embodiments, the Fc region is the Fc region of an endogenous antibody of the subject. In some embodiments, the Fc region is the Fc region of an exogenous antibody. In some embodiments, the Fc region is the Fc region of an administered drug. In some embodiments, the Fc receptor is on diseased cells in the subject. In some embodiments, the Fc receptor is on cancer cells in the subject.

[0028] In certain embodiments, the present disclosure provides a compound of formula I: [ka] or a pharmaceutically acceptable salt thereof, wherein: each of a and b independently represents 1 to 200; each ABT is independently an antibody binding moiety; L is a bivalent or polyvalent linker moiety connecting ABT and TBT; Each TBT is independently a target binding moiety.

[0029] In some embodiments, the ABT is a universal antibody binding moiety.

[0030] In some embodiments, the antibody binding moiety comprises one or more amino acid residues. In some embodiments, the antibody binding moiety is or comprises a peptide moiety. In some embodiments, the antibody binding moiety is or comprises a cyclic peptide moiety. In some embodiments, such antibody binding moieties comprise one or more naturally occurring amino acid residues. In some embodiments, such antibody binding moieties comprise one or more non-naturally occurring amino acid residues.

[0031] In some embodiments, the amino acid has the structure of formula AI: NH(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 -COOH, AI or a salt thereof, wherein R a1 , R a2 , R a3 each independently represents -L a -R', L a1 and L a2 Each of the a and Each L a are independently a covalent bond or C-C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy-, —O—, —S—, —SS-, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)N(R′)—, —C(O)S—, or —C(O)O—; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3-20 Alicyclic ring, C 6-20 an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1-30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently, taken together with that atom, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0032] In some embodiments, amino acid analogs are compounds in which the amino and / or carboxylic acid groups are independently replaced with an optionally substituted aliphatic or heteroaliphatic moiety. As will be appreciated by those skilled in the art, many amino acid analogs that mimic the structure, properties, and / or function of amino acids have been described in the art and can be utilized in accordance with the present disclosure.

[0033] In some embodiments, the antibody binding moiety is a cyclic peptide moiety. In some embodiments, the present disclosure provides a compound of formula Ia: [ka] or a salt thereof, wherein: each Xaa is independently a residue of an amino acid or amino acid analog; t is 0 to 50; z is 1 to 50; L is a linker moiety, TBT is the target binding moiety, Each R c independently, -L a -R', each of a and b independently represents 1 to 200; Each L a are independently a covalent bond or C-C 20 Aliphatic or C1-C with 1-5 heteroatoms 20heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy-, —O—, —S—, —SS-, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)N(R′)—, —C(O)S—, or —C(O)O—; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3-20 Alicyclic ring, C 6-20 an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1-30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently, taken together with that atom, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0034] In some embodiments, a is 1. In some embodiments, b is 1. In some embodiments, a is 1 and b is 1, and the compound of formula Ia is [ka] It has the following structure.

[0035] In some embodiments, each residue, e.g., Xaa, is independently a residue of an amino acid or amino acid analog, and the amino acid or amino acid analog is HL a1 -L a1 -C(R a2 )(R a3 )-L a2 -L a2 In some embodiments, the amino acid has the structure NH(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 In some embodiments, the amino acid analog has the structure HL a1 -L a1 -C(R a2 )(R a3 )-L a2 -L a2 In some embodiments, such amino acid analogs have the structure -H, or a salt thereof. a1- (wherein bonded to -H) is -N(R a1 )- (e.g., optionally substituted divalent C 1-6 In some embodiments, HL a1 -L a1 -In -L a1 -L a1 - is attached to -H through a non-nitrogen atom. a2 -L a2 In -H, -L a2 -L a2 - is not attached to -H through -C(O)O-. In some embodiments, each residue (e.g., each Xaa in Formula Ia) is independently a residue of an amino acid having the structure of Formula AI.

[0036] In some embodiments, each Xaa is independently -L a1 -L a1 -C(R a2 )(R a3 )-L a2 -L a2 In some embodiments, each Xaa independently has the structure -L aX1 -L a1 -C(R a2 )(R a3 )-L a2 -L aX2 -having the structure of L aX1 is an optionally substituted —NH—, an optionally substituted —CH—, —N(R a1 )-, or -S-, and L aX2 is an optionally substituted —NH—, an optionally substituted —CH—, —N(R a1 )-, or -S-, and each other variable is independently as described herein. In some embodiments, L aX1 is an optionally substituted —NH—, or —N(R a1 In some embodiments, L aX1 is an optionally substituted —CH—, or —S—. In some embodiments, L aX2 is an optionally substituted —NH—, an optionally substituted —CH—, —N(R a1)-, or -S-. In some embodiments, the optionally substituted -CH2- is -C(O)-. In some embodiments, the optionally substituted -CH2- is not -C(O)-. In some embodiments, L aX2 In some embodiments, each Xaa is independently -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 It has the structure -CO-.

[0037] In many embodiments, two or more residues (e.g., two or more Xaa residues) are linked together to form one or more ring structures. For example, various compounds in Table 1 include linked residues. The residues can optionally be joined at any suitable position by a linker (e.g., L T ) of an amino acid residue. For example, the linkage between two residues can be independently connected to each residue at the N-terminus, C-terminus, a point on the backbone, or a point on a side chain, etc. In some embodiments, more than one side chain of a residue can be connected, e.g., through a linkage between two residues of Formula Ia (e.g., R a2 or R a3 and another amino acid residue R a2 or R a3 ) optionally form a bridge together (e.g., in various compounds of Table 1), e.g., in some embodiments, two cysteine ​​residues form a -SS- bridge, as typically observed in natural proteins. In some embodiments, the bridge formed is b It has the structure of L b is, as described in this disclosure, L a In some embodiments, L b each end of which is independently connected to a backbone atom of the cyclic peptide (e.g., -(Xaa) of Formula Ia) z -) to a ring atom of the ring formed by L b includes an R group (e.g., L bwhere the methylene units of are replaced by -C(R)2- or -N(R)-, the R group is an R group attached to a backbone atom (e.g., R a1 , R a2 , R a3 and the like, when R) together with their intervening atoms form a ring. b is connected to the ring (e.g., -(Xaa) in Formula Ia) via the side chain of the amino acid residue (e.g., Xaa in Formula Ia) z In some embodiments, such side chains include amino groups or carboxylic acid groups. In some embodiments, L T is the L described herein b In some embodiments, the linkage (e.g., L b or L T ) connects a side chain to the N-terminus or C-terminus of a residue. In some embodiments, a linkage connects a side chain to an amino group of a residue. In some embodiments, a linkage connects a side chain to an α-amino group of a residue. In some embodiments, a linkage (e.g., L b or L T ) is -CH2-C(O)-. In some embodiments, -CH2- is attached to a side chain (e.g., attached to the -S- of a cysteine ​​residue) and -C(O)- is attached to an amino group (e.g., the alpha amino group of a residue). In some embodiments, the linkage (e.g., L b or L T ) is an optionally substituted —CH—S—CH—C(O)—NH—, where each terminus is attached to the alpha carbon of the residue. In some embodiments, —NH— is the alpha amino group of the residue (e.g., the alpha amino group of the N-terminal residue).

[0038] In some embodiments, [ka] is the antibody binding moiety ( [ka] binds to the antibody). In some embodiments, [ka] is a universal antibody binding moiety. In some embodiments, [ka] is a universal antibody binding moiety and can bind to antibodies with different Fab regions. [ka] is a universal antibody binding moiety and is capable of binding to the Fc region. In some embodiments, the antibody binding moiety (e.g., [ka] In some embodiments, the antibody binding moiety (e.g., a universal antibody binding moiety having the structure [ka] The antibody binding moiety has the structure [ka] In some embodiments, [ka] teeth, [ka] It has the following structure.

[0039] In certain embodiments, the present disclosure provides a compound of formula II: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 1 , R 3 , and R 5each independently is hydrogen or C 1-6 an optionally substituted group selected from an aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocycle, a phenyl, an 8-10 membered bicyclic aromatic carbocycle, a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1 and R 1’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle, or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or R 3 and R 3’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle, or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or R attached to the same carbon atom 5 Groups and R 5’ groups, together with their intervening carbon atoms, form a 3- to 8-membered optionally substituted saturated or partially unsaturated spirocyclic carbocycle, or a 3- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or The Two R's 5 The groups, optionally together with their intervening atoms, are C 1-10wherein 1 to 3 methylene units of the chain are independently and optionally selected from -S-, -SS-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, or -Cy 1 -, and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1’ , R 3’ , and R 5’ each independently represents hydrogen or an optionally substituted C 1-3 is aliphatic, R 2 , R 4 , and R 6 each independently represents hydrogen or an optionally substituted C 1-4 is aliphatic, or R 2 and R 1 optionally taken together with their intervening atoms, form an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 4 and R 3 optionally taken together with their intervening atoms, form a 4-8 membered, optionally substituted, saturated or partially unsaturated, monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or R 6 group and its adjacent R 5 groups optionally taken together with their intervening atoms form a 4-8 membered, optionally substituted, saturated or partially unsaturated, monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; L 1 teeth, [ka] is a trivalent linker moiety connecting L 2 is a covalent bond or an optionally substituted C 1-30 wherein 1 to 10 methylene units of the chain are independently and optionally selected from -S-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, [ka] or -Cy 1 -, and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; TBT is the target binding moiety, Each of m and n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0040] In some embodiments, the antibody binding moiety is or comprises a peptide moiety. In some embodiments, the present disclosure provides a compound having the structure of Formula Ib: [ka] or a salt thereof, wherein: each Xaa is independently a residue of an amino acid or amino acid analog; each z is independently 1 to 50; each L is independently a linker moiety; TBT is the target binding moiety, Each R c independently, -L a -R', Each of a1 and a2 is independently 0 or 1, and at least one of a1 and a2 is not 0; each of a and b independently represents 1 to 200; Each L aare independently a covalent bond or C-C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy-, —O—, —S—, —SS-, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)N(R′)—, —C(O)S—, or —C(O)O—; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3-20 Alicyclic ring, C 6-20 an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1-30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently, taken together with that atom, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0041] In some embodiments, a1 is 1. In some embodiments, a2 is 1. In some embodiments, b is 1. In some embodiments, the compound of formula Ib is [ka] In some embodiments, the compound of formula Ib has the structure: [ka] In some embodiments, the compound of formula Ib has the structure: [ka] In some embodiments, the compound of formula Ib has the structure: [ka] It has the following structure.

[0042] In some embodiments, each residue (e.g., each Xaa of Formula Ia, Ib, etc.) is independently a residue of an amino acid having the structure of Formula AI. In some embodiments, each Xaa is independently -N(R a1 )-L a1 -C(R a2)(R a3 )-L a2 In some embodiments, more than one side chain of an amino acid residue, e.g., a side chain of a compound of Formula Ia (e.g., R a2 or R a3 and another amino acid residue R a2 or R a3 ) optionally form a bridge together (e.g., various compounds in Table 1); for example, in some embodiments, two cysteine ​​residues form a -SS- bridge, as typically observed in natural proteins. In some embodiments, the bridge formed is b It has the structure of L b is, as described in this disclosure, L a In some embodiments, L b each end independently connects to a backbone atom of the cyclic peptide (e.g., -(Xaa) of Formula Ia) z -) to a ring atom of the ring formed by L b includes an R group (e.g., L b where the methylene units of are replaced by -C(R)2- or -N(R)-, the R group is an R group attached to a backbone atom (e.g., R a1 , R a2 , R a3 and the like, when R) together with their intervening atoms form a ring. b is connected to the ring (e.g., -(Xaa) in Formula Ib) via the side chain of an amino acid residue (e.g., Xaa in Formula Ia) z -) In some embodiments, such side chains comprise an amino group or a carboxylic acid group.

[0043] In some embodiments, R c -(Xaa)z- is an antibody binding moiety (R c -(Xaa)zH binds to the antibody). In some embodiments, R c -(Xaa)z- is a universal antibody binding moiety. In some embodiments, R c-(Xaa)z- is a universal antibody binding moiety and can bind to antibodies with different Fab regions. In some embodiments, R c -(Xaa)z- is a universal antibody binding moiety and is capable of binding to the Fc region. In some embodiments, the antibody binding moiety (e.g., R c A universal antibody binding moiety having the structure -(Xaa)z-) can bind to an Fc region that binds to an Fc receptor. In some embodiments, R c -(Xaa)z- is [ka] In some embodiments, R c -(Xaa)zL- is [ka] It has the following structure.

[0044] In certain embodiments, the present disclosure provides a compound of formula III: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 7 each independently is hydrogen or C 1-6 an optionally substituted group selected from an aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocycle, a phenyl, an 8-10 membered bicyclic aromatic carbocycle, a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R attached to the same carbon atom 7 Groups and R 7’groups, together with their intervening carbon atoms, form a 3- to 8-membered, optionally substituted, saturated or partially unsaturated spirocyclic carbocycle, or a 3- to 8-membered, optionally substituted, saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 7’ each independently represents hydrogen or an optionally substituted C 1-3 is aliphatic, R 8 each independently represents hydrogen or an optionally substituted C 1-4 is aliphatic, or R 8 group and its adjacent R 7 groups optionally taken together with their intervening atoms form a 4-8 membered, optionally substituted, saturated or partially unsaturated, monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 9 is hydrogen or optionally substituted C 1-3 Aliphatic or -C(O)-(optionally substituted C 1-3 aliphatic), L 3 TBT and [ka] is a bivalent linker moiety connecting TBT is the target binding moiety, o is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0045] 2.Definition The compounds of the present disclosure include those compounds generally described herein and are further exemplified by the classes, subclasses, and species disclosed herein. As used herein, the following definitions apply unless otherwise indicated. For purposes of this disclosure, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Furthermore, general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry", 5th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001.

[0046] As used herein, unless otherwise clear from the context, (i) the term "a" or "an" may be understood to mean "at least one," (ii) the term "or" may be understood to mean "and / or," (iii) the terms "comprising," "comprise," "including" (whether or not used in conjunction with "limited to"), and "include" (whether or not used in conjunction with "limited to") may be understood to encompass the listed components or steps, whether presented by themselves or presented with one or more additional components or steps, (iv) the term "another" may be understood to mean at least an additional / second one or more, (v) the terms "about" and "approximately" may be understood to allow for standard deviation, as understood by one of ordinary skill in the art, and (vi) when ranges are provided, the endpoints are included. Unless otherwise specified, the compounds described herein may be provided and / or utilized in the form of salts, particularly pharmaceutically acceptable salts.

[0047] Aliphatic: As used herein, "aliphatic" refers to a linear (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more units of unsaturation, or a substituted or unsubstituted monocyclic, bicyclic, or polycyclic hydrocarbon ring that is fully saturated or contains one or more units of unsaturation (but is not aromatic), or a combination thereof. In some embodiments, an aliphatic group contains 1-50 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1-20 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-10 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-9 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-8 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-7 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-6 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1, 2, 3, or 4 aliphatic carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups, and hybrids thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0048] Alkenyl: As used herein, the term "alkenyl" refers to an aliphatic group, as defined herein, having one or more double bonds.

[0049] Alkyl: As used herein, the term "alkyl" is given its ordinary meaning in the art and may include saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. In some embodiments, an alkyl has 1-100 carbon atoms. In certain embodiments, a straight-chain or branched-chain alkyl has about 1-20 carbon atoms in its backbone (e.g., C1-C6 for a straight chain).20 , C2-C for branched chains 20 ), or about 1-10 carbon atoms. In some embodiments, cycloalkyl rings have from about 3-10 carbon atoms in their ring structure, and such rings may be monocyclic, bicyclic or polycyclic, or have about 5, 6 or 7 carbons in the ring structure. In some embodiments, alkyl groups can be lower alkyl groups, which lower alkyl groups have from 1-4 carbon atoms (e.g., C1-C4 for a straight chain lower alkyl).

[0050] Alkynyl: As used herein, the term "alkynyl" refers to an aliphatic group, as defined herein, having one or more triple bonds.

[0051] Aryl: As used herein, the term "aryl," whether used alone or as part of a larger moiety such as "aralkyl," "aralkoxy," or "aryloxyalkyl," refers to a monocyclic, bicyclic, or polycyclic ring system having a total of 5 to 30 ring members, wherein at least one ring in the system is aromatic. In some embodiments, an aryl group is a monocyclic, bicyclic, or polycyclic ring system having a total of 5 to 14 ring members, wherein at least one ring in the system is aromatic, and each ring in the system contains 3 to 7 ring members. In some embodiments, an aryl group is a biaryl group. The term "aryl" may be used interchangeably with the term "aryl ring." In certain embodiments of the present disclosure, "aryl" refers to an aromatic ring system, including, but not limited to, phenyl, biphenyl, naphthyl, binaphthyl, anthracyl, and the like, which may bear one or more substituents. Also included within the scope of the term "aryl" as used herein are groups in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthymidyl, phenanthridinyl, or tetrahydronaphthyl.

[0052] Alicyclic: The terms "alicyclic," "carbocyclic," "carbocyclyl," "carbocyclic radical," and "carbocycle" are used interchangeably and, as used herein, unless otherwise specified, refer to a saturated or partially unsaturated, but non-aromatic, cyclic aliphatic monocyclic, bicyclic, or polycyclic ring system described herein having 3 to 30 ring members. Alicyclic groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, norbornyl, adamantyl, and cyclooctadienyl. In some embodiments, an alicyclic group has 3 to 6 carbons. In some embodiments, an alicyclic group is saturated and is a cycloalkyl. The term "alicyclic" may also include an aliphatic ring fused to one or more aromatic or non-aromatic rings, such as decahydronaphthyl or tetrahydronaphthyl. In some embodiments, an alicyclic group is bicyclic. In some embodiments, an alicyclic group is tricyclic. In some embodiments, an alicyclic group is polycyclic. In some embodiments, an "alicyclic" refers to a C3-C6 monocyclic hydrocarbon having a single point of attachment to the rest of the molecule, or a C8-C6 monocyclic hydrocarbon having a single point of attachment to the rest of the molecule, which is fully saturated or contains one or more units of unsaturation, but is not aromatic. 10 Bicyclic or polycyclic hydrocarbons, or C9-C, which are fully saturated or contain one or more units of unsaturation but are not aromatic, with a single point of attachment to the rest of the molecule 16 Refers to polycyclic hydrocarbons.

[0053] Dosing regimen: As used herein, "dosing regimen" or "therapeutic regimen" refers to a series of unit doses (typically two or more) administered individually to a subject, typically separated by a period of time. In some embodiments, a given therapeutic agent has a recommended dosing regimen that may involve one or more doses. In some embodiments, a dosing regimen includes multiple doses, each of which is separated from the other by a period of equal length; in some embodiments, a dosing regimen includes multiple doses and at least two different periods separating the individual doses. In some embodiments, all doses within a dosing regimen are the same unit dose. In some embodiments, different doses within a dosing regimen are different amounts. In some embodiments, a dosing regimen includes a first administration of a first dose, followed by one or more additional administrations of a second dose that is different from the first dose. In some embodiments, a dosing regimen includes a first administration of a first dose, followed by one or more additional administrations of a second dose that is the same as the first dose.

[0054] Heteroaliphatic: The term "heteroaliphatic," as used herein, is given its ordinary meaning in the art and refers to an aliphatic group, as described herein, in which one or more carbon atoms are independently replaced with one or more heteroatoms (e.g., oxygen, nitrogen, sulfur, silicon, phosphorus, etc.). In some embodiments, one or more units selected from C, CH, CH, and CH are independently replaced with one or more heteroatoms (including oxidized and / or substituted forms thereof). In some embodiments, a heteroaliphatic group is a heteroalkyl. In some embodiments, a heteroaliphatic group is a heteroalkenyl.

[0055] Heteroalkyl: The term "heteroalkyl," as used herein, is given its ordinary meaning in the art and refers to an alkyl group, as described herein, in which one or more carbon atoms are independently replaced with one or more heteroatoms (e.g., oxygen, nitrogen, sulfur, silicon, phosphorus, etc.). Examples of heteroalkyl groups include, but are not limited to, alkoxy, poly(ethylene glycol)-, alkyl-substituted amino, tetrahydrofuranyl, piperidinyl, morpholinyl, and the like.

[0056] Heteroaryl: As used herein, the terms "heteroaryl" and "heteroal-," when used alone or as part of a larger moiety (e.g., "heteroaralkyl" or "heteroaralkoxy"), refer to a monocyclic, bicyclic, or polycyclic ring system having a total of 5 to 30 ring members, in which at least one ring in the system is aromatic and at least one aromatic ring atom is a heteroatom. In some embodiments, heteroaryl groups are groups having 5 to 10 ring atoms (i.e., monocyclic, bicyclic, or polycyclic), and in some embodiments, 5, 6, 9, or 10 ring atoms. In some embodiments, heteroaryl groups have 6, 10, or 14 pi electrons shared in the cyclic array, and have 1 to 5 heteroatoms in addition to the carbon atoms. Heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. In some embodiments, heteroaryl is a heteroaryl group such as bipyridyl. As used herein, the terms "heteroaryl" and "heteroar-" also include groups in which a heteroaromatic ring is fused to one or more aryl rings, alicyclic rings, or heterocyclyl rings, and the radical or point of attachment is on the heteroaromatic ring. Non-limiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. Heteroaryl groups can be monocyclic, bicyclic, or polycyclic.The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroaromatic," any of which include rings that are optionally substituted. The term "heteroaralkyl" refers to an alkyl group substituted by a heteroaryl group, where the alkyl and heteroaryl portions independently are optionally substituted.

[0057] Heteroatom: As used herein, the term "heteroatom" refers to an atom that is not carbon or hydrogen. In some embodiments, the heteroatom is boron, oxygen, sulfur, nitrogen, phosphorus, or silicon (various forms of such atoms, e.g., oxidized forms (e.g., nitrogen, sulfur, phosphorus, or silicon), quaternized forms of basic nitrogens, or heterocycles (e.g., N in 3,4-dihydro-2H-pyrrolyl), NH (in pyrrolidinyl), or NR + (including substitutable nitrogen in N-substituted pyrrolidinyl, etc.). In some embodiments, the heteroatom is oxygen, sulfur, or nitrogen.

[0058] Heterocycle: As used herein, the terms "heterocycle," "heterocyclyl," "heterocyclic radical," and "heterocycle" are used interchangeably and refer to a monocyclic, bicyclic, or polycyclic ring moiety (e.g., a 3- to 30-membered ring) that is saturated or partially unsaturated and has one or more heteroatom ring atoms. In some embodiments, a heterocyclyl group is a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic moiety that is saturated or partially unsaturated and has, in addition to carbon atoms, one or more, preferably 1 to 4, heteroatoms as defined above. When used in reference to a ring atom of a heterocycle, the term "nitrogen" includes substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0 to 3 heteroatoms selected from oxygen, sulfur, and nitrogen, the nitrogen can be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or . +It may be NR (as in N-substituted pyrrolidinyl). A heterocycle can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure, and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, but are not limited to, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms "heterocycle," "heterocyclyl," "heterocyclyl ring," "heterocyclic group," "heterocyclic moiety," and "heterocyclic radical" are used interchangeably herein and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or alicyclic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. Heterocyclyl groups can be monocyclic, bicyclic, or polycyclic. The term "heterocyclylalkyl" refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions are independently optionally substituted.

[0059] Lower alkyl: The term "lower alkyl" refers to a C 1-4 It refers to a straight-chain or branched alkyl group. Examples of lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0060] Lower haloalkyl: The term "lower haloalkyl" refers to a C alkyl group substituted with one or more halogen atoms. 1-4 Refers to a straight or branched chain alkyl group.

[0061] Optionally substituted: As described herein, compounds of the present disclosure may contain optionally substituted and / or substituted moieties. In general, the term "substituted," whether preceded by the term "optionally," means that one or more hydrogens of the specified moiety are replaced with a suitable substituent. Unless otherwise indicated, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and if more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituents may be the same or different at all positions. In some embodiments, an optionally substituted group is unsubstituted. Combinations of substituents envisioned by the present disclosure are preferably those that result in the formation of stable or chemically feasible compounds. As used herein, the term "stable" refers to compounds that are substantially unchanged when subjected to conditions that allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more purposes disclosed herein. Specific substituents are described below.

[0062] Suitable monovalent substituents on a substitutable atom (e.g., a suitable carbon atom) are independently halogen, —(CH) 0-4 R^, -(CH2) 0-4 OR^, -O(CH2) 0-4 R°, -O-(CH2) 0-4 C(O)OR°, -(CH2) 0-4 CH(OR^)2, -(CH2) 0-4 Ph (which may be substituted with R), -(CH) 0-4 O(CH2) 0-1 Ph (which may be substituted with R°), -CH=CHPh (which may be substituted with R°), -(CH) 0-4 O(CH2) 0-1 -pyridyl (which may be substituted with R), -NO2, -CN, -N3, -(CH2) 0-4 N(R^)2, -(CH2) 0-4 N(R^)C(O)R^, -N(R^)C(S)R^, -(CH2) 0-4N(R^)C(O)NR^2, -N(R^)C(S)NR^2, -(CH2) 0-4 N(R^)C(O)OR^, -N(R^)N(R^)C(O)R^, -N(R^)N(R^)C(O)NR^2, -N(R^)N(R^)C(O)OR^, -(CH2) 0-4 C(O)R^, -C(S)R^, -(CH2) 0-4 C(O)OR^, -(CH2) 0-4 C(O)SR^, -(CH2) 0-4 C(O)OSiR^3, -(CH2) 0-4 OC(O)R^, -OC(O)(CH2) 0-4 SR^, -SC(S)SR^, -(CH2) 0-4 SC(O)R^, -(CH2) 0-4 C(O)NR^2, -C(S)NR^2, -C(S)SR^, -(CH2) 0-4 OC(O)NR^2, -C(O)N(OR^)R^, -C(O)C(O)R^, -C(O)CH2C(O)R^, -C(NOR^)R^, -(CH2) 0-4 SSR^, -(CH2) 0-4 S(O)2R^, -(CH2) 0-4 S(O)2OR^, -(CH2) 0-4 OS(O)2R^, -S(O)2NR^2, -(CH2) 0-4 S(O)R^, -N(R^)S(O)2NR^2, -N(R^)S(O)2R^, -N(OR^)R^, -C(NH)NR^2, -Si(R^)3, -OSi(R^)3, -B(R^)2, -OB(R^)2, -OB(OR^)2, -P(R^)2, -P(OR^)2, -P(R^)(OR^), -OP(R^)2, -OP(OR^)2, -OP(R^)(OR^), -P(O)(R^)2, -P(O)(OR^)2, -OP(O)(R^)2, -OP(O)(OR^)2, -OP(O)(OR^)(SR^), -SP(O)(R^)2, -SP(O)(OR^)2, -N(R^)P(O)(R^)2, -N(R^)P(O)(OR^)2, -P(R^)2[B(R^)3], -P(OR^)2[B(R^)3], -OP(R^)2[B(R^)3], -OP(OR^)2[B(R^)3], -(C 1-4 linear or branched alkylene)O-N(R^)2, or -(C1-4 linear or branched alkylene)C(O)ON(R^)2, where each R^ may be substituted as defined herein and independently represents hydrogen, C 1-20 Aliphatic, C with 1 to 5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus 1-20 Heteroaliphatic, -CH2-(C 6-14 aryl), -O(CH2) 0-1 (C 6-14 aryl), -CH2 (a 5-14 membered heteroaryl ring), a 5-20 membered mono-, bi-, or polycyclic saturated, partially unsaturated, or aryl ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus; or, notwithstanding the above definitions, two independent occurrences of R^ taken together with their intervening atoms form a 5-20 membered mono-, bi-, or polycyclic saturated, partially unsaturated, or aryl ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, sulfur, silicon, and phosphorus, which may be substituted as defined below.

[0063] Suitable monovalent substituents on R^ (or the ring formed by two independent occurrences of R^ taken together with their intervening atoms) are independently halogen, -(CH2) 0-2 R ● ,-(Halo R ● ), -(CH2) 0-2 OH, -(CH2) 0-2 OR ● , -(CH2) 0-2 CH(OR ● )2, -O(HaloR ● ), -CN, -N3, -(CH2) 0-2 C(O)R ● , -(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR ● , -(CH2) 0-2 SR ● , -(CH2) 0-2 SH, -(CH2) 0-2 NH2, -(CH2) 0-2 NHR ● , -(CH2)0-2 NR ● 2, -NO2, -SiR ● 3. -OSiR ● 3. -C(O)SR ● , -(C 1-4 Linear or branched alkylene)C(O)OR ● , or -SSR ● Here, each R ● is unsubstituted or, if preceded by "halo", is substituted only with one or more halogens, and independently represents C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 and a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Suitable divalent substituents on a saturated carbon atom of R include =0 and =S.

[0064] For example, suitable divalent substituents on suitable carbon atoms are, independently, the following: =O, =S, =NNR * 2, =NNHC(O)R * , =NNHC(O)OR * , =NNHS(O)2R * , =NR * , =NOR * , -O(C(R * 2)) 2-3 O-, or -S(C(R * 2)) 2-3 S-, where R * Each independent occurrence of may be substituted as defined below with hydrogen, C 1-6 aliphatic and unsubstituted 5-6 membered saturated, partially unsaturated, or aryl rings having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Preferred divalent substituents attached to a vicinal substitutable carbon of an "optionally substituted" group include -O(CR * 2) 2-3 O-, where R * Each independent occurrence of may be substituted as defined below with hydrogen, C 1-6Selected from aliphatic and unsubstituted 5-6 membered saturated, partially unsaturated, and aryl rings having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0065] R * Suitable substituents on the aliphatic group are independently halogen, —R ● ,-(Halo R ● ), -OH, -OR ● , -O(HaloR ● ), -CN, -C(O)OH, -C(O)OR ● , -NH2, -NHR ● , -NR ● 2, or -NO2, where each R ● is unsubstituted or, if preceded by "halo", is substituted only with one or more halogens, and independently represents C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0066] In some embodiments, suitable substituents on a substitutable nitrogen are independently —R † , -NR † 2. -C(O)R † , -C(O)OR † , -C(O)C(O)R † , -C(O)CHC(O)R † , -S(O)2R † , -S(O)NR † 2. -C(S)NR † 2. -C(NH)NR † 2, or -N(R † )S(O)2R † Here, each R † are independently hydrogen, C which may be substituted as defined below 1-6 an aliphatic, unsubstituted -OPh, or unsubstituted 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or two independent R †together with their intervening atoms form an unsubstituted 3-12 membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0067] R † Suitable substituents on the aliphatic group are independently halogen, —R ● ,-(Halo R ● ), -OH, -OR ● , -O(HaloR ● ), -CN, -C(O)OH, -C(O)OR ● , -NH2, -NHR ● , -NR ● 2, or -NO2, where each R ● is unsubstituted or, if preceded by "halo", is substituted only with one or more halogens, and independently represents C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0068] Partially unsaturated: As used herein, the term "partially unsaturated" refers to a ring moiety that includes at least one double or triple bond. The term "partially unsaturated" is intended to encompass rings with multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as defined herein.

[0069] Pharmaceutical composition: As used herein, the term "pharmaceutical composition" refers to an active agent formulated with one or more pharmaceutically acceptable carriers. In some embodiments, the active agent is present in a unit dose suitable for administration in a treatment regimen that exhibits a statistically significant probability of achieving a predetermined therapeutic effect when administered to a relevant population. In some embodiments, pharmaceutical compositions may be specially formulated for administration in solid or liquid form, including those adapted for oral administration (e.g., drenches (aqueous or non-aqueous solutions or suspensions), tablets (e.g., buccal, sublingual, and those intended for systemic absorption), boluses, powders, granules, pastes, pastes for application to the tongue), parenteral administration (e.g., as sterile solutions or suspensions, or sustained release formulations, e.g., by subcutaneous, intramuscular, intravenous, or epidural injection), topical application (e.g., as a cream, ointment, or controlled-release patch or spray applied to the skin, lungs, or oral cavity), vaginal or rectal (e.g., as a pessary, cream, or foam), sublingual, ocular, transdermal, or intranasal, pulmonary, and other mucosal surfaces.

[0070] Pharmaceutically acceptable: As used herein, the phrase "pharmaceutically acceptable" refers to compounds, materials, compositions and / or dosage forms that are pharmaceutically acceptable, within the scope of sound medical judgment, and commensurate with a reasonable benefit / risk ratio, and suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication.

[0071] Pharmaceutically acceptable carrier: As used herein, the term "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulant, that is involved in carrying or transporting a compound of interest from one organ or part of the body to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include sugars (such as lactose, glucose, and sucrose), starches (such as corn starch and potato starch), cellulose and its derivatives (such as sodium carboxymethylcellulose, ethyl cellulose, and cellulose acetate), powdered tragacanth, malt, gelatin, talc, excipients (such as cocoa butter and suppository waxes), oils (such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil), glycols (such as propylene glycol), polyols (such as glycerin, sorbitol, mannitol, and polyethylene glycol), esters (such as ethyl oleate and ethyl laurate), agar, buffers (such as magnesium hydroxide and aluminum hydroxide), alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, pH buffered solutions, polyesters, polycarbonates, and / or polyanhydrides, and other non-toxic compatible substances used in pharmaceutical formulations.

[0072] Pharmaceutically acceptable salts: As used herein, the term "pharmaceutically acceptable salts" refers to salts of such compounds that are suitable for use in pharmaceutical contexts, i.e., salts that are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, within the scope of sound medical judgment and commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66:1-19 (1977). In some embodiments, pharmaceutically acceptable salts include, but are not limited to, non-toxic acid addition salts of amino groups formed with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid), or organic acids (e.g., acetic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid), or by using other methods used in the art (e.g., ion exchange). In some embodiments, pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, or the like. These include, but are not limited to, bionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, and the like.In some embodiments, provided compounds contain one or more acidic groups, and pharmaceutically acceptable salts are alkali metal salts, alkaline earth metal salts, or ammonium salts (e.g., ammonium salts of N(R)3, where each R is independently defined and described in this disclosure). Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. In some embodiments, the pharmaceutically acceptable salt is a sodium salt. In some embodiments, the pharmaceutically acceptable salt is a potassium salt. In some embodiments, the pharmaceutically acceptable salt is a calcium salt. In some embodiments, pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations, formed, where appropriate, using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, alkyls having 1 to 6 carbon atoms, sulfonates, and arylsulfonates. In some embodiments, provided compounds contain two or more acidic groups. In some embodiments, pharmaceutically acceptable salts of such compounds, or salts in general, contain two or more cations, which may be the same or different. In some embodiments, in a pharmaceutically acceptable salt (or salt in general), all ionizable hydrogens of an acidic group (e.g., in an aqueous solution having a pKa of about 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 or less, in some embodiments, a pKa of about 7 or less, in some embodiments, about 6 or less, in some embodiments, about 5 or less, in some embodiments, about 4 or less, and in some embodiments, about 3 or less) are replaced with a cation.

[0073] Protecting group: The term "protecting group" as used herein is well known in the art and includes those described in detail in Protecting Groups in Organic Synthesis, T.W. Greene and P.G.M. Buts, 3rd edition, John Wiley & Sons, 1999 (incorporated herein by reference in its entirety). It also includes protecting groups specifically adapted for nucleoside and nucleotide chemistry described in Current Protocols in Nucleic Acid Chemistry, edited by Serge L. Beaucage et al. 06 / 2012 (incorporated herein by reference in its entirety, Chapter 2). Suitable amino protecting groups include methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-methyl- ... -phenylethyl carbamate (hZ), 1-(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2'-,4'-pyridyl)ethyl carbamate (Pyoc), 2-(N,N-dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropyl allyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyl dithiocarbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p- Nitobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3-dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4-dimethylthio Phenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2-triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m-chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5-benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl Carbamates, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, phenothiazinyl-(10)-carbonyl derivatives, N'-p-toluenesulfonylaminocarbonyl derivatives, N'-phenylaminothiocarbonyl derivatives, t-amyl carbamate, S-benzylthiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2-Dimethoxycarbonylvinylcarbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N-dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2-pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborin carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p'-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methyl 1-methyl-1-cyclohexyl carbamate, 1-methyl-1-cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl-1-(p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t-butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, 2,4,6-trimethylbenzyl Carbamates, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivatives, benzamide, p-phenylbenzamide, o-nitrophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N'-dithiobenzyloxycarbonylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o-nitrophenoxy)acetamide o-(o-phenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o-phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o-nitrocinnamide, N-acetylmethionine derivatives, o-nitrobenzamide, o-(benzoyloxymethyl)benzamide, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4-Tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5-triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl)amine, quaternary Ammonium salts, N-benzylamine, N-di(4-methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N'-oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, Np-methoximethane N-benzylideneamine, N-diphenylmethyleneamine, N-[(2-pyridyl)mesityl]methyleneamine, N-(N',N'-dimethylaminomethylene)amine, N,N'-isopropylidenediamine, Np-nitrobenzylideneamine, N-salicylideneamine, N-5-chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N-cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivatives, N-diphenylboron Phosphoric acid derivatives, N-[phenyl(pentacarbonylchromium or tungsten)carbonyl]amine, N-copper chelate, N-zinc chelate, N-nitramine, N-nitrosamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidate, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4-Dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, 3-nitropyridine sulfenamide (Npys), p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte) , 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4',8'-dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide.

[0074] Suitable protected carboxylic acids further include, but are not limited to, silyl-protected, alkyl-protected, alkenyl-protected, aryl-protected, and arylalkyl-protected carboxylic acids. Examples of suitable silyl groups include trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triisopropylsilyl, and the like. Examples of suitable alkyl groups include methyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, trityl, t-butyl, and tetrahydropyran-2-yl. Examples of suitable alkenyl groups include allyl. Examples of suitable aryl groups include optionally substituted phenyl, biphenyl, or naphthyl. Examples of suitable arylalkyl groups include optionally substituted benzyl (e.g., p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl, O-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl), and 2- and 4-picolyl.

[0075] Suitable hydroxyl protecting groups include methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl ( MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2-(trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]phenyl ]-4-Methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trimethyl- methylethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N-oxide, diphenylmethyl, p,p'-Dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α-naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p-methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4'-bromophenacyloxyphenyl)diphenylmethyl, 4,4',4''-tris(4,5-dichlorophthalimidophenyl)methyl, 4,4',4''-tris(levulinoyloxyphenyl)methyl, 4,4',4''-tris(benzoyloxyphenyl)methyl methyl, 3-(imidazol-1-yl)bis(4',4''-dimethoxyphenyl)methyl, 1,1-bis(4-methoxyphenyl)-1'-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10-oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxide, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl silyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate Acetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyl dithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), alkyl ethyl carbonate, alkyl 2,2,2-Trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl)ethyl carbonate (Psec), 2-(triphenylphosphonio)ethyl carbonate (Peoc), alkyl isobutyl carbonate, alkyl vinyl carbonate, alkyl allyl carbonate, alkyl p-nitrophenyl carbonate, alkyl benzyl carbonate, alkyl p-methoxybenzyl carbonate, alkyl 3,4-dimethoxybenzyl carbonate, alkyl o-nitrobenzyl carbonate, alkyl p-nitrobenzyl carbonate, alkyl S-benzylthiocarbonate, 4-ethoxy-1-naphthyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2-formyl Benzene sulfonate, 2-(methylthiomethoxy)ethyl, 4-(methylthiomethoxy)butyrate, 2-(methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoic acid nitrate, (E)-2-methyl-2-butenoate, o-(methoxycarbonyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N',N'-tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). When protecting 1,2-diols or 1,3-diols, the protecting groups include methylene acetal, ethylidene acetal, 1-t-butylethylidene ketal, 1-phenylethylidene ketal, (4-methoxyphenyl)ethylidene acetal, 2,2,2-trichloroethylidene acetal, acetonide, cyclopentylidene ketal, cyclohexylidene ketal, cycloheptylidene ketal, benzylidene acetal, p-methoxybenzylidene acetal, 2,4-Dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene acetal, 2-nitrobenzylidene acetal, methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene orthoester, 1-methoxyethylidene orthoester, 1-ethoxyethylidene orthoester, 1,2-dimethoxyethylidene orthoester, α-methoxybenzylidene orthoester, 1-(N,N-dimethylamino)ethoxymethyl Examples of suitable siloxanes include butylidene derivatives, α-(N,N'-dimethylamino)benzylidene derivatives, 2-oxacyclopentylidene orthoesters, di-t-butylsilylene groups (DTBS), 1,3-(1,1,3,3-tetraisopropyldisiloxanylidene) derivatives (TIPDS), tetra-t-butoxydisiloxane-1,3-diylidene derivatives (TBDS), cyclic carbonates, cyclic boronates, ethyl boronate, and phenyl boronate.

[0076] In some embodiments, the hydroxyl protecting group is acetyl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, benzoyl, p-phenylbenzoyl, 2,6-dichlorobenzyl, diphenylmethyl, p-nitrobenzyl, triphenylmethyl(trityl), 4,4′-dimethoxytrityl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, triisopropylsilyl, benzoylformate, chloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl, 9-fluorenylmethylcarbonate, mesylate, tosylate, triflate, trityl, monomethoxytrityl (MMTr), 4,4′-dimethoxytrityl, (DM ... Tr) and 4,4',4''-trimethoxytrityl (TMTr), 2-cyanoethyl (CE or Cne), 2-(trimethylsilyl)ethyl (TSE), 2-(2-nitrophenyl)ethyl, 2-(4-cyanophenyl)ethyl, 2-(4-nitrophenyl)ethyl (NPE), 2-(4-nitrophenylsulfonyl)ethyl, 3,5-dichlorophenyl, 2,4-dimethylphenyl, 2-nitrophenyl, 4-nitrophenyl, 2,4,6-trimethylphenyl, 2-(2-nitrophenyl)ethyl, butylthiocarbonyl, 4,4',4''-tris(benzoyloxy)trityl, diphenylcarbamoyl, levulinyl, 2-(dibromomethyl)benzoyl (Dbmb), 2-(isopropylthiomethoxymethyl)benzoyl (Ptmt), 9-phenylxanthin-9-yl (pixyl), or 9-(p-methoxyphenyl)xanthin-9-yl (MOX). In some embodiments, each of the hydroxyl protecting groups is independently selected from acetyl, benzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, and 4,4'-dimethoxytrityl. In some embodiments, the hydroxyl protecting groups are selected from the group consisting of trityl, monomethoxytrityl, and 4,4'-dimethoxytrityl groups.In some embodiments, the phosphorus-linked protecting group is a group that is linked to a phosphorus bond (e.g., an internucleotide bond) throughout oligonucleotide synthesis. In some embodiments, the protecting group is linked to the sulfur atom of a phosphorothioate group. In some embodiments, the protecting group is linked to the oxygen atom of an internucleotide phosphorothioate bond. In some embodiments, the protecting group is linked to the oxygen atom of an internucleotide phosphate bond. In some embodiments, the protecting group is 2-cyanoethyl (CE or Cne), 2-trimethylsilylethyl, 2-nitroethyl, 2-sulfonylethyl, methyl, benzyl, o-nitrobenzyl, 2-(p-nitrophenyl)ethyl (NPE or Npe), 2-phenylethyl, 3-(N-tert-butylcarboxamido)-1-propyl, 4-oxopentyl, 4-methylthio-1-butyl, 2-cyano-1,1-dimethylethyl, 4-N-methylaminobutyl, 3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, 2-(N-formyl,N-methyl)aminoethyl, or 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl.

[0077] Subject: As used herein, the term "subject" refers to any organism to which a compound or composition is administered in accordance with the present disclosure, e.g., for experimental, diagnostic, prophylactic, and / or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and humans, insects, parasites, etc.) and plants. In some embodiments, the subject is a human. In some embodiments, the subject may be suffering from and / or susceptible to a disease, disorder, and / or condition.

[0078] Substantially: As used herein, the term "substantially" refers to the qualitative state of exhibiting all, or nearly all, extent or degree of a desired characteristic or property. Those skilled in the art will understand that biological and chemical phenomena rarely, if ever, reach and / or progress to perfection or achieve or avoid absolute results. Thus, the term "substantially" is used herein to capture the potential lack of perfection inherent in many biological and / or chemical phenomena.

[0079] Susceptible: An individual who is "susceptible to" a disease, disorder, and / or condition is an individual who is at a higher risk than the general population of developing the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition tends to have the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition may not have been diagnosed with the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition may exhibit symptoms of the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition may not exhibit symptoms of the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition develops the disease, disorder, and / or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition does not develop the disease, disorder, and / or condition.

[0080] Therapeutic Agent: As used herein, the term "therapeutic agent" generally refers to any agent that, when administered to a subject, induces a desired effect (e.g., a desired biological, clinical, or pharmacological effect). In some embodiments, an agent is considered a therapeutic agent if it exhibits a statistically significant effect across an appropriate population. In some embodiments, the appropriate population is a population of subjects suffering from and / or susceptible to a disease, disorder, or condition. In some embodiments, the appropriate population is a population of model organisms. In some embodiments, the appropriate population may be defined by one or more criteria, such as age group, sex, genetic background, pre-existing clinical condition, exposure to previous therapy, etc. In some embodiments, a therapeutic agent is a substance that, when administered to a subject in an effective amount, alleviates, ameliorates, relieves, inhibits, prevents, delays the onset of, reduces the severity of, and / or reduces the occurrence of one or more symptoms or characteristics of the disease, disorder, and / or condition of the subject. In some embodiments, a "therapeutic agent" is an agent that has been, or needs to be, approved by a government agency before it can be commercially available for administration to humans. In some embodiments, a "therapeutic agent" is a drug that requires a prescription for administration to a human. In some embodiments, a therapeutic agent is a compound described herein.

[0081] Therapeutically effective amount: As used herein, the term "therapeutically effective amount" refers to an amount of a substance (e.g., a therapeutic agent, composition, and / or formulation) that, when administered as part of a treatment regimen, elicits a desired biological response. In some embodiments, a therapeutically effective amount of a substance is an amount sufficient to treat, diagnose, prevent, and / or delay the onset of a disease, disorder, and / or condition when administered to a subject suffering from or susceptible to the disease, disorder, and / or condition. As will be understood by one of skill in the art, the effective amount of a substance can vary depending on factors such as the desired biological endpoint, the substance being delivered, and the target cell or tissue. For example, an effective amount of a compound in a formulation for treating a disease, disorder, and / or condition is an amount that alleviates, ameliorates, reduces, inhibits, prevents, delays the onset of, reduces the severity of, and / or reduces the occurrence of one or more symptoms or characteristics of the disease, disorder, and / or condition. In some embodiments, a therapeutically effective amount is administered in a single dose. In some embodiments, multiple unit doses are required to deliver a therapeutically effective amount.

[0082] Treatment: As used herein, the terms "treat," "treatment," or "treating" refer to any method used to partially or completely alleviate, ameliorate, reduce, suppress, prevent, delay onset, reduce severity, and / or reduce the occurrence of one or more symptoms or characteristics of a disease, disorder, and / or condition. Treatment may be administered to a subject who does not show signs of the disease, disorder, and / or condition. In some embodiments, treatment may be administered to a subject who shows only early signs of a disease, disorder, and / or condition, for example, for the purpose of reducing the risk of developing pathology associated with the disease, disorder, and / or condition.

[0083] Unit dose: As used herein, the phrase "unit dose" refers to an amount administered as a single dose and / or in a physically discrete unit of pharmaceutical composition. In many embodiments, a unit dose comprises a predetermined amount of an active agent. In some embodiments, a unit dose comprises an entire single dose of a drug. In some embodiments, more than one unit dose is administered to achieve a total single dose. In some embodiments, administration of multiple unit doses is required or expected to be required to achieve the intended effect. A unit dose can be, for example, a liquid volume (e.g., an acceptable carrier) containing a predetermined amount of one or more therapeutic agents, a predetermined amount of one or more therapeutic agents in solid form, a sustained-release formulation or drug delivery device containing a predetermined amount of one or more therapeutic agents, etc. It will be understood that a unit dose can be in a formulation containing any of a variety of ingredients in addition to a therapeutic agent. For example, an acceptable carrier (e.g., a pharmaceutically acceptable carrier), a diluent, a stabilizer, a buffer, a preservative, etc., can be included, as described below. As will be understood by those skilled in the art, in many embodiments, an appropriate total daily dosage of a particular therapeutic agent may comprise a fraction or multiple of a unit dose and may be determined, for example, by an attending physician within the scope of sound medical judgment. In some embodiments, the specific effective dosage level for any particular subject or organism may depend on a variety of factors, including the disorder being treated and the severity of the disorder, the activity of the particular active compound used, the particular composition used, the subject's age, weight, general health, sex, and diet, the time of administration and excretion rate of the particular active compound used, the duration of treatment, drugs and / or additional therapies used in combination with or simultaneously with the particular compound used, and similar factors well known in the medical field.

[0084] Unsaturated: As used herein, the term "unsaturated" means that a moiety has one or more units of unsaturation.

[0085] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure, e.g., R and S configurations, Z and E double bond isomers, and Z and E conformer for each asymmetric center. Thus, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the disclosure. Unless otherwise stated, all tautomeric forms of the compounds are within the scope of the disclosure. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, replacement of hydrogen by deuterium or tritium, or 13 C or 14 Compounds having the structures of the present invention containing carbon substitutions with C-enriched carbons are within the scope of the present disclosure. Such compounds are useful, for example, as analytical tools, probes in biological assays, or as therapeutic agents according to the present disclosure. As will be understood by those skilled in the art, the provided compounds, agents, etc. may be provided as solvates thereof.

[0086] 3. Description of Exemplary Embodiments: In some embodiments, the present disclosure provides: an antibody binding moiety; a target binding moiety; and Optionally, a linker moiety is provided.

[0087] In some embodiments, the antibody binding moiety is uABT. In some embodiments, the target binding moiety can bind to CD38. In some embodiments, the agent is a compound of Formula I, Ia, Ib, II, or III, or a salt thereof. In some embodiments, the present disclosure provides a compound of Formula I, Ia, Ib, II, or III, or a pharmaceutically acceptable salt thereof. Various embodiments of the provided technology are described herein by way of example.

[0088] antibody binding part Among other things, the present disclosure provides agents (e.g., ARMs) comprising an antibody-binding moiety. In some embodiments, the antibody-binding moiety is a universal antibody-binding moiety, capable of binding to antibodies with different Fab regions and different specificities. In some embodiments, the antibody-binding moiety of the present disclosure is a universal antibody-binding moiety that binds to an Fc region. In some embodiments, binding of the universal antibody-binding moiety to the Fc region can occur simultaneously with binding of an Fc receptor (e.g., CD16a) to the same Fc region (e.g., at a different position / amino acid residue in the same Fc region). In some embodiments, upon binding of the universal antibody-binding moiety (e.g., in a provided agent, compound, method, etc.), the Fc region can still interact with the Fc receptor and perform one or more or all of its immune activities, including recruiting immune cells (e.g., effector cells such as NK cells) and / or inducing, generating, promoting, and / or enhancing the activity of the immune system (e.g., antibody-dependent cell-mediated cytotoxicity (ADCC) and / or ADCP) against target cells, tissues, objects, and / or entities.

[0089] A variety of universal antibody binding moieties can be utilized in accordance with the present disclosure. Techniques for identifying and / or evaluating specific antibody binding moieties and universal antibody binding moieties, and / or their use in ARMs, are described in WO / 2019 / 023501 (incorporated herein by reference). Those skilled in the art will appreciate that additional techniques in the art may be suitable for identifying and / or evaluating universal antibody binding moieties suitable for ARMs in accordance with the present disclosure. In some embodiments, the universal antibody binding moieties each independently comprise one or more amino acid residues, natural or non-natural. In some embodiments, the universal antibody binding moieties are: [ka] or a salt form thereof. In some embodiments, the universal antibody binding moiety has the structure: [ka] or a salt form thereof. In some embodiments, the universal antibody binding moiety has a peptide moiety (e.g., R c -(Xaa)z- or a salt form thereof, wherein R c Each of Xaa, z, and Xaa is independently as described herein. In some embodiments, one or more Xaa are independently a non-natural amino acid residue. In some embodiments, the side chains of two or more amino acid residues may be linked together to form a bridge. For example, in some embodiments, the side chains of two cysteine ​​residues may form a disulfide bridge containing -SS- (which may be formed by two -SH groups, as in many proteins). In some embodiments, the universal antibody binding moiety is a cyclic peptide moiety (e.g., [ka] or a salt form thereof). In some embodiments, the universal antibody binding moiety is or comprises R c -(Xaa)z- or [ka] or a salt form thereof, which is or comprises a peptide unit. In some embodiments, -(Xaa)z- is or comprises a peptide unit. In some embodiments, a peptide unit is an amino acid residue (e.g., a "positively charged amino acid residue" at physiological pH about 7.4, Xaa P ), e.g., a residue of an amino acid of formula AI having a positively charged side chain. In some embodiments, the peptide unit comprises R. In some embodiments, at least one Xaa is R. In some embodiments, the peptide unit is or comprises APAR. In some embodiments, the peptide unit is or comprises RAPA. In some embodiments, the peptide unit comprises a side chain that includes an aromatic group ("aromatic amino acid residue", Xaa A) (e.g., residues of amino acids of formula AI). In some embodiments, the peptide unit comprises a positively charged amino acid residue and an aromatic amino acid residue. In some embodiments, the peptide unit comprises W. In some embodiments, the peptide unit comprises a positively charged amino acid residue and an aromatic amino acid residue. In some embodiments, the peptide unit comprises a Xaa A XaaXaa P Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa P XaaXaa A In some embodiments, the peptide unit is or comprises Xaa P Xaa A Xaa P In some embodiments, the peptide unit is or comprises two or more Xaa P Xaa A Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa A Xaa P XaaXaa P Xaa A Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa P Xaa A Xaa A Xaa P In some embodiments, the peptide unit is or comprises Xaa P Xaa P Xaa P Xaa A In some embodiments, the peptide unit is or comprises two or more Xaa A Xaa A Xaa PIn some embodiments, the peptide unit is or comprises: HWRGWA. In some embodiments, the peptide unit is or comprises: WGRR. In some embodiments, the peptide unit is or comprises: RRGW. In some embodiments, the peptide unit is or comprises: NKFRGKYK. In some embodiments, the peptide unit is or comprises: NRFRGKYK. In some embodiments, the peptide unit is or comprises: NARKFYK. In some embodiments, the peptide unit is or comprises: NARKFYKG. In some embodiments, the peptide unit is or comprises: HWRGWV. In some embodiments, the peptide unit is or comprises: KHFRNKD. In some embodiments, the peptide unit is or comprises: positively charged amino acid residues, aromatic amino acid residues, and amino acid residues, e.g., residues of amino acids of formula AI having negatively charged side chains (e.g., "negatively charged amino acid residues" at physiological pH of about 7.4, Xaa N). In some embodiments, the peptide residue is RHRFNKD. In some embodiments, the peptide unit is TY. In some embodiments, the peptide unit is TYK. In some embodiments, the peptide unit is RTY. In some embodiments, the peptide unit is RTYK. In some embodiments, the peptide unit is or includes a sequence selected from PAM. In some embodiments, the peptide unit is WHL. In some embodiments, the peptide unit is ELVW. In some embodiments, the peptide unit is or includes a sequence selected from AWHLGELVW. In some embodiments, the peptide unit is or includes a sequence selected from DCAWHLGELVWCT, wherein the two cysteine ​​residues are capable of forming a disulfide bond as found in naturally occurring proteins. In some embodiments, the peptide unit is or includes a sequence selected from Fc-III. In some embodiments, the peptide unit is or includes a sequence selected from DpLpAWHLGELVW. In some embodiments, the peptide unit is or includes a sequence selected from FcBP-1. In some embodiments, the peptide unit is or comprises a sequence selected from DpLpDCAWHLGELVWCT. In some embodiments, the peptide unit is or comprises a sequence selected from FcBP-2. In some embodiments, the peptide unit is or comprises a sequence selected from CDCAWHLGELVWCTC, where the first and last cysteines and the two central cysteines of the sequence are each independently capable of forming a disulfide bond as in a native protein. In some embodiments, the peptide unit is or comprises a sequence selected from Fc-III-4c. In some embodiments, the peptide unit is or comprises a sequence selected from FcRM. In some embodiments, the peptide unit is or comprises a cyclic peptide unit. In some embodiments, the cyclic peptide unit comprises an amide group formed by the side chain amino group and the C-terminal -COOH.

[0090] In some embodiments, -(Xaa)z- is [X 1 ] p1 [X 2 ] p2 -X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 -[X 13 ] p13 -[X 14 ] p14 [X 15 ] p15 [X 16 ] p16 wherein X is or comprises 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 are independently, for example, an amino acid residue of amino acid formula AI, and each of p1, p2, p13, p14, p15, and p16 is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 Each of X is independently an amino acid residue of an amino acid of formula AI. 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X8 , X 9 , X 10 , X 11 , X 12 , and X 13 Each of X is independently a naturally occurring amino acid residue. 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , and X 13 One or more of are independently a non-natural amino acid residue as described in this disclosure.

[0091] In some embodiments, a peptide unit comprises a functional group on an amino acid residue that can react with a functional group on another amino acid residue. In some embodiments, a peptide unit comprises an amino acid residue having a side chain that comprises a functional group that can react with another functional group on the side chain of another amino acid residue to form a linkage (see, e.g., Table A-1, Table 1, etc.). In some embodiments, a functional group on one amino acid residue is connected to a functional group on another amino acid residue to form a linkage (or bridge). The bond is attached to a backbone atom of the peptide unit and does not include a backbone atom. In some embodiments, a peptide unit comprises a linkage formed by two side chains of non-adjacent amino acid residues. In some embodiments, the linkage is attached to two backbone atoms of two non-adjacent amino acid residues. In some embodiments, both backbone atoms attached to the linkage are carbon atoms. In some embodiments, the linkage is formed by a linkage formed by two side chains of non-adjacent amino acid residues. b It has the structure of L b is the L described in this disclosure a and L a is not a covalent bond. a In some embodiments, L a In some embodiments, -Cy- includes -Cy-, where -Cy- is an optionally substituted heteroaryl. [ka] In some embodiments, L a teeth, [ka] In some embodiments, such L a can be formed by the -N3 group of the side chain of one amino acid residue and the -≡- of the side chain of another amino acid residue. In some embodiments, the linkage is formed through the connection of two thiol groups (e.g., two cysteine ​​residues). In some embodiments, L a In some embodiments, L a is -CH2-SS-CH2-. In some embodiments, the linkage is formed through the connection of an amino group (e.g., -NH2 of the side chain of a lysine residue) and a carboxylic acid group (e.g., -COOH of the side chain of an aspartic acid or glutamic acid residue). In some embodiments, L a In some embodiments, L a In some embodiments, L a is -CHCONH-(CH)-. In some embodiments, L a comprises —C(O)—N(R′)—, where R′ is R, and together with the R groups on the peptide backbone form a ring (e.g., A-34). a is —(CH)—N(R′)—CO—(CH). In some embodiments, —Cy- is optionally substituted phenylene. In some embodiments, —Cy- is optionally substituted 1,2-phenylene. In some embodiments, L a teeth, [ka] In some embodiments, L a teeth, [ka] In some embodiments, La is an optionally substituted divalent C 2-20 In some embodiments, L a is optionally substituted -(CH2)9-CH=CH-(CH2)9-. In some embodiments, L a is -(CH2)3-CH=CH-(CH2)3-.

[0092] In some embodiments, the two amino acid residues joined at the linkage are separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more than 15 amino acid residues between them (excluding the two amino acid residues joined at the linkage). In some embodiments, the number is 1. In some embodiments, the number is 2. In some embodiments, the number is 3. In some embodiments, the number is 4. In some embodiments, the number is 5. In some embodiments, the number is 6. In some embodiments, the number is 7. In some embodiments, the number is 8. In some embodiments, the number is 9. In some embodiments, the number is 10. In some embodiments, the number is 11. In some embodiments, the number is 12. In some embodiments, the number is 13. In some embodiments, the number is 14. In some embodiments, the number is 15.

[0093] In some embodiments, each of p1, p2, p13, p14, p15, and p16 is 0. In some embodiments, -(Xaa)z- is -X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X11 , and X 12 are independently an amino acid residue; X 6 is Xaa A or Xaa P and X 9 is Xaa N and X 12 is Xaa A or Xaa P is. In some embodiments, X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 Each of X is independently an amino acid residue of an amino acid of formula AI described in the present disclosure. 5 is Xaa A or Xaa P In some embodiments, X 5 is Xaa A In some embodiments, X 5 is Xaa P In some embodiments, X 5 is an amino acid residue whose side chain comprises an optionally substituted saturated, partially saturated, or aromatic ring. 5 teeth, [ka] In some embodiments, X 5 teeth, [ka] In some embodiments, X 6 is Xaa A In some embodiments, X 6 is Xaa P In some embodiments, X 6is His. 12 is Xaa A In some embodiments, X 12 is Xaa P In some embodiments, X 9 is Asp. 9 is Glu. 12 teeth, [ka] In some embodiments, X 12 teeth, [ka] In some embodiments, X 7 , X 10 , and X 11 each independently being an amino acid residue having a hydrophobic side chain (a "hydrophobic amino acid residue", Xaa H In some embodiments, X 7 is Xaa H In some embodiments, X 7 teeth, [ka] In some embodiments, X 7 In some embodiments, X is Val. 10 is Xaa H In some embodiments, X 10 is Met. 10 teeth, [ka] In some embodiments, X 11 is Xaa H In some embodiments, X 11 teeth, [ka] In some embodiments, X 8is Gly. 4 is Pro. In some embodiments, X 3 is Lys. 12 -COOH of Lys(X 3 ) and forms an amide bond with the amino group in the side chain of Lys(X 3 The other amino group of ) is connected to a linker moiety and then to a target binding moiety.

[0094] In some embodiments, -(Xaa)z- is -X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; At least two amino acid residues are linked by one or more L b Connected via L b is a C1-C group with 1 to 5 heteroatoms 20 Aliphatic or C1-C 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L bis attached to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 6 is Xaa A or Xaa P and X 9 is Xaa N and X 12 is Xaa A or Xaa P is. In some embodiments, X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, X 5 and X 10 L b In some embodiments, one link L b In some embodiments, X 6 is Xaa A In some embodiments, X 6 is Xaa P In some embodiments, X 6 is His. 9 is Asp. 9 is Glu. 12 is Xaa A In some embodiments, X 12 teeth, [ka] In some embodiments, X 12 teeth, [ka] In some embodiments, X 12 teeth, [ka] In some embodiments, X 4 , X 7 , and X 11 Each of Xaa H In some embodiments, X 4 is Xaa H In some embodiments, X 4 is Ala. 7 is Xaa H In some embodiments, X 7 teeth, [ka] In some embodiments, X 11 is Xaa H In some embodiments, X 11 teeth, [ka] In some embodiments, X 8 is Gly. 3 is Lys. 12 -COOH of Lys(X 3 ) and forms an amide bond with the amino group in the side chain of Lys(X 3 The other amino group of L is connected to a linker moiety and then to a target binding moiety. b teeth, [ka] In some embodiments, L b teeth, [ka] In some embodiments, L bconnects two alpha carbon atoms of two different amino acid residues. 5 and X 10 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH2-SS-CH2-).

[0095] In some embodiments, -(Xaa)z- is -X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 - is or comprises -, wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; At least two amino acid residues are linked by one or more L b Connected via L b is a C1-C group with 1 to 5 heteroatoms 20 Aliphatic or C1-C 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is attached to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 4 is Xaa A and X 5 is Xaa A or Xaa P and X 8 is Xaa N and X 11 is Xaa A is. In some embodiments, X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, one link L b In some embodiments, X 2 and X 12 L b In some embodiments, L b is -CH-SS-CH-. In some embodiments, L b is -CH-CH-S-CH-. In some embodiments, L b teeth, [ka] In some embodiments, L b teeth, [ka] In some embodiments, L bis -CH2CH2CO-N(R')-CH2CH2-. In some embodiments, R' together with the R group on the backbone atom to which -N(R')-CH2CH2- is attached forms a ring, e.g., A-34. In some embodiments, the ring formed is 3, 4, 5, 6, 7, or 8-membered. In some embodiments, the ring formed is monocyclic. In some embodiments, the ring formed is saturated. In some embodiments, L b teeth, [ka] In some embodiments, L b connects two alpha carbon atoms of two different amino acid residues. 4 is Xaa A In some embodiments, X 4 is Tyr. 5 is Xaa A In some embodiments, X 5 is Xaa P In some embodiments, X 5 is His. 8 is Asp. 8 is Glu. X 11 is Tyr. 2 and X 12 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 3 , X 6 , X 9 , and X 10 Each of Xaa H In some embodiments, X 3 is Xaa H In some embodiments, X 3 is Ala. 6 is Xaa H In some embodiments, X 6is Leu. 9 is Xaa H In some embodiments, X 9 is Leu. 9 teeth, [ka] In some embodiments, X 10 is Xaa H In some embodiments, X 10 In some embodiments, X is Val. 10 teeth, [ka] In some embodiments, X 7 In some embodiments, p1 is 1. In some embodiments, X 1 In some embodiments, p13 is 1. In some embodiments, p14, p15, and p16 are 0. In some embodiments, X 13 is a polar uncharged side chain (e.g., a "polar uncharged amino acid residue" at physiological pH, Xaa L In some embodiments, X is an amino acid residue comprising 13 is Thr. In some embodiments, X 13 In some embodiments, p13 is 0. In some embodiments, R c is —NHCHCH(OH)CH. In some embodiments, R c is (R)-NHCHCH(OH)CH. In some embodiments, R c is (S)-NHCH2CH(OH)CH3.

[0096] In some embodiments, -(Xaa)z- is -X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10X 11 X 12 - is or comprises -, wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X 12 are independently an amino acid residue; At least two amino acid residues are linked by one or more L b Connected via L b is a C1-C group with 1 to 5 heteroatoms 20 Aliphatic or C1-C 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is attached to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 5 is Xaa A or Xaa P and X 8 is Xaa N and X 11 is Xaa A In some embodiments, X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, one link L b In some embodiments, there are two or more linked L b In some embodiments, there are two linked L b In some embodiments, X 2 and X 12 L b In some embodiments, X 4 and X 9 L b In some embodiments, X 4 and X 10 L b In some embodiments, L b is -CH-SS-CH-. In some embodiments, L b teeth, [ka] In some embodiments, L b teeth, [ka] In some embodiments, X 2 and X 12 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 4 and X 10 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, X 4 and X 9 L b Connected by L b teeth, [ka] In some embodiments, X 4 and X 9 L b Connected by L b teeth, [ka] In some embodiments, X 5 is Xaa A In some embodiments, X 5 is Xaa P In some embodiments, X 5 is His. 8 is Asp. 8 is Glu. 11 is Tyr. 11 teeth, [ka] In some embodiments, X 2 and X 12 L b Connected by L b is -CH-S-CHCH-. In some embodiments, L b connects two alpha carbon atoms of two different amino acid residues. 3 , X 6 , and X 9 Each of Xaa H In some embodiments, X 3 is Xaa H In some embodiments, X 3 is Ala. 6 is Xaa H In some embodiments, X 6 is Leu. 6 teeth, [ka] In some embodiments, X 9 is Xaa H In some embodiments, X 9 is Leu. 9 teeth, [ka] In some embodiments, X 10 is Xaa H In some embodiments, X 10 In some embodiments, X is Val. 7 In some embodiments, p1 is 1. In some embodiments, X 1 is Xaa N In some embodiments, X 1 is Asp. 1 In some embodiments, p13 is 1. In some embodiments, p14, p15, and p16 are 0. In some embodiments, X 13 is Xaa L In some embodiments, X 13 is Thr. In some embodiments, X 13 is Val.

[0097] In some embodiments, -(Xaa)z- is -X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 X 13 X 14 X 15 X 16 - is or comprises -, wherein X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8, X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , and X 16 are independently an amino acid residue; At least two amino acid residues are linked together by the L b Connected via L b is a C1-C group with 1 to 5 heteroatoms 20 Aliphatic or C1-C 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy—, —O—, —S—, —SS—, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)2N(R′)—, —C(O)S—, or —C(O)O—; L b is attached to a backbone atom of one amino acid residue and a backbone atom of another amino acid residue, but does not include the backbone atom, X 3 is Xaa N and X 6 is Xaa A and X 7 is Xaa A or Xaa P and X 9 is Xaa N and X 13 is Xaa A is. In some embodiments, X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , and X12 are independently an amino acid residue of an amino acid of formula AI described in the present disclosure. In some embodiments, two non-adjacent amino acid residues are b In some embodiments, one link L b In some embodiments, there are two or more linked L b In some embodiments, there are two linked L b In some embodiments, X 2 L b By X 16 In some embodiments, X 4 L b By X 14 In some embodiments, X 2 and X 16 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b In some embodiments, X is -CH-SS-CH-. 4 and X 14 Both of the amino acids are Cys, and the two -SH groups in their side chains form -SS- (L b is -CH-SS-CH-). In some embodiments, L b connects two alpha carbon atoms of two different amino acid residues. 3 is Asp. 3 is Glu. 5 is Xaa H In some embodiments, X 5 is Ala. 6 is Xaa A In some embodiments, X 6 is Tyr. 7 is Xaa A In some embodiments, X 7 is Xaa P In some embodiments, X 7 is His. 8 is XaaH In some embodiments, X 8 is Ala. 9 is Gly. 10 is Asp. 10 is Glu. 11 is Xaa H In some embodiments, X 11 is Leu. 12 is Xaa H In some embodiments, X 12 In some embodiments, X is Val. 13 is Xaa A In some embodiments, X 13 is Tyr. 15 is Xaa L In some embodiments, X 15 is Thr. In some embodiments, X 15 In some embodiments, p1 is 1. In some embodiments, X 1 is Xaa N In some embodiments, X 1 is Asp. 1 is Glu.

[0098] As will be appreciated by those skilled in the art, an amino acid residue may be substituted by another amino acid residue having similar properties, e.g., a Xaa H (e.g., Val, Leu, etc.) can be replaced by another Xaa H (e.g., Leu, Ile, Ala, etc.), and certain Xaa A is another Xaa A Xaa may be substituted with P is another Xaa P Xaa may be substituted with N is another Xaa N Xaa may be substituted with L is another Xaa Lmay be substituted with, etc.

[0099] In some embodiments, the antibody binding moiety, e.g., universal antibody binding moiety, is or comprises an optionally substituted moiety of Table A-1. In some embodiments, the antibody binding moiety, e.g., universal antibody binding moiety, is selected from Table A-1.

[0100] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8]

[0101] In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-1. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-2. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-3. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-4. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-5. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-6. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-7. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-8. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-9. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-10. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-11. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-12. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-13. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-14. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-15. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-16. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-17. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-18. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-19.In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-20. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-21. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-22. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-23. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-24. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-25. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-26. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-27. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-28. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-29. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-30. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-31. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-32. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-33. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-34. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-35. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-36. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-37.In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-38. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-39. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-40. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-41. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-42. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-43. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-44. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-45. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-46. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-47. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-48. In some embodiments, the universal antibody binding moiety is or comprises an optionally substituted A-49.

[0102] In some embodiments, the universal antibody binding moiety is A-1. In some embodiments, the universal antibody binding moiety is A-2. In some embodiments, the universal antibody binding moiety is A-3. In some embodiments, the universal antibody binding moiety is A-4. In some embodiments, the universal antibody binding moiety is A-5. In some embodiments, the universal antibody binding moiety is A-6. In some embodiments, the universal antibody binding moiety is A-7. In some embodiments, the universal antibody binding moiety is A-8. In some embodiments, the universal antibody binding moiety is A-9. In some embodiments, the universal antibody binding moiety is A-10. In some embodiments, the universal antibody binding moiety is A-11. In some embodiments, the universal antibody binding moiety is A-12. In some embodiments, the universal antibody binding moiety is A-13. In some embodiments, the universal antibody binding moiety is A-14. In some embodiments, the universal antibody binding moiety is A-15. In some embodiments, the universal antibody binding moiety is A-16. In some embodiments, the universal antibody binding moiety is A-17. In some embodiments, the universal antibody binding moiety is A-18. In some embodiments, the universal antibody binding moiety is A-19. In some embodiments, the universal antibody binding moiety is A-20. In some embodiments, the universal antibody binding moiety is A-21. In some embodiments, the universal antibody binding moiety is A-22. In some embodiments, the universal antibody binding moiety is A-23. In some embodiments, the universal antibody binding moiety is A-24. In some embodiments, the universal antibody binding moiety is A-25. In some embodiments, the universal antibody binding moiety is A-26. In some embodiments, the universal antibody binding moiety is A-27. In some embodiments, the universal antibody binding moiety is A-28. In some embodiments, the universal antibody binding moiety is A-29. In some embodiments, the universal antibody binding moiety is A-30. In some embodiments, the universal antibody binding moiety is A-31.In some embodiments, the universal antibody binding moiety is A-32. In some embodiments, the universal antibody binding moiety is A-33. In some embodiments, the universal antibody binding moiety is A-34. In some embodiments, the universal antibody binding moiety is A-35. In some embodiments, the universal antibody binding moiety is A-36. In some embodiments, the universal antibody binding moiety is A-37. In some embodiments, the universal antibody binding moiety is A-38. In some embodiments, the universal antibody binding moiety is A-39. In some embodiments, the universal antibody binding moiety is A-40. In some embodiments, the universal antibody binding moiety is A-41. In some embodiments, the universal antibody binding moiety is A-42. In some embodiments, the universal antibody binding moiety is A-43. In some embodiments, the universal antibody binding moiety is A-44. In some embodiments, the universal antibody binding moiety is A-45. In some embodiments, the universal antibody binding moiety is A-46. In some embodiments, the universal antibody binding moiety is A-47. In some embodiments, the universal antibody binding moiety is A-48. In some embodiments, the universal antibody binding moiety is A-49.

[0103] In some embodiments, the antibody binding moiety is [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] In some embodiments, the antibody binding moiety is or comprises: [ka] is or contains

[0104] In some embodiments, the universal antibody binding moiety comprises a peptide unit and is connected to a linker moiety via the C-terminus of the peptide unit. In some embodiments, it is connected to a linker moiety via the N-terminus of the peptide unit. In some embodiments, it is connected to a linker via a side chain group of the peptide unit. In some embodiments, the universal antibody binding moiety comprises a peptide unit and, optionally, is connected to a target binding moiety via a linker moiety via the C-terminus of the peptide unit. In some embodiments, the universal antibody binding moiety comprises a peptide unit and, optionally, is connected to a target binding moiety via a linker moiety via the N-terminus of the peptide unit. In some embodiments, the universal antibody binding moiety comprises a peptide unit and, optionally, is connected to a target binding moiety via a linker moiety via a side chain of the peptide unit.

[0105] In some embodiments, the antibody binding moiety, e.g., universal antibody binding moiety, is or comprises a small molecular entity, e.g., having a molecular weight of less than 10,000, 9,000, 8,000, 7,000, 6,000, 5,000, 4,000, 3,000, 2,000, 1,500, 1,000, etc. Suitable such antibody binding moieties include, e.g., small molecule Fc binder moieties such as those described in US 9,745,339, US 201 / 30131321. In some embodiments, the antibody binding moiety is of a structure such that the corresponding compound is a compound described in US 9,745,339 or US 2013 / 0131321 (each of which compounds is independently incorporated herein by reference). In some embodiments, the ABT is of a structure such that the H-ABT is a compound described in US9,745,339 or US2013 / 0131321 (each of which compounds is independently incorporated herein by reference). In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0106] In some embodiments, the antibody binding moiety, e.g., ABT, is optionally substituted [ka] In some embodiments, the ABT is or comprises: [ka] In some embodiments, ABT is or comprises optionally substituted [ka] In some embodiments, the ABT is or comprises: [ka] In some embodiments, ABT is or comprises optionally substituted [ka] In some embodiments, the ABT is or comprises: [ka] In some embodiments, ABT is or comprises optionally substituted [ka] In some embodiments, the ABT is or comprises: [ka] is or contains

[0107] In some embodiments, the antibody binding moiety is a triazine moiety, e.g., as described in US2009 / 0286693. In some embodiments, the antibody binding moiety is of a structure such that its corresponding compound is a compound described in US2009 / 0286693 (these compounds are independently incorporated by reference herein). In some embodiments, the ABT is of a structure such that H-ABT is a compound described in US2009 / 0286693 (these compounds are independently incorporated by reference herein). In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0108] In some embodiments, the antibody-binding moiety is a triazine moiety, such as those described in Teng, et al., A strategy for the generation of biomimetic ligands for affinity chromatography. Combinatorial synthesis and biological evaluation of an IgG binding ligand, J. Mol. Recognit. 1999;12:67-75 ("Teng"). In some embodiments, the antibody-binding moiety is structured such that its corresponding compound is a compound described in Teng (these compounds are independently incorporated by reference herein). In some embodiments, the ABT is structured such that H-ABT is a compound described in Teng (these compounds are independently incorporated by reference herein). In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0109] In some embodiments, the antibody binding moiety is a triazine moiety, such as those described in Uttamchandani, et al., Microarrays of Tagged Combinatorial Triazine Libraries in the Discovery of Small-Molecule Ligands of Human IgG, J Comb Chem. 2004 Nov-Dec;6(6):862-8 ("Uttamchandani"). In some embodiments, the antibody binding moiety is of a structure such that its corresponding compound is a compound described in Uttamchandani (these compounds are independently incorporated by reference herein). In some embodiments, the ABT is of a structure such that H-ABT is a compound described in Uttamchandani (these compounds are independently incorporated by reference herein). In some embodiments, such compounds are capable of binding to an antibody. In some embodiments, such compounds are capable of binding to the Fc region of an antibody.

[0110] In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein A. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein G. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein L. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein Z. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein LG. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein LA. In some embodiments, the antibody binding moiety binds to one or more binding sites of Protein AG. In some embodiments, the antibody binding moiety is described in Choe, W., Durgannavar, TA, & Chung, SJ (2016). Fc-binding ligands of immunoglobulin G: An overview of high affinity proteins and peptides. Materials, 9(12). https: / / doi.org / 10.3390 / ma9120994.

[0111] In some embodiments, the antibody binding moiety is capable of binding to a nucleotide binding site. In some embodiments, the antibody binding moiety is a small molecule moiety capable of binding to a nucleotide binding site. In some embodiments, the small molecule is tryptamine. In some embodiments, the ABT is structured such that H-ABT is tryptamine. A particularly useful technique was described in Mustafaoglu, et al., Antibody Purification via Affinity Membrane Chromatography Method Utilizing Nucleotide Binding Site Targeting With A Small Molecule, Analyst. 2016 November 28;141(24):6571-6582.

[0112] Many techniques are available for identifying and / or evaluating and / or characterizing antibody binding moieties, including universal antibody binding moieties, and their use in ARMs (e.g., those described in WO / 2019 / 023501) (these techniques are incorporated herein by reference). In some embodiments, the antibody binding moiety is a moiety (e.g., a small molecule moiety, a peptide moiety, a nucleic acid moiety, etc.) that can selectively bind to IgG and, when used in an ARM, can provide and / or stimulate ADCC and / or ADCP. In some embodiments, peptide display techniques (e.g., phase display, acellular display, etc.) can be used to identify the antibody binding moiety. In some embodiments, the antibody binding moiety is a moiety (e.g., a small molecule moiety, a peptide moiety, a nucleic acid moiety, etc.) that can bind to IgG and, optionally, compete with known antibody binders (e.g., Protein A, Protein G, Protein L, etc.).

[0113] As will be appreciated by those skilled in the art, antibodies of various properties and activities (e.g., antibodies that recognize different antigens, antibodies with optional modifications, etc.) can be recruited by the antibody binding moieties described herein. In some embodiments, such antibodies include antibodies administered to a subject, for example, for therapeutic purposes. In some embodiments, antibodies recruited by antibody binding moieties include antibodies against different antigens. In some embodiments, antibodies recruited by antibody binding moieties include antibodies whose antigen is not present on the surface or cell membrane of a target cell (e.g., a target cell such as a cancer cell). In some embodiments, antibodies recruited by antibody binding moieties include antibodies whose antigen is not present on the surface or cell membrane of a target (e.g., a target cell such as a cancer cell). In some embodiments, an antigen on the surface of a target cell may interfere with the structure, conformation, and / or one or more properties and / or activities of a recruited antibody that binds to such antigen. In some embodiments, as will be appreciated by those skilled in the art, the provided technology comprises universal antibody binding moieties that recruit antibodies with diverse specificities, and wherein no more than 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% percent of the recruited antibodies are directed against the same antigen, protein, lipid, carbohydrate, etc. Among other advantages of the present disclosure, the provided technology comprises universal antibody binding moieties, allowing for utilization of a diverse pool of antibodies, such as those present in serum. In some embodiments, a universal antibody binding moiety of the present disclosure (e.g., in an ARM) is contacted with multiple antibodies, wherein no more than 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% percent of the antibodies are directed against the same antigen, protein, lipid, carbohydrate, etc.

[0114] CD38 CD38 (cluster of differentiation 38, also known as cyclic ADP-ribose hydrolase) is expressed by various cell types and performs several functions. As a glycoprotein, CD38 is expressed on many immune cells (e.g., CD4 + , CD8 + It has been reported to be found on the surface of various types of cells, including B lymphocytes, B lymphocytes, and natural killer cells. Other functions of CD38, such as cell adhesion, signal transduction, and calcium signaling, have also been reported. In various embodiments, the CD38 is human CD38.

[0115] In some embodiments, CD38 has been reported to be a lineage-independent type II transmembrane glycoprotein that synthesizes and hydrolyzes cyclic adenosine 5'-diphosphate ribose, an intracellular calcium ion-mobilizing messenger. According to reports, the release of soluble proteins and the ability of membrane-bound proteins to be internalized may indicate both extracellular and intracellular functions of the protein. In various cases, CD38 has been reported to have an N-terminal cytoplasmic tail, a single transmembrane domain, and a C-terminal extracellular region with four N-glycosylation sites. Crystal structure analysis has shown that the functional molecule is a dimer, with the central portion containing the catalytic site. It has been reported that CD38 can be used as a prognostic marker for patients with chronic lymphocytic leukemia. Alternative splicing has been reported, which can result in multiple transcript variants.

[0116] CD38 has been reported to be expressed on immune system cells, such as T cells or B cells, in healthy individuals. In some embodiments, certain conditions, disorders, or diseases are observed to have increased levels of CD38 expression and / or activity in cells, and typically do not have CD38 or have lower levels of CD38.

[0117] CD38 is associated with various conditions, disorders or diseases, such as HIV infection and various cancers (e.g., leukemia, myeloma, solid tumors, chronic lymphocytic leukemia (CLL), multiple myeloma (MM), acute promyelocytic leukemia (APL), non-Hodgkin's lymphoma, B-cell and T-cell acute lymphoblastic leukemia, acute myeloid leukemia, Hodgkin's lymphoma, chronic myeloid leukemia, etc.).

[0118] Daratumumab, an antibody that targets CD38, is approved for the treatment of multiple myeloma.

[0119] target binding moiety Various types and chemical classes of target-binding moieties can be utilized in accordance with the present disclosure. In particular, compounds of the present disclosure include target-binding moieties capable of binding to CD38. In some embodiments, the target-binding moiety binds to a specific agent, such as CD38. In some embodiments, the target-binding moiety is or includes a peptide moiety. In some embodiments, the target-binding moiety is or includes a nucleic acid agent, such as an aptamer. In some embodiments, the target-binding moiety is or includes a lipid moiety. Specific types of target-binding moieties are described below. Those skilled in the art will understand that other types of target-binding moieties, including many known in the art, can also be utilized in accordance with the present disclosure. As will be appreciated by those skilled in the art, various techniques are readily available and can be utilized to assess and confirm CD38 binding. Particular useful techniques are described in the Examples.

[0120] a. Small molecules In some embodiments, the target binding moiety is a small molecule moiety. In some embodiments, the small molecule moiety has a molecular weight of 8000, 7000, 6000, 5000, 4000, 3000, 2000, 1500, 1000, 900, 800, 700, or 600 or less. In some embodiments, the small molecule moiety has a molecular weight of 8000 or less. In some embodiments, the small molecule moiety has a molecular weight of 7000 or less. In some embodiments, the small molecule moiety has a molecular weight of 6000 or less. In some embodiments, the small molecule moiety has a molecular weight of 5000 or less. In some embodiments, the small molecule moiety has a molecular weight of 4000 or less. In some embodiments, the small molecule moiety has a molecular weight of 3000 or less. In some embodiments, the small molecule moiety has a molecular weight of 2000 or less. In some embodiments, the small molecule moiety has a molecular weight of 1500 or less. In some embodiments, the small molecule moiety has a molecular weight of 1000 or less. In some embodiments, the small molecule moiety has a molecular weight of 900 or less. Among other things, the present disclosure encompasses the recognition that small molecule target binding moieties can be capable of binding to markers (eg, CD38) on the outside, on the surface, and / or inside of a target (eg, a cancer cell).

[0121] In some embodiments, the small molecule target binding moiety is or comprises a moiety that selectively binds to a protein or fragment thereof (eg, CD38).

[0122] b. Peptide drugs In some embodiments, the target-binding moiety is or comprises a peptide agent. In some embodiments, the target-binding moiety is a peptide moiety. In some embodiments, the peptide moiety may be linear or cyclic. In some embodiments, the target-binding moiety is or comprises a cyclic peptide moiety. A variety of peptide target-binding moieties are known in the art and can be utilized in accordance with the present disclosure.

[0123] In some embodiments, the target binding moiety is or comprises a peptide aptamer agent.

[0124] c. aptamer agent In some embodiments, the target binding moiety is or comprises a nucleic acid agent. In some embodiments, the target binding moiety is or comprises an oligonucleotide moiety. In some embodiments, the target binding moiety is or comprises an aptamer agent. A variety of aptamer agents are known in the art or can be easily developed using common techniques and can be utilized in the techniques provided in accordance with the present disclosure.

[0125] In some embodiments, the target-binding moiety (e.g., capable of binding to CD38) is or comprises a peptide moiety. In some embodiments, the peptide moiety is or comprises (Xaa)y or a salt form thereof as described herein. In some embodiments, the target-binding moiety (e.g., capable of binding to CD38) is a peptide moiety, e.g., [ka] or a salt thereof, wherein each Xaa is independently a residue of an amino acid or amino acid analog; y is between 5 and 20; L T are each independently a linker moiety connecting two residues from an amino acid or amino acid analog, and are independently a covalent bond or an optionally substituted divalent group selected from C-C aliphatic or C-C heteroaliphatic having 1 to 5 heteroatoms, wherein one or more methylene units of the group are optionally and independently replaced by -C(R')-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)-, -S(O)N(R')-, -C(O)S-, or -C(O)O-; Each R c independently, -L a -R', t is 0 to 50; Each L a are independently a covalent bond or C-C 20 Aliphatic or C1-C with 1-5 heteroatoms 20 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced by —C(R′)2—, —Cy-, —O—, —S—, —SS-, —N(R′)—, —C(O)—, —C(S)—, —C(NR′)—, —C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —S(O)—, —S(O)N(R′)—, —C(O)S—, or —C(O)O—; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C 3-20 Alicyclic ring, C 6-20 an aryl ring, a 5- to 20-membered heteroaryl ring having 1 to 10 heteroatoms, and a 3- to 20-membered heterocyclyl ring having 1 to 10 heteroatoms; each R' is independently -R, -C(O)R, -COR, or -SOR; Each R is independently -H or C 1-30 Aliphatic, C with 1-10 heteroatoms 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C with 1-10 heteroatoms 6-30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms, and 3-30 membered heterocyclyl having 1-10 heteroatoms; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms.

[0126] In some embodiments, [ka] is.

[0127] In some embodiments, each Xaa is independently an amino acid residue. In some embodiments, Xaa is an amino acid analog residue. In some embodiments, one or more Xaa are independently natural amino acid residues. In some embodiments, one or more Xaa are independently unnatural amino acid residues. In some embodiments, the side chains of two or more amino acid residues may be linked together to form a bridge. In some embodiments, R c and the side chains of the amino acid residues may be linked together to form a bridge. In some embodiments, each bridge is independently a , L b , or L T In some embodiments, each bridge independently has the structure: a In some embodiments, each bridge independently has the structure: b In some embodiments, each bridge independently has the structure: T For example, in some embodiments, the side chains of two cysteine ​​residues may form a disulfide bridge containing -SS- (which may be formed by two -SH groups, as in many proteins). In some embodiments, R c -L a -R, and Xaa is a residue of an amino acid having the structure of formula AI, where R a2 and R a3 One of the is R, and R c The R in a2 and R a3 forms a covalent bond with one of the

[0128] In some embodiments, -(Xaa)y- is -Xaa T1 -Xaa T2 -(Xaa)y'-Xaa T3 -Xaa T4 -Xaa T5 - is or contains During the ceremony, y' is 0 to 8, Xaa T1 is a residue of an amino acid or amino acid analogue in which the side chain is substituted with a C1-C8 aliphatic group, Xaa T2 is a residue of an amino acid or amino acid analogue whose side chain contains an optionally substituted aromatic group or is an optionally substituted C3-C8 aliphatic; Xaa T3 is a residue of an amino acid or amino acid analog whose side chain is an optionally substituted C2-C8 aliphatic; Xaa T4 is a residue of an amino acid or amino acid analogue whose side chain contains an optionally substituted aromatic group or is an optionally substituted C3-C8 aliphatic; Xaa T5 is a residue of an amino acid or amino acid analog in which the side chain is substituted with a C1-C8 aliphatic group.

[0129] In some embodiments, y' is 0. In some embodiments, y' is 1. In some embodiments, y' is 2. In some embodiments, y' is 3. In some embodiments, y' is 4. In some embodiments, y' is 5. In some embodiments, y' is 6. In some embodiments, y' is 7. In some embodiments, y' is 8.

[0130] In some embodiments, Xaa T1 In some embodiments, Xaa includes a substituted C1-C8 aliphatic. T1 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T1The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T1 The side chain of Xaa is C2-C8 alkyl. T1 The side chain of Xaa is or comprises an optionally substituted straight chain C2-C8 alkyl. T1 The side chain of Xaa is a straight chain C2-C8 alkyl. In some embodiments, the side chain is n-pentyl. In some embodiments, Xaa T1 is (S)-NH-CH(n-CH 11 )—C(O)—. In some embodiments, Xaa T1 The side chain of is or comprises an aromatic group. In some embodiments, the side chain is -CH2-R, where -CH2- is optionally substituted and R is an optionally substituted aryl or heteroaryl. In some embodiments, the side chain is a side chain of Y, W, S, K, or K(MePEG4c). In some embodiments, the side chain is a side chain of Y, W, or S. In some embodiments, Xaa T1 is a residue of Y. In some embodiments, Xaa T1 is a residue of W. In some embodiments, Xaa T1 is a residue of S. In some embodiments, Xaa T1 is a residue of K. In some embodiments, Xaa T1 is the residue of K(MePEG4c).

[0131] In some embodiments, Xaa T2 is or includes an aromatic group. T2is -CH2-R, where -CH2- is optionally substituted and R is as described herein. In some embodiments, R is an optionally substituted aryl or heteroaryl. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is 4-hydroxyphenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, the side chain is of Y or W. In some embodiments, Xaa T2 is a residue of Y. In some embodiments, Xaa T2 is a residue of W. In some embodiments, Xaa T2 is a residue of Bph. T2 In some embodiments, Xaa includes a substituted C1-C8 aliphatic. T2 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T2 The side chain of Xaa is or comprises an optionally substituted C3-C8 aliphatic. T2 The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T2 The side chain of Xaa is C2-C8 alkyl. T2 The side chain of Xaa is or comprises an optionally substituted straight chain C2-C8 alkyl. T2 The side chain of Xaa is a straight chain C2-C8 alkyl. T2 The side chain of Xaa is a branched C3-C8 alkyl. In some embodiments, the side chain is n-pentyl. In some embodiments, Xaa T2 is (S)-NH-CH(n-CH 11 )-C(O)-. In some embodiments, the side chain is (CH3)2CHCH2-. In some embodiments, Xaa T2 is a residue of L. In some embodiments, Xaa T2 is the residue of A.

[0132] In some embodiments, Xaa T3 In some embodiments, Xaa includes a substituted C1-C8 aliphatic. T3 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T3 The side chain of Xaa is or comprises an optionally substituted C3-C8 aliphatic. T3 The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T3 The side chain of Xaa is C2-C8 alkyl. T3 The side chain of Xaa is or comprises an optionally substituted straight chain C2-C8 alkyl. T3 The side chain of Xaa is a straight chain C2-C8 alkyl. T3 The side chain of Xaa is a branched C3-C8 alkyl. In some embodiments, the side chain is n-pentyl. In some embodiments, Xaa T3 is a residue of Ahp. In some embodiments, the side chain is L, V, or T. In some embodiments, Xaa T3 is a residue of L. In some embodiments, Xaa T3 is a residue of V. In some embodiments, Xaa T3 is a residue of T. In some embodiments, Xaa T3 is two or more sp 3 In some embodiments, Xaa T3 comprises a side chain comprising two or more groups that are each independently -CH2- or -CH3. T3 contains a polar side chain, including, for example, —OH, —SO—, etc. In some embodiments, Xaa T3 is a residue of Hse (homoserine). T3 is the residue of MetO2 (methionine sulfone).

[0133] In some embodiments, Xaa T4is or includes an aromatic group. T4 is -CH2-R, where -CH2- is optionally substituted and R is as described herein. In some embodiments, R is an optionally substituted aryl or heteroaryl. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is 4-hydroxyphenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, the side chain is of Y or W. In some embodiments, Xaa T4 is a residue of Y. In some embodiments, Xaa T4 is a residue of W. In some embodiments, Xaa T4 is a residue of Bph. T4 In some embodiments, Xaa includes a substituted C1-C8 aliphatic. T4 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T4 The side chain of Xaa is or comprises an optionally substituted C3-C8 aliphatic. T4 The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T4 The side chain of Xaa is C2-C8 alkyl. T4 The side chain of Xaa is or comprises an optionally substituted straight chain C2-C8 alkyl. T4 The side chain of Xaa is a straight chain C2-C8 alkyl. T4 The side chain of Xaa is a branched C3-C8 alkyl. In some embodiments, the side chain is n-pentyl. In some embodiments, the side chain is isopropyl. In some embodiments, Xaa T4 is a residue of V. In some embodiments, Xaa T4 is the residue of Ahp.

[0134] In some embodiments, Xaa T5is the substituted C1-C 20 In some embodiments, Xaa T5 is the substituted C1-C 15 In some embodiments, Xaa T5 is the substituted C1-C 10 In some embodiments, Xaa T5 In some embodiments, Xaa includes a substituted C1-C8 aliphatic. T5 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T5 The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T5 The side chain of Xaa is C2-C8 alkyl. T5 The side chain of Xaa is or comprises an optionally substituted straight chain C2-C8 alkyl. T5 The side chain of Xaa is a straight chain C2-C8 alkyl. In some embodiments, the side chain is n-pentyl. In some embodiments, Xaa T5 is (S)-NH-CH(n-CH 11 )—C(O)—. In some embodiments, Xaa T5 The side chain of is or comprises an aromatic group. In some embodiments, the side chain is -CH2-R, where -CH2- is optionally substituted and R is an optionally substituted aryl or heteroaryl. In some embodiments, R is an optionally substituted phenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, the side chain is the side chain of Y, W, or S. In some embodiments, Xaa T5 is a residue of Y. In some embodiments, Xaa T5 is a residue of W. In some embodiments, Xaa T5 is a residue of Bph. T5 is a residue of S. In some embodiments, Xaa T5 is a residue of Ado. T5is a residue of Ano. T5 is a residue of PhNle. T5 is the residue of PhNva.

[0135] In some embodiments, Xaa T1 The side chain of Xaa is or includes the side chain of Ahp or Y. T2 The side chain of Xaa is or includes the side chain of Y, W, Ahp, or Bph. T3 The side chain of Xaa is or includes the side chain of L, C, or Ahp. T4 The side chain of Xaa is or includes the side chain of Bph or V. T5 The side chain of is or comprises the side chain of Ahp or Bph.

[0136] In some embodiments, Xaa T1 is a residue of Ahp or Y. In some embodiments, Xaa T2 is a residue of Y, W, Ahp, or Bph. T3 is a residue of L, C, or Ahp. T4 is a residue of Bph or V. In some embodiments, Xaa T5 is a residue of Ahp or Bph.

[0137] In some embodiments, -(Xaa)y- is -(Xaa) a1 -(Xaa) a2 -(Xaa) a3 -(Xaa) a4 -(Xaa) a5 -(Xaa) a6 -(Xaa) a7 -(Xaa) a8 -(Xaa) a9 -(Xaa) a10 -(Xaa) a11 -(Xaa) a12 -(Xaa) a13 - is or contains During the ceremony, each of a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and a13 independently represents an integer of 0 to 5; (Xaa) a3 is Xaa T1 is or contains (Xaa) a4 is Xaa T2 is or contains (Xaa) a9 is Xaa T3 is or contains (Xaa) a10 is Xaa T4 is or contains (Xaa) a11 is Xaa T5 is or contains

[0138] In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and / or a13 are independently 0. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and / or a13 are independently 1. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and / or a13 are independently 2. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and / or a13 are independently 3. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and / or a13 are independently 4. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and / or a13 are independently 5. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and a13 are 1.

[0139] In some embodiments, (Xaa) a1is or includes A. In some embodiments, a1 is 1 and (Xaa) a1 is a residue of A. Other residues can also be utilized. For example, in some embodiments, (Xaa) a1 is or comprises K. In some embodiments, K is connected to another moiety, e.g., an antibody binding moiety, optionally via a linker. In some embodiments, (Xaa) a1 is or includes K(MePEG4c) (CH3O(CH2CHO)3CH2CH2C(O) attached to the amino group of the side chain of K; see exemplary structures described herein). In some embodiments, a1 is 0. In some embodiments, (Xaa) a1 The Xaa (e.g., the N-terminal residue) of (Xaa) can be replaced by another Xaa described herein (e.g., (Xaa) a13 Xaa of the N-terminal residue, Xaa of the C-terminal residue, etc. For example, in some embodiments, a linker links the N-terminal residue through its amino group to the C-terminal cysteine ​​through its -S- (e.g., in the case of -C(O)-CH-, -C(O)- is bonded to the amino group and -CH- is bonded to -S-).

[0140] In some embodiments, (Xaa) a2 is or comprises a residue whose side chain contains a heteroatom, OH, or NH. In some embodiments, (Xaa) a2 is or contains a residue containing a polar or charged side chain. Other types of residues, such as residues containing hydrophobic aliphatic side chains (e.g., A), can also be utilized. In some embodiments, (Xaa) a2 are compounds with side chains R, S, D, Y, A, W, K, 4Py2NH2 ((S)-2-amino-3-(2-aminopyridin-4-yl)propanoic acid), Cit (citrulline), F3G (3-guanidinophenylalanine), hCit (2-amino-5-(carbamoylamino)hexanoic acid; CAS: 201485-17-8), K (MePEG4c), RNdMe (N 5-[(dimethylamino)iminomethyl]-L-ornithine; CAS: 1185841-84-2), RNMe(N 5 -[Imino(methylamino)methyl]-acetate-L-ornithine, CAS: 1135616-49-7), or RNNdMe(N 5 In some embodiments, (Xaa) is or comprises a residue that is the side chain of -[(methylamino)(methylimino)methyl]-L-ornithine. a2 is or includes a residue whose side chain is the side chain of R, S, D, Y, A, or W. In some embodiments, (Xaa) a2 is or includes a residue of R, S, D, Y, A, W, K, 4Py2NH2, Cit, F3G, hCit, K(MePEG4c), RNdMe, RNMe, or RNNdMe. a2 is or includes a residue of R, S, D, Y, A, or W. In some embodiments, (Xaa) a2 is or includes R. In some embodiments, (Xaa) a2 is or includes S. In some embodiments, (Xaa) a2 is or includes D. In some embodiments, (Xaa) a2 is or includes Y. In some embodiments, (Xaa) a2 is or includes W. In some embodiments, (Xaa) a2 is or includes A. In some embodiments, (Xaa) a2 is or includes S. In some embodiments, (Xaa) a2 is or includes K. In some embodiments, (Xaa) a2 In some embodiments, (Xaa) is or comprises 4PyNH. a2 In some embodiments, (Xaa) is or includes Cit. a2 In some embodiments, (Xaa) is or comprises F3G. a2In some embodiments, (Xaa) is or includes hCit. a2 is or comprises K(MePEG4c). In some embodiments, (Xaa) a2 In some embodiments, (Xaa) is or comprises RNdMe. a2 In some embodiments, (Xaa) is or comprises RNMe. a2 In some embodiments, a2 is 1.

[0141] In some embodiments, a3 is 1. In some embodiments, (Xaa) a3 is Xaa as described herein T1 is.

[0142] In some embodiments, a4 is 1. In some embodiments, (Xaa) a4 is Xaa as described herein T2 is.

[0143] In some embodiments, (Xaa) a5 is Xaa T1 In some embodiments, (Xaa) a5 is or comprises a residue whose side chain comprises an aromatic group. a5 is or comprises a residue whose side chain contains a heteroatom, OH, or NH. In some embodiments, (Xaa) a5 is or contains a residue containing a polar or charged side chain. Other types of residues, such as residues containing hydrophobic aliphatic side chains (e.g., A), can also be utilized. In some embodiments, (Xaa) a5 is or includes a residue whose side chain is the side chain of H, A, Y, S, L, W, or WN. In some embodiments, (Xaa) a5 is or includes a residue whose side chain is the side chain of H, A, Y, S, L, or W. In some embodiments, (Xaa) a5is or includes a residue of H, A, Y, S, L, W, or WN. In some embodiments, (Xaa) a5 is or includes a residue of H, A, Y, S, L, or W. In some embodiments, (Xaa) a5 is or includes H. In some embodiments, (Xaa) a5 is or includes A. In some embodiments, (Xaa) a5 is or includes Y. In some embodiments, (Xaa) a5 is or includes S. In some embodiments, (Xaa) a5 is or includes L. In some embodiments, (Xaa) a5 is or includes W. In some embodiments, (Xaa) a5 is or includes W6N. In some embodiments, a5 is 1.

[0144] In some embodiments, (Xaa) a6 is or contains a residue containing a polar or charged side chain. Other types of residues, such as residues containing hydrophobic aliphatic side chains (e.g., A), can also be utilized. In some embodiments, (Xaa) a6 is or includes a residue that does not contain a side chain. In some embodiments, (Xaa) a6 is or includes a residue whose side chain is the side chain of D, R, A, or Y. In some embodiments, (Xaa) a6 is or includes a residue of D, A, G, R, or Y. In some embodiments, (Xaa) a6 is or includes D. In some embodiments, (Xaa) a6 is or includes A. In some embodiments, (Xaa) a6 is or includes G. In some embodiments, (Xaa) a6 is or includes R. In some embodiments, (Xaa) a6 is or includes Y. In some embodiments, a6 is 1.

[0145] In some embodiments, (Xaa) a7 is or comprises a residue containing a polar or charged side chain. Other types of residues, such as residues containing hydrophobic aliphatic side chains (e.g., A), can also be utilized. In some embodiments, polar or charged amino acid residues may provide particular benefits (e.g., improved solubility for manufacturing, administration, delivery, activity, etc.). In some embodiments, (Xaa) a7 is or includes a residue that does not contain a side chain. In some embodiments, (Xaa) a7 is or includes a residue whose side chain is MetO2 (methionine sulfone), D, R, A, or the side chain of Y. In some embodiments, (Xaa) a7 is or includes a residue whose side chain is the side chain of D, R, A, or Y. In some embodiments, (Xaa) a7 is or includes a residue whose side chain is the side chain of D, R, or S. In some embodiments, (Xaa) a7 is or includes a residue that is a side chain of D, E, N, or Q. In some embodiments, (Xaa) a7 is or includes a residue of MetO2, D, A, G, R, or Y. In some embodiments, (Xaa) a7 is or includes a residue of D, A, G, R, or Y. In some embodiments, (Xaa) a7 is or includes a residue of D, E, N, or Q. In some embodiments, (Xaa) a7 is or includes a residue of D, G, R, or S. In some embodiments, (Xaa) a7 is or includes G. In some embodiments, (Xaa) a7 In some embodiments, (Xaa) is or includes MetO2. a7 is or includes A. In some embodiments, (Xaa) a7 is or includes D. In some embodiments, (Xaa) a7is or includes E. In some embodiments, (Xaa) a7 is or includes Q. In some embodiments, (Xaa) a7 is or includes N. In some embodiments, (Xaa) a7 is or includes R. In some embodiments, (Xaa) a7 is or includes S. In some embodiments, a7 is 1.

[0146] In some embodiments, (Xaa) a8 is or comprises a residue comprising a hydrophobic side chain. a8 is or comprises a residue containing an aliphatic side chain. In some embodiments, (Xaa) a8 is or includes a residue whose side chain is a side chain of V, D, G, W, S, T, or A. In some embodiments, (Xaa) a8 is or includes a residue of V, D, G, W, S, T, or A. In some embodiments, (Xaa) a8 is or includes V. In some embodiments, (Xaa) a8 is or includes D. In some embodiments, (Xaa) a8 is or includes G. In some embodiments, (Xaa) a8 is or includes W. In some embodiments, (Xaa) a8 is or includes S. In some embodiments, (Xaa) a8 In some embodiments, a is or includes T. In some embodiments, a is or includes A. In some embodiments, a is 1.

[0147] In some embodiments, a9 is 1. In some embodiments, (Xaa) a9 is Xaa as described herein T3 is.

[0148] In some embodiments, a10 is 1. In some embodiments, (Xaa) a10 is Xaa as described herein T4 is.

[0149] In some embodiments, a11 is 1. In some embodiments, (Xaa) a11 is Xaa as described herein T5 is.

[0150] In some embodiments, (Xaa) a12 is or comprises a residue containing a polar or charged side chain. a12 is or includes a residue that does not contain a side chain. In some embodiments, (Xaa) a12 is or comprises a residue comprising a hydrophobic side chain. a12 is or includes a residue whose side chain is the side chain of D, S, G, Ahp, or A. In some embodiments, (Xaa) a12 is or includes a residue of D, S, G, Ahp, or A. In some embodiments, (Xaa) a12 is or includes D. In some embodiments, (Xaa) a12 is or includes S. In some embodiments, (Xaa) a12 is or includes G. In some embodiments, (Xaa) a12 In some embodiments, (Xaa) is or includes Ahp. a12 is or includes A. In some embodiments, a12 is 1.

[0151] In some embodiments, (Xaa) a13 is or comprises a residue whose side chain contains a nucleophile. a13 is or comprises a residue whose side chain comprises -S-. In some embodiments, (Xaa) a13is or includes a residue whose side chain is the side chain of C. In some embodiments, (Xaa) a13 is or comprises a residue of C. In some embodiments, a13 is 1. In some embodiments, a13 is greater than 1 and the final residue is a residue whose side chain comprises a nucleophile (e.g., C) as described herein. In some embodiments, (Xaa) a13 (e.g., the C-terminal residue) of a1 In some embodiments, it is linked to a linker (e.g., a Xaa, C-terminal residue, etc.) of L as described herein. T ) for example, in some embodiments, a linker connects a C-terminal residue to an N-terminal cysteine ​​via its -S- group through its amino group (e.g., in the case of -C(O)-CH-, -C(O)- is attached to the amino group and -CH- is attached to -S-). In some embodiments, a linker connects a residue whose side chain includes -S- group (e.g., of a C residue) to the amino group of another residue (e.g., in the case of -C(O)-CH-, -C(O)- is attached to the amino group and -CH- is attached to -S-).

[0152] Exemplary sequences and their data include those set forth below: [Table 2] [Table 3]

[0153] In some embodiments, the target binding moiety or [ka] are as described above and / or as utilized in the compounds of Table 1. [ka] teeth, [ka] or a salt form thereof. [ka] teeth, [ka] or a salt form thereof. [ka] teeth, [ka] or a salt form thereof. [ka] teeth, [ka] or a salt form thereof. [ka] teeth, [ka] or a salt form thereof. [ka] teeth, [ka] or a salt form thereof.

[0154] In some embodiments, -(Xaa)y- is -Xaa T6-(Xaa)y'-Xaa T7 -Xaa T8 -Xaa T9 -Xaa T10 -Xaa T11 - is or contains During the ceremony, y' is 0 to 8, Xaa T6 is a residue of an amino acid or amino acid analogue in which the side chain is substituted with a C1-C8 aliphatic group, Xaa T7 is a residue of an amino acid or amino acid analog whose side chain is an optionally substituted C2-C8 aliphatic; Xaa T8 is a residue of proline or an amino acid analog thereof, Xaa T9 is a residue of an amino acid or amino acid analogue whose side chain contains an optionally substituted aromatic group or is optionally substituted C1-C8 aliphatic; Xaa T10 is a residue of a C1-C8 aliphatic amino acid or amino acid analogue having a substituted side chain, or a residue of an amino acid having a substituted amino group; Xaa T11 is a residue of an amino acid or amino acid analog whose side chain contains an optionally substituted aromatic group or is optionally substituted C1-C8 aliphatic.

[0155] In some embodiments, y' is 0. In some embodiments, y' is 1. In some embodiments, y' is 2. In some embodiments, y' is 3. In some embodiments, y' is 4. In some embodiments, y' is 5. In some embodiments, y' is 6. In some embodiments, y' is 7. In some embodiments, y' is 8.

[0156] In some embodiments, Xaa T6 is a residue comprising a hydrophobic side chain. T6is a residue comprising a C1-C8 aliphatic side chain substituted. In some embodiments, the side chain is -CH2-R, where -CH2- is optionally substituted and R is an optionally substituted aryl or heteroaryl. In some embodiments, R is phenyl. In some embodiments, the side chain is -CH2Ph. In some embodiments, Xaa T6 is an amino acid residue, the amino group of which is substituted. In some embodiments, the amino group is -N(R')-. In some embodiments, R' is an optionally substituted C1-C6 alkyl. In some embodiments, R' is methyl. In some embodiments, the side chain is the side chain of MeF (F, where a methyl group is present on N(-N(Me)-), L, or S). In some embodiments, Xaa T6 is N(Me)-CH(CHPh)-C(O)-. In some embodiments, Xaa T6 is a residue of MeF, L, or S.

[0157] In some embodiments, Xaa T7 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T7 The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T7 The side chain of Xaa is or comprises an optionally substituted C3-C8 alkyl. T7 The side chain of Xaa is or comprises an optionally substituted C4-C8 alkyl. T7 The side chain of Xaa is or comprises an optionally substituted C3-C8 branched alkyl. T7 The side chain of Xaa is or comprises an optionally substituted C4-C8 branched alkyl. T7 The side chain of Xaa is a branched C3-C8 alkyl. T7is a branched C4-C8 alkyl. In some embodiments, the side chain is (CH3)2CHCH2-. In some embodiments, the side chain is the side chain of L. In some embodiments, Xaa T7 is the residue of L.

[0158] In some embodiments, Xaa T8 is a residue that includes the cyclic portion involved in the backbone. T8 is P.

[0159] In some embodiments, Xaa T9 is or includes an aromatic group. T9 is -CH2-R, where -CH2- is optionally substituted and R is as described herein. In some embodiments, R is an optionally substituted aryl or heteroaryl. In some embodiments, R is a substituted phenyl. In some embodiments, R is 4-hydroxyphenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, the side chain is the side chain of Bph. In some embodiments, Xaa T9 is a residue of Bph. T9 comprises a substituted C1-C8 aliphatic. In some embodiments, the substitution is a polar or charged group such as -OH, -COOH, etc. In some embodiments, the side chain is a D or S side chain. In some embodiments, Xaa T9 is a D or S residue.

[0160] In some embodiments, Xaa T10 The side chain of Xaa is or comprises a substituted C1-C8 aliphatic. T10 The side chain of Xaa is or comprises an optionally substituted C2-C8 aliphatic. T10 The side chain of Xaa is or comprises an optionally substituted C2-C8 alkyl. T10The side chain of Xaa is C2-C8 alkyl. T10 The side chain of Xaa is or comprises an optionally substituted straight chain C2-C8 alkyl. T10 The side chain of Xaa is a straight chain C2-C8 alkyl. T10 The side chain of Xaa is or comprises an optionally substituted branched C3-C8 alkyl. T10 The side chain of Xaa is a branched C3-C8 alkyl. In some embodiments, the side chain is (CH3)2CH-. In some embodiments, the side chain is (CH3)2CHCH2-. In some embodiments, Xaa T10 is a residue of V. In some embodiments, Xaa T10 is a residue of L. In some embodiments, Xaa T10 is an amino acid residue, the amino group of which is substituted. In some embodiments, the amino group is -N(R')-. In some embodiments, R' is an optionally substituted C1-C6 alkyl. In some embodiments, R' is methyl. In some embodiments, Xaa T10 In some embodiments, Xaa has no side chain. T10 is -N(Me)-CH2-C(O)-.

[0161] In some embodiments, Xaa T11 is or includes an aromatic group. T11 The side chain of is -CH2-R, where -CH2- is optionally substituted and R is as described herein. In some embodiments, R is an optionally substituted aryl or heteroaryl. In some embodiments, R is a substituted phenyl. In some embodiments, R is 4-hydroxyphenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, R is an optionally substituted [ka] In some embodiments, R is [ka] In some embodiments, the side chain is the side chain of W. In some embodiments, Xaa T11 is a residue of W. In some embodiments, Xaa T11 comprises a substituted C1-C8 aliphatic. In some embodiments, the substitution is a polar or charged group such as -OH, -COOH, etc. In some embodiments, the side chain is positively charged. In some embodiments, the side chain is the side chain of R. In some embodiments, Xaa T11 is the residue of R.

[0162] In some embodiments, Xaa T6 is a residue of MeF. T7 is a residue of L. In some embodiments, Xaa T8 is a residue of P. In some embodiments, Xaa T9 is a residue of Bph. T10 is a residue of V. In some embodiments, Xaa T11 is the residue of W.

[0163] In some embodiments, -(Xaa)y- is -(Xaa) a1 -(Xaa) a2 -(Xaa) a3 -(Xaa) a4 -(Xaa) a5 -(Xaa) a6 -(Xaa) a7 -(Xaa) a8 -(Xaa) a9 -(Xaa) a10 -(Xaa) a11 -(Xaa) a12 - is or contains During the ceremony, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and a12 each independently represent an integer of 0 to 5; (Xaa) a4 is Xaa T6is or contains (Xaa) a6 is Xaa T7 is or contains (Xaa) a7 is Xaa T8 is or contains (Xaa) a8 is Xaa T9 is or contains (Xaa) a9 is Xaa T10 is or contains (Xaa) a10 is Xaa T11 is or contains

[0164] In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and / or a12 are independently 0. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and / or a12 are independently 1. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and / or a12 are independently 2. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and / or a12 are independently 3. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and / or a12 are independently 4. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and / or a12 are independently 5. In some embodiments, a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and a12 are 1.

[0165] In some embodiments, (Xaa) a1 is or includes A. In some embodiments, a1 is 1 and (Xaa) a1 is a residue of A. In some embodiments, a1 is 0. In some embodiments, (Xaa)a1 The Xaa (e.g., the N-terminal residue) of (Xaa) can be replaced by another Xaa described herein (e.g., (Xaa) a13 Xaa of the N-terminal residue, Xaa of the C-terminal residue, etc. For example, in some embodiments, a linker links the N-terminal residue through its amino group to the C-terminal cysteine ​​through its -S- (e.g., in the case of -C(O)-CH-, -C(O)- is bonded to the amino group and -CH- is bonded to -S-).

[0166] In some embodiments, (Xaa) a2 is Xaa containing a hydrophobic side chain H In some embodiments, Xaa is or comprises a residue. In some embodiments, the side chain is -CH. In some embodiments, the side chain is (CH)CHCH-. In some embodiments, Xaa is a residue of L. In some embodiments, Xaa is a residue of A. In some embodiments, Xaa is a residue of P. In some embodiments, (Xaa) a2 is or includes L. In some embodiments, (Xaa) a2 is or includes A. In some embodiments, (Xaa) a2 is or comprises P. In some embodiments, a2 is 1.

[0167] In some embodiments, Xaa HThe side chain of comprises a substituted C1-C8 aliphatic. In some embodiments, the side chain is or comprises an optionally substituted C2-C8 aliphatic. In some embodiments, the side chain is or comprises an optionally substituted C2-C8 alkyl. In some embodiments, the side chain is or comprises an optionally substituted C3-C8 alkyl. In some embodiments, the side chain is or comprises an optionally substituted C4-C8 alkyl. In some embodiments, the side chain is or comprises an optionally substituted C3-C8 branched alkyl. In some embodiments, the side chain is or comprises an optionally substituted C4-C8 branched alkyl. In some embodiments, the side chain is a branched C3-C8 alkyl. In some embodiments, the side chain is a branched C4-C8 alkyl. In some embodiments, the side chain is methyl. In some embodiments, the side chain is (CH3)2CHCH2-. In some embodiments, Xaa H is a residue of L. In some embodiments, Xaa H is the residue of A.

[0168] In some embodiments, (Xaa) a3 is or comprises a residue comprising a basic side chain (positively charged side chain). In some embodiments, the side chain of Xaa comprises an optionally substituted aromatic basic moiety. In some embodiments, the side chain comprises an optionally substituted imidazolyl. In some embodiments, the side chain of Xaa comprises an optionally substituted non-aromatic basic moiety. In some embodiments, the side chain comprises an optionally substituted guanidinyl. In some embodiments, the side chain comprises an optionally substituted amino. Other types of residues, such as residues comprising hydrophobic aliphatic side chains (e.g., A), can also be utilized. In some embodiments, the side chain is the side chain of H. In some embodiments, the side chain is the side chain of R. In some embodiments, the side chain is the side chain of A. In some embodiments, Xaa is a residue of H. In some embodiments, Xaa is a residue of R. In some embodiments, (Xaa) a3 is Xaa as described herein HIn some embodiments, Xaa is or comprises a residue of A. In some embodiments, (Xaa) a3 is or includes H. In some embodiments, (Xaa) a3 is or includes R. In some embodiments, (Xaa) a3 is or includes A. In some embodiments, a3 is 1.

[0169] In some embodiments, (Xaa) a4 is Xaa T6 In some embodiments, a4 is or comprises 1. In some embodiments, (Xaa) a4 is Xaa as described herein T6 In some embodiments, (Xaa) a4 is a residue of MeF or L. In some embodiments, (Xaa) a4 In some embodiments, (Xaa) is or comprises MeF. a4 is or includes L. In some embodiments, a4 is 1.

[0170] In some embodiments, (Xaa) a5 is Xaa H In some embodiments, (Xaa) a5 is or comprises Xaa, the side chain of which is or comprises a substituted C1-C8 aliphatic. In some embodiments, the side chain is methyl. In some embodiments, Xaa is any of the Xaa groups described herein. T10 In some embodiments, Xaa is a residue of V. In some embodiments, Xaa is a residue of A. In some embodiments, Xaa is a residue of MeG (methyl on amino group). In some embodiments, (Xaa) a5 is or includes V. In some embodiments, (Xaa) a5 is or includes A. In some embodiments, (Xaa) a5In some embodiments, a5 is 1.

[0171] In some embodiments, (Xaa) a6 is (Xaa) as described herein a2 In some embodiments, (Xaa) a6 is Xaa containing a hydrophobic side chain H In some embodiments, Xaa is or comprises a residue. In some embodiments, the side chain is -CH. In some embodiments, the side chain is (CH)CHCH-. In some embodiments, Xaa is a residue of L. In some embodiments, Xaa is a residue of A. In some embodiments, Xaa is a residue of P. In some embodiments, (Xaa) a6 is or includes L. In some embodiments, (Xaa) a6 is or includes A. In some embodiments, (Xaa) a6 is or includes P. In some embodiments, a6 is 1.

[0172] In some embodiments, (Xaa) a6 is Xaa T7 In some embodiments, a6 is 1. In some embodiments, (Xaa) a6 is Xaa as described herein T7 In some embodiments, (Xaa) a6 is a residue of L or P.

[0173] In some embodiments, (Xaa) a7 is Xaa T8 In some embodiments, a7 is or comprises 1. In some embodiments, (Xaa) a7 is Xaa as described herein T8 In some embodiments, (Xaa) a7 is the residue of P.

[0174] In some embodiments, (Xaa) a8 is XaaT9 In some embodiments, a8 is or comprises 1. In some embodiments, (Xaa) a8 is Xaa as described herein T9 In some embodiments, (Xaa) a8 is a residue of Bph. In some embodiments, (Xaa) a8 is a D or S residue.

[0175] In some embodiments, (Xaa) a9 is Xaa T10 In some embodiments, a9 is 1. In some embodiments, (Xaa) a9 is Xaa as described herein T10 In some embodiments, (Xaa) a9 is a residue of V, L, or MeG.

[0176] In some embodiments, (Xaa) a10 is Xaa T11 In some embodiments, a10 is 1. In some embodiments, (Xaa) a10 is Xaa as described herein T11 In some embodiments, (Xaa) a10 is a residue of W or R.

[0177] In some embodiments, (Xaa) a11 is Xaa H In some embodiments, (Xaa) a11 is or includes Xaa, the side chain of which is or includes an optionally substituted C1-C8 aliphatic. In some embodiments, the side chain is methyl. In some embodiments, the side chain is isopropyl. In some embodiments, Xaa is any of the Xaa groups described herein. T10In some embodiments, Xaa is a residue of V. In some embodiments, Xaa is a residue of V. In some embodiments, Xaa is a residue of A. In some embodiments, Xaa is a residue of MeG (methyl on amino group). In some embodiments, (Xaa) a11 is or includes V. In some embodiments, (Xaa) a11 is or includes A. In some embodiments, (Xaa) a11 In some embodiments, a11 is 1.

[0178] In some embodiments, (Xaa) a12 is or comprises a residue whose side chain contains a nucleophile. a12 is or comprises a residue whose side chain comprises -S-. In some embodiments, (Xaa) a12 is or includes a residue whose side chain is the side chain of C. In some embodiments, (Xaa) a12 is or includes a residue of C. In some embodiments, a12 is 1. In some embodiments, a12 is greater than 1 and the final residue is a residue whose side chain includes a nucleophile (e.g., C) as described herein. In some embodiments, (Xaa) a12 (e.g., the C-terminal residue) of a1 Xaa of a C-terminal residue, such as Xaa of a C-terminal residue (e.g., the C-terminal residue). For example, in some embodiments, a linker links the C-terminal residue through its -S- to the N-terminal cysteine ​​through its amino group (e.g., in the case of -C(O)-CH-, -C(O)- is attached to the amino group and -CH- is attached to -S-). In some embodiments, a linker links a residue whose side chain includes -S- (e.g., in the case of -C(O)-CH-), to the amino group of another residue (e.g., in the case of -C(O)-CH-, -C(O)- is attached to the amino group and -CH- is attached to -S-).

[0179] Exemplary sequences and their data include those set forth below: [Table 4] [Table 5]

[0180] In some embodiments, the target binding moiety or [ka] are those described above and / or utilized in the compounds of Table 1. [ka] teeth, [ka] or a salt form thereof. [ka] teeth, [ka] or a salt form thereof.

[0181] In some embodiments, the target binding moiety or [ka] or -(Xaa)y- is or comprises a peptide that is: (1) A polypeptide having an amino acid sequence represented by any one of SEQ ID NOs: 1 to 34; [Table 6-1] [Table 6-2] (2) A polypeptide having an amino acid sequence represented by any one of SEQ ID NOs: 1 to 34, in which the N-terminal amino acid residue is chloroacetylated (e.g., at its amino group); (3) A polypeptide having an amino acid sequence having a deletion, addition, substitution, or insertion of any one of amino acids in SEQ ID NOs: 1 to 34, but not including an amino acid sequence having a deletion of Cys at the C-terminus of SEQ ID NOs: 1 to 34. (4) A polypeptide having an amino acid sequence represented by any one of SEQ ID NOs: 1 to 34, which has a deletion, addition, substitution, or insertion of an amino acid in any one of SEQ ID NOs: 1 to 34, but does not contain an amino acid sequence having a deletion of a C-terminal Cys in any one of SEQ ID NOs: 1 to 34, and in which the N-terminal amino acid is chloroacetylated (e.g., at its amino group); or (5) The polypeptide according to any one of (1) to (4) above, wherein the polypeptide has a cyclized structure.

[0182] In some embodiments, the target binding moiety or [ka] or -(Xaa)y- is or comprises a peptide that is: (1) The amino acid sequence represented by SEQ ID NO: 1 or 2: Ala Arg Ahp Tyr His Asp Gly Val Leu Bph Ahp Asp Cys (SEQ ID NO: 1), A polypeptide having Ala Leu His MePhe Val Leu Pro Bph Val Trp Val Cys (SEQ ID NO: 2), (2) A polypeptide having the amino acid sequence represented by SEQ ID NO: 1 or 2, in which the N-terminal Ala is chloroacetylated Ala; (3) A polypeptide having an amino acid sequence having one or more amino acid deletions, additions, substitutions or insertions of SEQ ID NO: 1 or 2, but not including an amino acid sequence having a deletion of Cys at the C-terminus of SEQ ID NO: 1 or 2; (4) A polypeptide having the amino acid sequence represented by SEQ ID NO: 1 or 2, in which the N-terminal Ala is chloroacetylated Ala, and which does not contain an amino acid sequence having a deletion of C-terminal Cys of SEQ ID NO: 1 or 2, in which one or more amino acids of SEQ ID NO: 1 or 2 are deleted, added, substituted, or inserted; or (5) The polypeptide according to any one of (1) to (4) above, wherein the polypeptide has a cyclized structure.

[0183] In some embodiments, an amino acid residue, e.g., an N-terminal amino acid residue (e.g., Ala), is connected to Cys via -C(O)-CH2-, where -C(O)- is attached to the amino group of Ala and -CH2- is attached to -S- of Cys. In some embodiments, the N-terminal amino acid residue, such as Ala, is attached by reacting a chloroacetylated amino acid residue, such as Ala, with -SH of Cys under suitable conditions.

[0184] In some embodiments, the amino acid substitutions are conservative substitutions. In some embodiments, the substitutions do not significantly affect the structure, properties, and / or activity of the peptide and / or protein. In some embodiments, examples of amino acid groups with side chains having similar chemical properties include: 1) aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine; 2) aliphatic hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine, and tryptophan; 5) basic side chains: lysine, arginine, and histidine; 6) acidic side chains: aspartic acid and glutamic acid; and 7) sulfur-containing side chains: cysteine ​​and methionine. In some embodiments, the conservative amino acid substitutions are selected from valine-leucine-isoleucine, phenylalanine-tyrosine-tryptophan, lysine-arginine, alanine-valine, glutamic acid-aspartic acid, and asparagine-glutamine. The aforementioned amino acids may be proteinogenic or non-proteinogenic amino acids. Those skilled in the art will appreciate that, depending on the circumstances, amino acids may be grouped based on structure, properties, activity, etc. in other ways suitable for the intended purpose. In some embodiments, the present disclosure provides a target-binding moiety, which is or comprises an amino acid sequence represented by one of SEQ ID NOS: 1-34, with deletion, substitution, insertion, and / or addition of 1 to 5 amino acids, preferably 4 or less, 3 or less, 2 or less, and more preferably 1 or less amino acids, and is capable of binding to CD38.

[0185] In some embodiments, the target binding moiety or [ka] is or comprises a sequence represented by one of SEQ ID NOs: 1 to 34. In some embodiments, the target binding moiety is or comprises a cyclized structure.

[0186] In some embodiments, the target binding moiety is a structure selected from the following S-1 to S-32 (amino acid sequence SEQ ID NOs are provided), or a pharmaceutically acceptable salt thereof: [ka] is or is derived from: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0187] In some embodiments, the target binding moiety is a structure selected from the following S-33 to S-39 (amino acid sequence SEQ ID NOs are provided), or a pharmaceutically acceptable salt thereof: [ka] is or is derived from: [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0188] Among them, various structures (e.g., S-1 to S-39) have been evaluated in various assays and shown to bind to CD38.

[0189] As will be appreciated by those skilled in the art, the structures (e.g., S-1 through S-39) may be connected to the remainder of the molecule (e.g., the antibody binding moiety, optionally via a linker) via any suitable method according to the present disclosure (e.g., via a side chain, such as a particular amino side group, the N-terminus, the C-terminus, etc.).

[0190] In some embodiments, the peptide unit, e.g., [ka] or a salt thereof, comprises a functional group on an amino acid residue that can react with a functional group on another amino acid residue. In some embodiments, a peptide unit comprises an amino acid residue having a side chain that comprises a functional group that can react with another functional group on the side chain of another amino acid residue to form a linkage (see, e.g., Table A-1, Table 1, etc.). In some embodiments, a functional group on one amino acid residue is connected to a functional group on another amino acid residue to form a linkage (or bridge). The linkage is attached to a backbone atom of the peptide unit, but does not include a backbone atom. In some embodiments, a peptide unit comprises a linkage formed by two side chains of non-adjacent amino acid residues. In some embodiments, the linkage is attached to two backbone atoms of two non-adjacent amino acid residues. In some embodiments, both backbone atoms attached to the linkage are carbon atoms. In some embodiments, the linkage is b It has the structure of L b is the L described in this disclosure a and L a is not a covalent bond. a In some embodiments, L a In some embodiments, -Cy- includes -Cy-, where -Cy- is an optionally substituted heteroaryl. [ka] In some embodiments, L a teeth, [ka] In some embodiments, such L a can be formed by the -N3 group of the side chain of one amino acid residue and the -≡- of the side chain of another amino acid residue. In some embodiments, the linkage is formed through the connection of two thiol groups (e.g., two cysteine ​​residues). In some embodiments, L a In some embodiments, L ais -CH2-SS-CH2-. In some embodiments, the linkage is formed through the connection of an amino group (e.g., -NH2 of the side chain of a lysine residue) and a carboxylic acid group (e.g., -COOH of the side chain of an aspartic acid or glutamic acid residue). In some embodiments, L a In some embodiments, L a In some embodiments, L a is -CHCONH-(CH)-. In some embodiments, L a comprises —C(O)—N(R′)—, where R′ is R, and together with the R groups on the peptide backbone form a ring (e.g., A-34). a is —(CH)—N(R′)—CO—(CH). In some embodiments, —Cy- is optionally substituted phenylene. In some embodiments, —Cy- is optionally substituted 1,2-phenylene. In some embodiments, L a teeth, [ka] In some embodiments, L a teeth, [ka] In some embodiments, L a is an optionally substituted divalent C 2-20 In some embodiments, L a is optionally substituted -(CH2)9-CH=CH-(CH2)9-. In some embodiments, L a is -(CH2)3-CH=CH-(CH2)3-.

[0191] In some embodiments, the two amino acid residues joined at the linkage are separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more than 15 amino acid residues between them (excluding the two amino acid residues joined at the linkage). In some embodiments, the number is 1. In some embodiments, the number is 2. In some embodiments, the number is 3. In some embodiments, the number is 4. In some embodiments, the number is 5. In some embodiments, the number is 6. In some embodiments, the number is 7. In some embodiments, the number is 8. In some embodiments, the number is 9. In some embodiments, the number is 10. In some embodiments, the number is 11. In some embodiments, the number is 12. In some embodiments, the number is 13. In some embodiments, the number is 14. In some embodiments, the number is 15.

[0192] In some embodiments, the target-binding moiety comprises a peptide unit, and the antibody-binding moiety is connected to a backbone atom of the peptide unit, optionally via a linker. In some embodiments, the target-binding moiety comprises a peptide unit, and the antibody-binding moiety is connected to a side chain atom or group of an amino acid residue of the peptide unit, optionally via a linker. For example, in some embodiments, the antibody-binding moiety is connected via a side chain atom -SH, -OH, -COOH, or -NH2.

[0193] amino acid In some embodiments, provided compounds and agents may include one or more amino acid moieties, for example, in universal antibody binding moieties, linker moieties, etc. The amino acid moieties may be either naturally occurring amino acid or unnatural amino acid moieties. In some embodiments, the amino acid has the structure of formula AI: NH(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 -COOH, AI or a salt thereof, wherein each variable is independent as described in this disclosure. In some embodiments, an amino acid residue, e.g., an amino acid residue having the structure of formula AI, is selected from the group consisting of -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 In some embodiments, each amino acid residue of the peptide independently has the structure -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 It has the structure -CO-.

[0194] In some embodiments, L a1 is a covalent bond. In some embodiments, the compound of formula AI has the structure NH(R a1 )-C(R a2 )(R a3 )-L a2 In some embodiments, L a2 is -CH2SCH2-.

[0195] In some embodiments, L a2 is a covalent bond. In some embodiments, the compound of formula AI has the structure NH(R a1 )-L a1 -C(R a2 )(R a3 In some embodiments, the amino acid residue is a compound of the formula -N(R a1 )-L a1 -C(R a2 )(R a3 In some embodiments, L a1 is -CH2CH2S-. In some embodiments, L a1 is -CH2CH2S-, where CH2 is NH(R a1 )

[0196] In some embodiments, L a1 is a covalent bond, and L a2is a covalent bond. In some embodiments, the compound of formula AI has the structure NH(R a1 )-C(R a2 )(R a3 In some embodiments, the compound of formula AI is a compound of the structure NH(R a1 )-CH(R a2 In some embodiments, the compound of formula AI is a compound of the structure NH(R a1 )-CH(R a3 )-COOH. In some embodiments, the compound of formula AI has the structure NH—CH(R a2 )-COOH. In some embodiments, the compound of formula AI has the structure NH—CH(R a3 In some embodiments, the amino acid residue is a compound of the formula -N(R a1 )-C(R a2 )(R a3 In some embodiments, the amino acid residue has the structure -N(R a1 )-CH(R a2 In some embodiments, the amino acid residue has the structure -N(R a1 )-CH(R a3 In some embodiments, the amino acid residue has the structure -NH-CH(R a2 In some embodiments, the amino acid residue has the structure -NH-CH(R a3 )-CO- structure.

[0197] In some embodiments, L a is a covalent bond. In some embodiments, L a is an optionally substituted C 1-6 In some embodiments, L a is an optionally substituted C 1-6 In some embodiments, L is alkylene. a is -CH-. In some embodiments, L a is -CHCH-. In some embodiments, L a is -CH2CH2CH2-.

[0198] In some embodiments, R' is R. In some embodiments, R a1 is R, and R is as described in this disclosure. In some embodiments, R a1 is R and R is methyl. In some embodiments, R a2 is R, and R is as described in this disclosure. In some embodiments, R a3 is R, and R is as described in this disclosure. In some embodiments, R a1 , R a2 , and R a3 Each of is independently R, where R is as described in this disclosure.

[0199] In some embodiments, R a1 is hydrogen. In some embodiments, R a2 is hydrogen. In some embodiments, R a3 is hydrogen. In some embodiments, R a1 is hydrogen and R a2 and R a3 In some embodiments, at least one of R a1 is hydrogen and R a2 and R a3 is hydrogen and the other is not hydrogen. a2 -L a -R and R a3 is —H. In some embodiments, R a3 -L a -R and R a2 is —H. In some embodiments, R a2 is -CH2-R, and R a3 is —H. In some embodiments, R a3 is -CH2-R, and R a2 is —H. In some embodiments, R a2 is R and R a3 is —H. In some embodiments, R a3 is R and R a2 is -H.

[0200] In some embodiments, R a2 -L a -R, where R is as described in this disclosure. In some embodiments, R a2 -L a -R, where R is C 3-30 Alicyclic, C 5-30 In some embodiments, R is a substituent selected from aryl, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a2 -L a -R, where R is C 6-30 In some embodiments, R is a substituent selected from aryl and 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a2 is the side chain of an amino acid. In some embodiments, R a2 is the side chain of a standard amino acid.

[0201] In some embodiments, R a3 -L a -R, where R is as described in this disclosure. In some embodiments, R a3 -L a -R, where R is C 3-30 Alicyclic, C 5-30 In some embodiments, R is a substituent selected from aryl, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a3 -L a -R, where R is C 6-30In some embodiments, R is a substituent selected from aryl and 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. a3 is the side chain of an amino acid. In some embodiments, R a3 is the side chain of a standard amino acid.

[0202] In some embodiments, R is optionally substituted C 1-6 In some embodiments, R is an optionally substituted C 1-6 In some embodiments, R is alkyl. In some embodiments, R is -CH. In some embodiments, R is optionally substituted pentyl. In some embodiments, R is n-pentyl.

[0203] In some embodiments, R is a cyclic group. In some embodiments, R is an optionally substituted C 3-30 In some embodiments, R is cyclopropyl.

[0204] In some embodiments, R is an optionally substituted aromatic group and the amino acid residue of the amino acid of formula AI is Xaa A In some embodiments, R a2 or R a3 is -CH2-R, where R is an optionally substituted aryl or heteroaryl group. In some embodiments, R is substituted phenyl. In some embodiments, R is phenyl. In some embodiments, R is substituted phenyl. In some embodiments, R is 4-trifluoromethylphenyl. In some embodiments, R is 4-phenylphenyl. In some embodiments, R is an optionally substituted 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is an optionally substituted 5-14 membered heteroaryl having 1-5 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, R is [ka] In some embodiments, R is a substituted pyridinyl. In some embodiments, R is 1-pyridinyl. In some embodiments, R is 2-pyridinyl. In some embodiments, R is 3-pyridinyl. In some embodiments, R is [ka] is.

[0205] In some embodiments, R' is -COOH. In some embodiments, the compound and amino acid residue of the amino acid of formula AI is Xaa N is.

[0206] In some embodiments, R' is NH2. In some embodiments, the compound of the amino acid residue of the amino acid of formula AI is Xaa P is.

[0207] In some embodiments, R a2 or R a3 is R, and R is a C 1-20 In some embodiments, the compound of amino acid residues of the amino acid of formula AI is Xaa H In some embodiments, R is -CH3. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is n-propyl. In some embodiments, R is butyl. In some embodiments, R is n-butyl. In some embodiments, R is pentyl. In some embodiments, R is n-pentyl. In some embodiments, R is cyclopropyl.

[0208] In some embodiments, R a1 , R a2 , and R a3 and two or more of are R and taken together form an optionally substituted ring as described in this disclosure.

[0209] In some embodiments, R a1 and R a2 and R a3 One of them is R, and together they form R a1 forms an optionally substituted 3- to 6-membered ring with no additional ring heteroatoms other than the nitrogen atom to which it is attached. In some embodiments, the ring formed is a 5-membered ring, such as proline.

[0210] In some embodiments, R a2 and R a3 is R and taken together form an optionally substituted 3-6 membered ring as described in this disclosure. In some embodiments, R a2 and R a3 is R and taken together form an optionally substituted 3-6 membered ring having one or more nitrogen ring atoms. In some embodiments, R a2 and R a3 is R and together form an optionally substituted 3- to 6-membered ring having one ring heteroatom that is a nitrogen atom and up to one ring heteroatom. In some embodiments, the ring is a saturated ring.

[0211] In some embodiments, the amino acid is a natural amino acid. In some embodiments, the amino acid is an unnatural amino acid. In some embodiments, the amino acid is an alpha amino acid. In some embodiments, the amino acid is a beta amino acid. In some embodiments, the compound of formula AI is a natural amino acid. In some embodiments, the compound of formula AI is an unnatural amino acid.

[0212] In some embodiments, the amino acid comprises a hydrophobic side chain. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, L, M, F, Y, or W. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, L, M, or F. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, L, or M. In some embodiments, the amino acid with a hydrophobic side chain is A, V, I, or L. In some embodiments, the hydrophobic side chain is R, where R is C. 1-10 In some embodiments, R is C 1-10 In some embodiments, R is alkyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is butyl. In some embodiments, R is pentyl. In some embodiments, R is n-pentyl. In some embodiments, the amino acid having a hydrophobic side chain is NHCH(CHCHCHCHCHCH)COOH. In some embodiments, the amino acid having a hydrophobic side chain is (S)-NHCH(CHCHCHCHCHCH)COOH. In some embodiments, the amino acid having a hydrophobic side chain is (R)-NHCH(CHCHCHCHCHCH)COOH. In some embodiments, the hydrophobic side chain is -CHR, and R is an optionally substituted phenyl. In some embodiments, R is phenyl. In some embodiments, R is phenyl substituted with one or more hydrocarbon groups. In some embodiments, R is 4-phenylphenyl. In some embodiments, an amino acid having a hydrophobic side chain is NHCH(CH-4-phenylphenyl)COOH. In some embodiments, an amino acid having a hydrophobic side chain is (S)-NHCH(CH-4-phenylphenyl)COOH. In some embodiments, an amino acid having a hydrophobic side chain is (R)-NHCH(CH-4-phenylphenyl)COOH.

[0213] In some embodiments, the amino acid comprises a positively charged side chain as described herein (e.g., at physiological pH). In some embodiments, such amino acids comprise a basic nitrogen in their side chain. In some embodiments, such amino acids are Arg, His, or Lys. In some embodiments, such amino acids are Arg. In some embodiments, such amino acids are His. In some embodiments, such amino acids are Lys.

[0214] In some embodiments, the amino acid comprises a negatively charged side chain as described herein (e.g., at physiological pH). In some embodiments, the amino acid comprises a -COOH in its side chain. In some embodiments, the amino acid is Asp. In some embodiments, the amino acid is Glu.

[0215] In some embodiments, the amino acid comprises a side chain comprising an aromatic group as described herein. In some embodiments, the amino acid is Phe, Tyr, Trp, or His. In some embodiments, the amino acid is Phe. In some embodiments, the amino acid is Tyr. In some embodiments, the amino acid is Trp. In some embodiments, the amino acid is His. In some embodiments, the amino acid is NH2-CH(CH2-4-phenylphenyl)-COOH. In some embodiments, the amino acid is (S)-NH2-CH(CH2-4-phenylphenyl)-COOH. In some embodiments, the amino acid is (R)-NH2-CH(CH2-4-phenylphenyl)-COOH.

[0216] In some embodiments, the amino acid is a known proteinogenic amino acid that is naturally encoded or found in the genetic code of any organism, or a non-proteinogenic amino acid that is not naturally encoded or found in the genetic code of any organism. Examples of non-proteinogenic amino acids include α,α-disubstituted amino acids (such as α-methylalanine), N-alkyl-α-amino acids and N-alkyl-α-D-amino acids, and amino acids whose main chain structure may differ from that of natural amino acids. Examples of such amino acids include β-amino acids and amino acids with side chain structures that differ from those of natural amino acids (such as norleucine, homohistidine, and hydroxyproline).

[0217] In some embodiments, the amino acid is selected from the following: [Table 7]

[0218] target In some embodiments, the present disclosure provides techniques for selectively directing agents comprising target-binding moieties (e.g., ARM compounds), antibodies, and immune cells (e.g., NK cells) to desired target sites comprising one or more targets. As will be appreciated by those skilled in the art, the provided techniques are useful for a variety of targets, particularly those comprising CD38.

[0219] In some embodiments, the target is damaged or defective tissue. In some embodiments, the target is damaged tissue. In some embodiments, the target is defective tissue. In some embodiments, the target is associated with a disease, disorder, or condition (e.g., cancer, wound, etc.). In some embodiments, the target is a tumor. In some embodiments, the target is or comprises a diseased cell. In some embodiments, the target is or comprises a cancer cell. In some embodiments, the target is a foreign body. In some embodiments, the target is or comprises an infectious agent. In some embodiments, the target is a microorganism. In some embodiments, the target is or comprises a bacterium. In some embodiments, the target is or comprises a virus. In some embodiments, the target comprises or expresses CD38.

[0220] In many embodiments, the target is a tissue and / or cell associated with a disease, disorder, or condition, particularly various types of cancer. In some embodiments, the target is or includes a cell associated with a condition, disorder, or disease. In some embodiments, the target is or includes a cell associated with cancer. In some embodiments, the cell includes or expresses CD38. Among other things, the present disclosure provides particularly useful techniques for selectively targeting cancer cells that include or express CD38 by the immune system via immune cells, for example, by the use of recruited antibodies (e.g., endogenous antibodies) and ARMs.

[0221] The targeting moiety typically includes one or more physical, chemical, and / or biological markers (e.g., CD38) that can be utilized, for example, by the target-binding moiety (e.g., ARM) of a provided compound to selectively recruit antibodies and / or fragments thereof and / or immune cells to the target.

[0222] In some embodiments, cells at the target site contain one or more characteristic agents useful for targeting (e.g., CD38). In some embodiments, such agents are proteins and / or fragments thereof. In some embodiments, such agents are antigens associated with a disease, disorder, or condition. In some embodiments, the target site and / or cells contain and / or express CD38 to which the target-binding moiety of a provided ARM can bind.

[0223] Linker part In some embodiments, the antibody-binding moiety is optionally connected to the target-binding moiety via a linker moiety. Various types of linker moieties and / or linker moieties for various purposes (e.g., those utilized in antibody-drug conjugates) can be utilized in accordance with the present disclosure.

[0224] The linker moiety can be either bivalent or multivalent. In some embodiments, the linker moiety is bivalent. In some embodiments, the linker is multivalent and connects more than two moieties.

[0225] In some embodiments, the linker moiety is L. In some embodiments, L is a covalent bond or a divalent or multivalent optionally substituted linear or branched C 1-100 is a group comprising one or more aliphatic, aryl, heteroaliphatic having 1 to 20 heteroatoms, heteroaromatic having 1 to 20 heteroatoms, or any combination thereof, wherein one or more methylene units of the group are optionally and independently selected from the group C 1-6 Alkylene, C 1-6 Alkenylene, divalent C with 1 to 5 heteroatoms 1-6Heteroaliphatic group, -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')- , -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S- , -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P(S )(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid residue, or -[(-OC(R')2-C(R')2-) n ]-, where n is 1 to 20. In some embodiments, each amino acid residue is independently a residue of an amino acid having the structure of formula AI, or a salt thereof. In some embodiments, each amino acid residue is independently substituted with -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 It has the structure —CO— or a salt thereof.

[0226] In some embodiments, L is divalent. In some embodiments, L is C 1-100 Aliphatic and C with 1-50 heteroatoms 1-100 heteroaliphatic, divalent or optionally substituted, straight or branched chain group selected from the group, wherein one or more methylene units of the group are optionally and independently selected from C 1-6 Alkylene, C 1-6 Alkenylene, divalent C with 1 to 5 heteroatoms 1-6Heteroaliphatic group, -C≡C-, -Cy-, -C(R')2-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')- , -C(O)C(R')2N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S -, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P (S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, amino acid, or -[(-OC(R')2-C(R')2-) n ]- is replaced by

[0227] In some embodiments, L is a covalent bond. In some embodiments, L is an optionally substituted straight or branched C 1-100 In some embodiments, L is an optionally substituted linear or branched C 6-100 In some embodiments, L is a divalent optionally substituted linear or branched C alkyl group having 1 to 20 heteroatoms, wherein one or more methylene units of the group are optionally and independently substituted. 5-100 In some embodiments, L is an optionally substituted linear or branched C alkyl group having 1 to 20 heteroatoms, wherein one or more methylene units of the group are optionally and independently substituted. 1-100 It is a heteroaliphatic group, in which one or more methylene units of the group are optionally and independently substituted.

[0228] In some embodiments, the linker moiety (e.g., L) is or comprises one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) polyethylene glycol units. In some embodiments, the linker moiety is -(CR2CR2O) n -, and each of R and n is independently as described in this disclosure. In some embodiments, the linker moiety is -(CH2CH2O) n -, and n is independently as described herein. In some embodiments, one or more methylene units of L is independently -(CH2CH2O) n In some embodiments, two or more methylene units of L are independently substituted with -(CR2CR2O) n -or-(CH2CH2O) n -. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, n is 11. In some embodiments, n is 12. In some embodiments, n is 13. In some embodiments, n is 14. In some embodiments, n is 15. In some embodiments, n is 16. In some embodiments, n is 17. In some embodiments, n is 18. In some embodiments, n is 19. In some embodiments, n is 20.

[0229] In some embodiments, the number of -(CR2CR2O)- units or -(CH2CHO)- units in a linker moiety, such as L, is at least about 1-20, 2-20, 3-30, 4-20, 5-20, 6-20, 7-20, 8-20, 9-20, 10-20, 11-20, 12-20, 13-20, 14-20, 15-20, or about or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. In some embodiments, it is about or at least about 1. In some embodiments, it is about or at least about 2. In some embodiments, it is about or at least about 3. In some embodiments, it is about or at least about 4. In some embodiments, it is about or at least about 5. In some embodiments, it is about or at least about 6. In some embodiments, it is about or at least about 7. In some embodiments, it is about or at least about 8. In some embodiments, it is about or at least about 9. In some embodiments, it is about or at least about 10. In some embodiments, it is about or at least about 11. In some embodiments, it is about or at least about 12. In some embodiments, it is about or at least about 13. In some embodiments, it is about or at least about 14. In some embodiments, it is about or at least about 15. In some embodiments, it is about or at least about 16. In some embodiments, it is about or at least about 17. In some embodiments, it is about or at least about 18. In some embodiments, it is about or at least about 19. In some embodiments, it is about or at least about 20.

[0230] In some embodiments, the linker moiety (e.g., L) can be one or more -(CR2CR2O) groups described herein. n -and / or-(CH2CH2O) n -, as well as one or more amino acid residues.

[0231] In some embodiments, the linker moiety (i.e., L) is [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] In some embodiments, the linker moiety (i.e., L) is or comprises: [ka] is or contains

[0232] In some embodiments, the linker moiety (e.g., L) is or includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more) amino acid residues. As used in this disclosure, "one or more" can be 1 to 100, 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or more. In some embodiments, one or more methylene units of L are independently replaced with an amino acid residue. In some embodiments, one or more methylene units of L are independently replaced with an amino acid residue, wherein the amino acid residue is a residue of an amino acid of Formula AI or a salt thereof. In some embodiments, one or more methylene units of L are independently replaced with an amino acid residue, each amino acid residue being independently selected from the group consisting of -N(R a1 )-L a1 -C(R a2 )(R a3 )-L a2 In some embodiments, the amino acid has the structure -CO- or a salt form thereof. In some embodiments, the amino acid is a natural amino acid. In some embodiments, the amino acid is glycine. In some embodiments, the amino acid is an unnatural amino acid. In some embodiments, the amino acid is a D-amino acid. In some embodiments, the amino acid is β-alanine. In some embodiments, the amino acid residue has the structure -C(O)-(CHCHO)-CHCHNR'- or a salt form thereof, where n is 0-20 (e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20), and R' is as described herein. In some embodiments, n is 0. In some embodiments, n is 0-12. In some embodiments, n is 1-12. In some embodiments, R' is -H.

[0233] In some embodiments, a linker moiety comprises one or more moieties (e.g., amino, carbonyl, etc.) that can be utilized to connect to other moieties. In some embodiments, a linker moiety comprises one or more -NR'-, where R' is as described in this disclosure. In some embodiments, -NR'- improves solubility. In some embodiments, -NR'- serves as a connection point to another moiety. In some embodiments, R' is -H. In some embodiments, one or more methylene units of L are independently replaced with -NR'-, where R' is as described in this disclosure.

[0234] In some embodiments, a linker moiety (e.g., L) comprises a -C(O)- group that can be used to connect moieties. In some embodiments, one or more methylene units of L are independently replaced with -C(O)-.

[0235] In some embodiments, a linker moiety (e.g., L) comprises an -NR'- group that can be utilized to connect moieties, in some embodiments, one or more methylene units of L are independently replaced with -N(R')-.

[0236] In some embodiments, a linker moiety (e.g., L) comprises a -C(O)NR'- group and can be used to connect moieties. In some embodiments, one or more methylene units of L are independently replaced with -C(O)N(R')-.

[0237] In some embodiments, a linker moiety (e.g., L) comprises a -C(R')2- group. In some embodiments, one or more methylene units of L are independently replaced with -C(R')2-. In some embodiments, -C(R')2- is -CHR'-. In some embodiments, R' is -(CH2)2C(O)NH(CH2) 11 In some embodiments, R' is -COOH. In some embodiments, R' is -(CH2)2COOH. In some embodiments, R' is -COOH.

[0238] In some embodiments, the linker moiety is or includes one or more ring moieties, e.g., one or more methylene units of L are replaced with -Cy-. In some embodiments, the linker moiety (e.g., L) includes an aryl ring. In some embodiments, the linker moiety (e.g., L) includes a heteroaryl ring. In some embodiments, the linker moiety (e.g., L) includes an aliphatic ring. In some embodiments, the linker moiety (e.g., L) includes a heterocyclyl ring. In some embodiments, the linker moiety (e.g., L) includes a polycyclic ring. In some embodiments, the ring of the linker moiety (e.g., L) has 3 to 20 members. In some embodiments, the ring is 5 members. In some embodiments, the ring is 6 members. In some embodiments, the ring of the linker is the product of a cycloaddition reaction (e.g., click chemistry, and variants thereof) utilized to link different moieties together.

[0239] In some embodiments, the linker moiety (e.g., L) is [ka] In some embodiments, the methylene units of L are or include: [ka] In some embodiments, -Cy- is substituted with [ka] is.

[0240] In some embodiments, a linker moiety (e.g., L) is or includes -Cy-. In some embodiments, a methylene unit of L is replaced with -Cy-. In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] is.

[0241] In some embodiments, the linker moiety (e.g., L) of a provided agent (e.g., a compound of Table 1) is: [ka] In some embodiments, [ka] is the structure of [ka] In some embodiments, [ka] In some embodiments, [ka] is.

[0242] In some embodiments, the linker moiety is as described in Table 1. Additional linker moieties include, for example, L 2 In some embodiments, L is any of the L groups described in this disclosure. 1 In some embodiments, L is any of the L groups described in this disclosure. 2 In some embodiments, L is any of the L groups described in this disclosure. 3 In some embodiments, L is any of the L groups described in this disclosure. b is.

[0243] In some embodiments, L is [ka] is.

[0244] In some embodiments, the linker comprises an amino acid sequence comprising one or more amino acid residues. [ka] In some embodiments, the linker is or comprises: [ka] In some embodiments, the linker is or comprises a Gly residue. In some embodiments, the linker is or comprises -(Gly)n-, where n is as described herein. In some embodiments, n is 1 to 10, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the linker is or comprises -Gly-Gly-. In some embodiments, the linker is or comprises -Gly-Gly-Gly-Gly-Gly-. Without intending to be limited by theory, in some embodiments, linkers comprising amino acid residues may provide rigidity and / or orientation of various moieties, which can facilitate, promote, and / or enhance one or more properties and / or activities.

[0245] In some embodiments, the linker is attached to the moiety (e.g., the target-binding moiety or the antibody-binding moiety) through the N-terminal residue (e.g., through an amino group) or through the C-terminal amino acid residue (e.g., through a -COOH group). In some embodiments, the linker is attached to the moiety through a side chain.

[0246] In some embodiments, the linker (e.g., L) is a divalent optionally substituted C 1-20 In some embodiments, the linker (e.g., L) is or comprises a divalent optionally substituted C 1-20In some embodiments, the divalent group is or comprises a linear alkylene group. In some embodiments, the divalent group is linear. In some embodiments, the linker (e.g., L) is a linear -(CH) n -, where n is 1 to 20 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20). In some embodiments, the linker (e.g., L) is NHR'-(CH2). n In some embodiments, the linker (e.g., L) is a residue of an amino acid having the structure -COOH or a salt thereof. n In some embodiments, R' is or comprises -CO- or a salt form thereof. In some embodiments, R' is -H. In some embodiments, the linker comprises an albumin binding moiety, as demonstrated herein.

[0247] In some embodiments, as used herein (e.g., in various moieties), n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10. In some embodiments, n is 11. In some embodiments, n is 12. In some embodiments, n is 13. In some embodiments, n is 14. In some embodiments, n is 15. In some embodiments, n is 16. In some embodiments, n is 17. In some embodiments, n is 18. In some embodiments, n is 19. In some embodiments, n is 20.

[0248] In some embodiments, the linker is or includes the portion between two cyclic peptide moieties of the compounds provided, for example, in Table 1, or a fragment thereof.

[0249] Specific Embodiments of Variables By way of example, exemplary embodiments of variables are described throughout this disclosure. As will be appreciated by those skilled in the art, embodiments for different variables may optionally be combined.

[0250] As defined above and described herein, ABT is an antibody binding moiety described herein. In some embodiments, ABT is an ABT of a compound selected from those shown in Table 1 below. In some embodiments, ABT is a moiety selected from Table A-1. In some embodiments, ABT is a moiety described in Table 1.

[0251] In some embodiments, L is a bivalent or polyvalent linker moiety that links one or more antibody binding moieties to one or more target binding moieties. In some embodiments, L is a bivalent linker moiety that connects ABT and TBT. In some embodiments, L is a polyvalent linker moiety that connects ABT and TBT.

[0252] In some embodiments, L is a linker moiety of a compound selected from those shown in Table 1 below.

[0253] As defined above and described herein, TBT is a target binding moiety described herein.

[0254] In some embodiments, TBT is a target binding moiety of a compound selected from those shown in Table 1 below. In some embodiments, TBT is a moiety selected from Table T-1. In some embodiments, TBT is a moiety described in Table 1.

[0255] R, as defined above and described herein 1 , R 3 , and R 5 each independently is hydrogen or C 1-6an optionally substituted group selected from an aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocycle, a phenyl, an 8-10 membered bicyclic aromatic carbocycle, a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or R 1 and R 1’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered saturated or partially unsaturated spirocyclic carbocycle or a 4- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 3 and R 3’ optionally, together with their intervening carbon atoms, form a 3- to 8-membered saturated or partially unsaturated spirocyclic carbocycle or a 4- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and R bonded to the same carbon atom 5 Groups and R 5’ Groups optionally, taken together with their intervening carbon atoms, form a 3-8 membered saturated or partially unsaturated spirocyclic carbocycle or a 4-8 membered saturated or partially unsaturated spirocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two R 5 The groups, optionally together with their intervening atoms, are C 1-10 forming a divalent linear or branched saturated or unsaturated hydrocarbon chain in which 1 to 3 methylene units are independently and optionally -S-, -SS-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, or -Cy 1 -, and each -Cy 1- is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0256] In some embodiments, R 1 is hydrogen. In some embodiments, R 1 is C 1-6 R is an optionally substituted group selected from aliphatic, 3-8 membered saturated or partially unsaturated monocyclic carbocycle, phenyl, 8-10 membered bicyclic aromatic carbocycle, 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 1 is an optionally substituted C 1-6 In some embodiments, R 1 is an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring. In some embodiments, R 1 is optionally substituted phenyl. In some embodiments, R 1 is an optionally substituted 8-10 membered bicyclic aromatic carbocycle. In some embodiments, R 1 is an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 1 is an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 1 is an optionally substituted 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0257] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] is.

[0258] In some embodiments, R1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] is.

[0259] In some embodiments, R 1 teeth, [ka] In some embodiments, R 1 teeth, [ka] is.

[0260] In some embodiments, R 1 and R 1’ optionally, taken together with their intervening carbon atoms, form a 3-8 membered saturated or partially unsaturated spirocyclic carbocyclic ring. In some embodiments, R 1 and R 1’ optionally, together with their intervening carbon atoms, form a 4-8 membered saturated or partially unsaturated spirocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0261] In some embodiments, R 1 is selected from those shown in Table 1 below.

[0262] In some embodiments, R is an R group described in this disclosure. 1 In some embodiments, R a2 is the R described in this disclosure 1 In some embodiments, R a3 is the R described in this disclosure 1 is.

[0263] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 is C 1-6 R is an optionally substituted group selected from aliphatic, 3-8 membered saturated or partially unsaturated monocyclic carbocycle, phenyl, 8-10 membered bicyclic aromatic carbocycle, 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 3 is an optionally substituted C 1-6 In some embodiments, R 3is an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring. In some embodiments, R 3 is optionally substituted phenyl. In some embodiments, R 3 is an optionally substituted 8-10 membered bicyclic aromatic carbocycle. In some embodiments, R 3 is an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R 3 is an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 3 is an optionally substituted 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0264] In some embodiments, R 3 is methyl. In some embodiments, R 3 teeth, [ka] In some embodiments, R 3 teeth, [ka] is.

[0265] In some embodiments, R 3 teeth, [ka] In some embodiments, R 3 teeth, [ka] In some embodiments, R 3 teeth, [ka] and the binding site has the (S) stereochemistry. In some embodiments, R 3 teeth, [ka] and the binding site has the (R) stereochemistry. In some embodiments, R 3 teeth, [ka] and the binding site has the (S) stereochemistry. In some embodiments, R 3 teeth, [ka] and the binding site has the (R) stereochemistry.

[0266] In some embodiments, R 3 teeth, [ka] and the binding site has the (S) stereochemistry. In some embodiments, R 3 teeth, [ka] and the binding site has the (R) stereochemistry.

[0267] In some embodiments, R 3 and R 3’ optionally, taken together with their intervening carbon atoms, form a 3-8 membered saturated or partially unsaturated spirocyclic carbocyclic ring. In some embodiments, R 3 and R 3’ optionally, together with their intervening carbon atoms, form a 4-8 membered saturated or partially unsaturated spirocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0268] In some embodiments, R 3is selected from those shown in Table 1 below.

[0269] In some embodiments, R is an R group described in this disclosure. 2 In some embodiments, R a2 is the R described in this disclosure 2 In some embodiments, R a3 is the R described in this disclosure 2 is.

[0270] In some embodiments, R 5 is hydrogen. In some embodiments, R 5 is C 1-6 R is an optionally substituted group selected from aliphatic, 3-8 membered saturated or partially unsaturated monocyclic carbocycle, phenyl, 8-10 membered bicyclic aromatic carbocycle, 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 5 is an optionally substituted C 1-6 In some embodiments, R 5 is an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring. In some embodiments, R 5 is optionally substituted phenyl. In some embodiments, R 5 is an optionally substituted 8-10 membered bicyclic aromatic carbocycle. In some embodiments, R 5 is an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R 5 is an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 5is an optionally substituted 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0271] In some embodiments, R 5 is methyl. In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] and the binding site has the (S) stereochemistry. In some embodiments, R 5 teeth, [ka] and the binding site has the (R) stereochemistry. In some embodiments, R 5 teeth, [ka] and the binding site has the (S) stereochemistry. In some embodiments, R 5 teeth, [ka] and the binding site has the (R) stereochemistry. In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] is.

[0272] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] is.

[0273] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] is.

[0274] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R5 teeth, [ka] is.

[0275] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 4 is 5 [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 5 teeth, [ka] In some embodiments, R 4 teeth, [ka] and the binding site has the (S) stereochemistry. In some embodiments, R 4 teeth, [ka] and the binding site has the (R) stereochemistry.

[0276] In some embodiments, R 5 and R 5’ optionally, taken together with their intervening carbon atoms, form a 3-8 membered saturated or partially unsaturated spirocyclic carbocyclic ring. In some embodiments, R 5 and R 5’ optionally, together with their intervening carbon atoms, form a 4-8 membered saturated or partially unsaturated spirocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0277] In some embodiments, two R 5 The groups, together with their intervening atoms, form C 1-10 wherein 1 to 3 methylene units of the chain are independently and optionally -S-, -SS-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, or -Cy 1 -, and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0278] In some embodiments, two R 5 The groups, together with their intervening atoms, [ka] In some embodiments, two R 5 The groups, together with their intervening atoms, [ka] In some embodiments, two R 5 The groups, together with their intervening atoms, [ka] In some embodiments, two R 5 The groups, together with their intervening atoms, [ka] Form.

[0279] In some embodiments, R 5 is selected from those shown in Table 1 below.

[0280] In some embodiments, R is an R group described in this disclosure. 5 In some embodiments, R a2 is the R described in this disclosure 5 In some embodiments, R a3 is the R described in this disclosure 5 is.

[0281] R, as defined above and described herein 1’ , R 3’ , and R 5’ each independently represents hydrogen or C 1-3 It is aliphatic.

[0282] In some embodiments, R 1’ is hydrogen. In some embodiments, R 1’ is C1-3 It is aliphatic.

[0283] In some embodiments, R 1’ is methyl. In some embodiments, R 1’ is ethyl. In some embodiments, R 1’ is n-propyl. In some embodiments, R 1’ is isopropyl. In some embodiments, R 1’ is cyclopropyl.

[0284] In some embodiments, R 1’ is selected from those shown in Table 1 below.

[0285] In some embodiments, R 3’ is hydrogen. In some embodiments, R 3’ is C 1-3 It is aliphatic.

[0286] In some embodiments, R 3’ is methyl. In some embodiments, R 3’ is ethyl. In some embodiments, R 3’ is n-propyl. In some embodiments, R 3’ is isopropyl. In some embodiments, R 3’ is cyclopropyl.

[0287] In some embodiments, R 3’ is selected from those shown in Table 1 below.

[0288] In some embodiments, R 5’ is hydrogen. In some embodiments, R 5’ is C 1-3 It is aliphatic.

[0289] In some embodiments, R 5’ is methyl. In some embodiments, R 5’ is ethyl. In some embodiments, R 5’is n-propyl. In some embodiments, R 5’ is isopropyl. In some embodiments, R 5’ is cyclopropyl.

[0290] In some embodiments, R 5’ is selected from those shown in Table 1 below.

[0291] R, as defined above and described herein 2 , R 4 , and R 6 each independently represents hydrogen or C 1-4 Aliphatic or R 2 and R 1 optionally, together with their intervening atoms, form a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 4 and R 3 optionally, together with their intervening atoms, form a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or R 6 group and its adjacent R 5 The groups optionally, together with their intervening atoms, form a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0292] In some embodiments, R 2 is hydrogen. In some embodiments, R 2 is C 1-4 In some embodiments, R 2 is methyl. In some embodiments, R 2 is ethyl. In some embodiments, R 2 is n-propyl. In some embodiments, R 2 is isopropyl. In some embodiments, R 2 is n-butyl. In some embodiments, R2 is isobutyl. In some embodiments, R 2 is tert-butyl.

[0293] In some embodiments, R 2 and R 1 together with their intervening atoms form a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0294] In some embodiments, R 2 and R 1 together with their intervening atoms, [ka] In some embodiments, R 2 and R 1 together with their intervening atoms, [ka] Form.

[0295] In some embodiments, R 2 is selected from those shown in Table 1 below.

[0296] In some embodiments, R 4 is hydrogen. In some embodiments, R 4 is C 1-4 In some embodiments, R 4 is methyl. In some embodiments, R 4 is ethyl. In some embodiments, R 4 is n-propyl. In some embodiments, R 4 is isopropyl. In some embodiments, R 4 is n-butyl. In some embodiments, R 4 is isobutyl. In some embodiments, R 4 is tert-butyl.

[0297] In some embodiments, R 4 and R 3 together with their intervening atoms form a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0298] In some embodiments, R 4 and R 3 together with their intervening atoms, [ka] In some embodiments, R 4 and R 3 together with their intervening atoms, [ka] Form.

[0299] In some embodiments, R 4 is selected from those shown in Table 1 below.

[0300] In some embodiments, R 6 is hydrogen. In some embodiments, R 6 is C 1-4 In some embodiments, R 6 is methyl. In some embodiments, R 6 is ethyl. In some embodiments, R 6 is n-propyl. In some embodiments, R 6 is isopropyl. In some embodiments, R 6 is n-butyl. In some embodiments, R 6 is isobutyl. In some embodiments, R 6 is tert-butyl.

[0301] In some embodiments, R 6 group and its adjacent R 5The groups, taken together with their intervening atoms, form a 4- to 8-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0302] In some embodiments, R 6 group and its adjacent R 5 The groups, together with their intervening atoms, [ka] In some embodiments, R 6 group and its adjacent R 5 The groups, together with their intervening atoms, [ka] Form.

[0303] In some embodiments, R 6 is selected from those shown in Table 1 below.

[0304] In some embodiments, R is an R group described in this disclosure. 1’ In some embodiments, R a2 is the R described in this disclosure 1’ In some embodiments, R a3 is the R described in this disclosure 1’ In some embodiments, R is an R group described in this disclosure. 3’ In some embodiments, R a2 is the R described in this disclosure 3’ In some embodiments, R a3 is the R described in this disclosure 3’ In some embodiments, R is an R group described in this disclosure. 2 In some embodiments, R a2 is the R described in this disclosure 2 In some embodiments, R a3 is the R described in this disclosure 2 In some embodiments, R is an R group as described herein. 4In some embodiments, R a2 is the R described in this disclosure 4 In some embodiments, R a3 is the R described in this disclosure 4 In some embodiments, R is an R group described in this disclosure. 6 In some embodiments, R a2 is the R described in this disclosure 6 In some embodiments, R a3 is the R described in this disclosure 6 is.

[0305] As defined above and described herein, L 1 teeth, [ka] is a trivalent linker moiety connecting

[0306] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] is.

[0307] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] In some embodiments, L 1 teeth, [ka] is.

[0308] In some embodiments, L 1 is selected from those shown in Table 1 below.

[0309] As defined above and described herein, L 2 is a covalent bond or C 1-10 wherein 1 to 3 methylene units of the chain are independently and optionally selected from -S-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, [ka] or -Cy 1 -, and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0310] In some embodiments, L 2 is a covalent bond. In some embodiments, L 2 is C 1-10 wherein 1 to 3 methylene units of the chain are independently and optionally selected from -S-, -N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -C(O)N(R)-, -N(R)C(O)-, -S(O)-, -S(O)2-, [ka] or -Cy 1 -, and each -Cy 1 - is independently a 5-6 membered heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0311] In some embodiments, L 2 teeth, [ka] In some embodiments, L 2 teeth, [ka] In some embodiments, L 2 teeth, [ka] In some embodiments, L 2 teeth, [ka] In some embodiments, L 2 teeth, [ka] In some embodiments, L 2 teeth, [ka] is.

[0312] In some embodiments, L 2 is selected from those shown in Table 1 below.

[0313] In some embodiments, L is any of the L groups described in this disclosure. 2 is.

[0314] As defined above and described herein, TBT is a target binding moiety.

[0315] In some embodiments, TBT is the target binding moiety.

[0316] In some embodiments, TBT is [ka] In some embodiments, TBT is: [ka] is.

[0317] In some embodiments, the TBT is selected from those shown in Table 1 below.

[0318] As defined above and described herein, each of m and n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0319] In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4. In some embodiments, m is 5. In some embodiments, m is 6. In some embodiments, m is 7. In some embodiments, m is 8. In some embodiments, m is 9. In some embodiments, m is 10.

[0320] In some embodiments, m is selected from those shown in Table 1 below.

[0321] In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4. In some embodiments, n is 5. In some embodiments, n is 6. In some embodiments, n is 7. In some embodiments, n is 8. In some embodiments, n is 9. In some embodiments, n is 10.

[0322] In some embodiments, n is selected from those shown in Table 1 below.

[0323] R, as defined above and described herein 7 each independently is hydrogen or C 1-6 an optionally substituted group selected from aliphatic, 3-8 membered saturated or partially unsaturated monocyclic carbocycle, phenyl, 8-10 membered bicyclic aromatic carbocycle, 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or R 7 Groups and R 7’Groups optionally, together with their intervening carbon atoms, form a 3- to 8-membered saturated or partially unsaturated spirocyclic carbocycle or a 4- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0324] In some embodiments, R 7 is hydrogen. In some embodiments, R 7 is C 1-6 R is an optionally substituted group selected from aliphatic, 3-8 membered saturated or partially unsaturated monocyclic carbocycle, phenyl, 8-10 membered bicyclic aromatic carbocycle, 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 7 is an optionally substituted C 1-6 In some embodiments, R 7 is an optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring. In some embodiments, R 7 is optionally substituted phenyl. In some embodiments, R 7 is an optionally substituted 8-10 membered bicyclic aromatic carbocycle. In some embodiments, R 7 is an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R 7 is an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 7 is an optionally substituted 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0325] In some embodiments, R 7 is methyl. In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] is.

[0326] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] is.

[0327] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] is.

[0328] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] In some embodiments, R 7 teeth, [ka] is.

[0329] In some embodiments, R 7 Groups and R 7’ The R groups, taken together with their intervening carbon atoms, form a 3- to 8-membered saturated or partially unsaturated spirocyclic carbocyclic ring. In some embodiments, R 7 Groups and R 7’ The groups, together with their intervening carbon atoms, form a 4- to 8-membered saturated or partially unsaturated spirocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0330] In some embodiments, R 7 is selected from those shown in Table 1 below.

[0331] R, as defined above and described herein 7’ each independently represents hydrogen or C 1-3 It is aliphatic.

[0332] In some embodiments, R 7’ is hydrogen. In some embodiments, R 7’ is methyl. In some embodiments, R 7’ is ethyl. In some embodiments, R 7’ is n-propyl. In some embodiments, R 7’ is isopropyl.

[0333] In some embodiments, R 7’ is selected from those shown in Table 1 below.

[0334] R, as defined above and described herein 8each independently represents hydrogen or C 1-4 Aliphatic or R 8 group and its adjacent R 7 The groups optionally, together with their intervening atoms, form a 4-8 membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0335] In some embodiments, R 8 is hydrogen. In some embodiments, R 8 is C 1-4 In some embodiments, R 8 is methyl. In some embodiments, R 8 is ethyl. In some embodiments, R 8 is n-propyl. In some embodiments, R 8 is isopropyl. In some embodiments, R 8 is n-butyl. In some embodiments, R 8 is isobutyl. In some embodiments, R 8 is tert-butyl.

[0336] In some embodiments, R 8 group and its adjacent R 7 The groups, taken together with their intervening atoms, form a 4- to 8-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0337] In some embodiments, R 8 group and its adjacent R 7 The groups, together with their intervening atoms, [ka] In some embodiments, R 8 group and its adjacent R 7 The groups, together with their intervening atoms, [ka] Form.

[0338] In some embodiments, R 8 is selected from those shown in Table 1 below.

[0339] R, as defined above and described herein 9 is hydrogen, C 1-3 Aliphatic, or -C(O)C 1-3 It is aliphatic.

[0340] In some embodiments, R 9 is hydrogen. In some embodiments, R 9 is C 1-3 In some embodiments, R 9 is -C(O)C 1-3 It is aliphatic.

[0341] In some embodiments, R 9 is methyl. In some embodiments, R 9 is ethyl. In some embodiments, R 9 is n-propyl. In some embodiments, R 9 is isopropyl. In some embodiments, R 9 is cyclopropyl.

[0342] In some embodiments, R 9 is —C(O)Me. In some embodiments, R 9 is —C(O)Et. In some embodiments, R 9 is —C(O)CH CH CH. In some embodiments, R 9 is —C(O)CH(CH). In some embodiments, R 9 is —C(O)cyclopropyl.

[0343] In some embodiments, R 9 is selected from those shown in Table 1 below.

[0344] In some embodiments, R is an R group described in this disclosure. 7 In some embodiments, R a2 is the R described in this disclosure 7 In some embodiments, R a3 is the R described in this disclosure 7 In some embodiments, R is an R group described in this disclosure. 7’ In some embodiments, R a2 is the R described in this disclosure 7’ In some embodiments, R a3 is the R described in this disclosure 7’ In some embodiments, R is an R group described in this disclosure. 8 In some embodiments, R a2 is the R described in this disclosure 8 In some embodiments, R a3 is the R described in this disclosure 8 In some embodiments, R is an R group described in this disclosure. 8’ In some embodiments, R a2 is the R described in this disclosure 8’ In some embodiments, R a3 is the R described in this disclosure 8’ In some embodiments, R is an R group described in this disclosure. 9 In some embodiments, R a2 is the R described in this disclosure 9 In some embodiments, R a3 is the R described in this disclosure 9 is.

[0345] As defined above and described herein, L 3 TBT and [ka] is a bivalent linker moiety connecting

[0346] In some embodiments, L 3 TBT and [ka] is a bivalent linker moiety connecting

[0347] In some embodiments, L 3 teeth, [ka] In some embodiments, L 3 teeth, [ka] In some embodiments, L 3 teeth, [ka] In some embodiments, L 3 teeth, [ka] In some embodiments, L 3 teeth, [ka] In some embodiments, L 3 teeth, [ka] is.

[0348] In some embodiments, L 3 is selected from those shown in Table 1 below.

[0349] In some embodiments, L is any of the L groups described in this disclosure. 3 is.

[0350] As defined above and described herein, o is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0351] In some embodiments, o is 1. In some embodiments, o is 2. In some embodiments, o is 3. In some embodiments, o is 4. In some embodiments, o is 5. In some embodiments, o is 6. In some embodiments, o is 7. In some embodiments, o is 8. In some embodiments, o is 9. In some embodiments, o is 10.

[0352] In some embodiments, o is selected from those shown in Table 1 below.

[0353] In certain embodiments, the present disclosure provides compounds of formula II, wherein L 2 teeth, [ka] and TBT is [ka] whereby the compound of formula II-a: [ka] or a pharmaceutically acceptable salt thereof, wherein L 1 , R 1 , R 1’ , R 2 , R 3 , R 3’ , R 4 , R 5 , R 5’ , R 6 Each of, and m, both alone and in combination, is as defined above and described in the embodiments herein.

[0354] In certain embodiments, the present disclosure provides compounds of formula II, wherein L 2 teeth, [ka] and TBT is [ka] and thereby producing a compound of formula II-b: [ka] or a pharmaceutically acceptable salt thereof, wherein L 1 , R 1 , R 1’ , R 2 , R 3 , R 3’ , R 4 , R 5 , R 5’ , R 6 Each of, and m, both alone and in combination, is as defined above and described in the embodiments herein.

[0355] In certain embodiments, the present disclosure provides compounds of formula II, wherein L 2 teeth, [ka] and TBT is [ka] and thereby producing a compound of formula II-c: [ka] or a pharmaceutically acceptable salt thereof, wherein L 1 , R 1 , R 1’ , R 2 , R 3 , R 3’ , R 4 , R 5 , R 5’ , R 6 Each of, and m, both alone and in combination, is as defined above and described in the embodiments herein.

[0356] In certain embodiments, the present disclosure provides compounds of formula II, wherein L 2 teeth, [ka] and TBT is [ka] and thereby providing a compound of formula II-d: [ka] or a pharmaceutically acceptable salt thereof, wherein L 1 , R 1 , R 1’ , R 2 , R 3 , R 3’ , R 4 , R 5 , R 5’ , R 6 Each of, and m, both alone and in combination, is as defined above and described in the embodiments herein.

[0357] In certain embodiments, the present disclosure provides compounds of formula II, wherein L 2 teeth, [ka] and TBT is [ka] whereby a compound of formula II-e: [ka] or a pharmaceutically acceptable salt thereof, wherein L 1 , R 1 , R 1’ , R 2 , R 3 , R 3’ , R 4 , R 5 , R 5’ , R 6 Each of, and m, both alone and in combination, is as defined above and described in the embodiments herein.

[0358] In certain embodiments, the present disclosure provides compounds of formula II, wherein L 2 teeth, [ka] and TBT is [ka] and thereby providing a compound of formula II-f: [ka] or a pharmaceutically acceptable salt thereof, wherein L 1 , R 1 , R 1’ , R 2 , R 3 , R 3’ , R 4 , R 5 , R 5’ , R 6 Each of, and m, both alone and in combination, is as defined above and described in the embodiments herein.

[0359] In some embodiments, R a1 is R as described in this disclosure. In some embodiments, R a1 is an optionally substituted C 1-4 In some embodiments, R a1 is an optionally substituted C 1-4 In some embodiments, R a1 is methyl.

[0360] In some embodiments, L a1 is the L described in this disclosure a In some embodiments, L a1 is a covalent bond.

[0361] In some embodiments, L a2 is the L described in this disclosure a In some embodiments, L a2 is a covalent bond.

[0362] In some embodiments, L T is the L described herein a In some embodiments, L T is L as described herein. In some embodiments, L T is a covalent bond. In some embodiments, L T is —CH—C(O)—. In some embodiments, L T links the -S- of the side chain (e.g., via -CH2) to the amino group of the amino acid residue (e.g., via -C(O)-).

[0363] In some embodiments, L a is a covalent bond. In some embodiments, L a is C1-C 10 Aliphatic or C1-C with 1-5 heteroatoms 10 heteroaliphatic, wherein one or more methylene units of the group are optionally and independently replaced with -C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L a is an optionally substituted divalent group selected from C1-C5 aliphatic or C1-C5 heteroaliphatic having 1 to 5 heteroatoms, wherein one or more methylene units of the group are optionally and independently replaced with -C(R')2-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C2-, -S(O)2N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L ais an optionally substituted divalent C-C aliphatic group, wherein one or more methylene units of the group are optionally and independently replaced with -C(R')-, -Cy-, -O-, -S-, -SS-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O)N(R')-, -C(O)S-, or -C(O)O-. In some embodiments, L a is an optionally substituted divalent C1-C5 aliphatic. In some embodiments, L a is an optionally substituted divalent C1-C5 heteroaliphatic having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0364] In some embodiments, R a2 is R as described in this disclosure. In some embodiments, R a2 is the side chain of a natural amino acid. In some embodiments, R a3 is R as described in this disclosure. In some embodiments, R a3 is the side chain of a natural amino acid. In some embodiments, R 2a and R 3a In some embodiments, one of R a2 and / or R a3 is R, and R is optionally substituted C 1-8 In some embodiments, R is an optionally substituted linear C 2-8 In some embodiments, R is a straight chain C alkyl. 2-8 In some embodiments, R is an optionally substituted branched C alkyl. 2-8 In some embodiments, R is a branched C alkyl. 2-8 In some embodiments, R is alkyl. In some embodiments, R is n-pentyl. In some embodiments, R is substituted phenyl. In some embodiments, R is optionally substituted -CH-phenyl. In some embodiments, R is 4-phenylphenyl-CH-.

[0365] In some embodiments, each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently selected from the group consisting of C 3-20 Alicyclic ring, C 6-20 In some embodiments, each -Cy- is independently selected from C, an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. 3-20 Alicyclic ring, C 6-20 An optionally substituted divalent group selected from an aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, -Cy- is, for example, a substituted or unsubstituted heterocyclic group selected from R and Cy. L In the case of

[0047] , an optionally substituted ring as described in this disclosure is divalent.

[0366] In some embodiments, -Cy- is monocyclic. In some embodiments, -Cy- is bicyclic. In some embodiments, -Cy- is polycyclic. In some embodiments, -Cy- is saturated. In some embodiments, -Cy- is partially unsaturated. In some embodiments, -Cy- is aromatic. In some embodiments, -Cy- comprises a saturated monocyclic moiety. In some embodiments, -Cy- comprises a partially unsaturated monocyclic moiety. In some embodiments, -Cy- comprises an aromatic monocyclic moiety. In some embodiments, -Cy- comprises a combination of saturated, partially unsaturated, and / or aromatic cyclic moieties. In some embodiments, -Cy- is or comprises a 3-membered ring. In some embodiments, -Cy- is or comprises a 4-membered ring. In some embodiments, -Cy- is or comprises a 5-membered ring. In some embodiments, -Cy- is or comprises a 6-membered ring. In some embodiments, -Cy- is or comprises a 7-membered ring. In some embodiments, -Cy- is or comprises an 8-membered ring. In some embodiments, -Cy- is or comprises a 9-membered ring. In some embodiments, -Cy- is or comprises a 10-membered ring. In some embodiments, -Cy- is or comprises an 11-membered ring. In some embodiments, -Cy- is or comprises a 12-membered ring. In some embodiments, -Cy- is or comprises a 13-membered ring. In some embodiments, -Cy- is or comprises a 14-membered ring. In some embodiments, -Cy- is or comprises a 15-membered ring. In some embodiments, -Cy- is or comprises a 16-membered ring. In some embodiments, -Cy- is or comprises a 17-membered ring. In some embodiments, -Cy- is or comprises an 18-membered ring. In some embodiments, -Cy- is or comprises a 19-membered ring. In some embodiments, -Cy- is or comprises a 20-membered ring.

[0367] In some embodiments, -Cy- is an optionally substituted divalent C 3-20In some embodiments, -Cy- is or comprises an optionally substituted divalent saturated C 3-20 In some embodiments, -Cy- is or comprises an optionally substituted divalent partially unsaturated C 3-20 is or comprises an alicyclic ring. In some embodiments, for example, in alicyclic embodiments for R, -Cy-H is an optionally substituted alicyclic ring as described herein.

[0368] In some embodiments, -Cy- is an optionally substituted C 6-20 In some embodiments, -Cy- is or includes an optionally substituted phenylene. In some embodiments, -Cy- is or includes an optionally substituted 1,2-phenylene. In some embodiments, -Cy- is or includes an optionally substituted 1,3-phenylene. In some embodiments, -Cy- is or includes an optionally substituted 1,4-phenylene. In some embodiments, -Cy- is or includes an optionally substituted divalent naphthalene ring. In some embodiments, for example, in embodiments where R is aryl, -Cy-H is an optionally substituted aryl as described herein.

[0369] In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 20-membered heteroaryl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 20-membered heteroaryl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heteroaryl ring having 1 to 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heteroaryl ring having 1 to 2 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5-6 membered heteroaryl ring having one heteroatom independently selected from oxygen, nitrogen, and sulfur. In some embodiments, for example, in embodiments where R is heteroaryl, -Cy-H is an optionally substituted heteroaryl as described herein. In some embodiments, -Cy- is [ka] is.

[0370] In some embodiments, -Cy- is or includes an optionally substituted divalent 3- to 20-membered heterocyclyl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, -Cy- is or includes an optionally substituted divalent 3- to 20-membered heterocyclyl ring having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 3- to 6-membered heterocyclyl ring having 1 to 4 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heterocyclyl ring having 1 to 4 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heterocyclyl ring having 1 to 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heterocyclyl ring having 1 to 2 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent 5- to 6-membered heterocyclyl ring having 1 heteroatom independently selected from oxygen, nitrogen, and sulfur. In some embodiments, -Cy- is or includes an optionally substituted divalent saturated heterocyclyl group. In some embodiments, -Cy- is or includes an optionally substituted divalent partially unsaturated heterocyclyl group. In some embodiments, for example, in embodiments where R is heterocyclyl, -Cy-H is an optionally substituted heterocyclyl as described herein.

[0371] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] is.

[0372] In some embodiments, each Xaa is independently an amino acid residue. In some embodiments, each Xaa is independently an amino acid residue of an amino acid of formula AI.

[0373] In some embodiments, t is 0. In some embodiments, t is 1 to 50. In some embodiments, t is z as described in this disclosure.

[0374] In some embodiments, y is 1. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, y is 4. In some embodiments, y is 5. In some embodiments, y is 6. In some embodiments, y is 7. In some embodiments, y is 8. In some embodiments, y is 9. In some embodiments, y is 10. In some embodiments, y is 11. In some embodiments, y is 12. In some embodiments, y is 13. In some embodiments, y is 14. In some embodiments, y is 15. In some embodiments, y is 16. In some embodiments, y is 17. In some embodiments, y is 18. In some embodiments, y is 19. In some embodiments, y is 20. In some embodiments, y is greater than 20.

[0375] In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is 4. In some embodiments, z is 5. In some embodiments, z is 6. In some embodiments, z is 7. In some embodiments, z is 8. In some embodiments, z is 9. In some embodiments, z is 10. In some embodiments, z is 11. In some embodiments, z is 12. In some embodiments, z is 13. In some embodiments, z is 14. In some embodiments, z is 15. In some embodiments, z is 16. In some embodiments, z is 17. In some embodiments, z is 18. In some embodiments, z is 19. In some embodiments, z is 20. In some embodiments, z is greater than 20.

[0376] In some embodiments, R c is R' as described in this disclosure. In some embodiments, R c is R as described in this disclosure. In some embodiments, R c is —N(R′) 2 , where each R′ is independently as described in this disclosure. c is -NH. In some embodiments, R c is RC(O)—, where R is as described in this disclosure. In some embodiments, R c is -H.

[0377] In some embodiments, a is 1. In some embodiments, a is 2 to 100. In some embodiments, a is 5. In some embodiments, a is 10. In some embodiments, a is 20. In some embodiments, a is 50.

[0378] In some embodiments, b is 1. In some embodiments, b is 2 to 100. In some embodiments, b is 5. In some embodiments, b is 10. In some embodiments, b is 20. In some embodiments, b is 50.

[0379] In some embodiments, a1 is 0. In some embodiments, a1 is 1.

[0380] In some embodiments, a2 is 0. In some embodiments, a2 is 1.

[0381] In some embodiments, L b is the L described in this disclosure a In some embodiments, L b In some embodiments, L b In some embodiments, L b In some embodiments, L b In some embodiments, L b includes -C(O)-N(R')-.

[0382] In some embodiments, R' is -R, -C(O)R, -C(O)OR, or -S(O)R, where R is as described in this disclosure. In some embodiments, R' is R, where R is as described in this disclosure. In some embodiments, R' is -C(O)R, where R is as described in this disclosure. In some embodiments, R' is -C(O)OR, where R is as described in this disclosure. In some embodiments, R' is -S(O)R, where R is as described in this disclosure. In some embodiments, R' is hydrogen. In some embodiments, R' is not hydrogen. In some embodiments, R' is R, where R is an optionally substituted C group as described in this disclosure. 1-20 In some embodiments, R' is R, where R is an optionally substituted C as described herein. 1-20In some embodiments, R' is R, where R is an optionally substituted C as described herein. 6-20 In some embodiments, R' is R, where R is optionally substituted C as described herein. 6-20 In some embodiments, R' is R, where R is an optionally substituted C as described herein. 6-20 In some embodiments, R' is R and R is a 5-20 membered heteroaryl optionally substituted as described herein. In some embodiments, R' is R and R is a 3-20 membered heterocyclyl optionally substituted as described herein. In some embodiments, two or more R' are R, optionally and independently, joined together to form a ring optionally substituted as described herein.

[0383] In some embodiments, each R is independently —H or —C 1-30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently, taken together with that atom, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0384] In some embodiments, each R is independently —H or —C 1-30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-30 an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or Two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0385] In some embodiments, each R is independently —H or —C 1-20 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-20 Heteroaliphatic, C 6-20 Aryl, C 6-20 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-20 an optionally substituted group selected from arylheteroaliphatic, 5-20 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-20 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon; or two R groups, optionally and independently, together form a covalent bond; or Two or more R groups on the same atom optionally and independently combine with that atom to form an optionally substituted 3-20 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. Two or more R groups on two or more atoms optionally and independently, taken together with their intervening atoms, form an optionally substituted 3- to 20-membered monocyclic, bicyclic, or polycyclic ring having, in addition to their intervening atoms, 0-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0386] In some embodiments, each R is independently —H or C 1-30Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30 Aryl, C 6-30 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-30 arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-30 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0387] In some embodiments, each R is independently —H or C 1-20 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-20 Heteroaliphatic, C 6-20 Aryl, C 6-20 Arylaliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 6-20 arylheteroaliphatic, 5-20 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and 3-20 membered heterocyclyl having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0388] In some embodiments, R is hydrogen. In some embodiments, R is not hydrogen. In some embodiments, R is C 1-30 Aliphatic, C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon 1-30 Heteroaliphatic, C 6-30An optionally substituted group selected from aryl, a 5-30 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon, and a 3-30 membered heterocycle having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon.

[0389] In some embodiments, R is hydrogen or C 1-20 an optionally substituted group selected from aliphatic, phenyl, a 3- to 7-membered saturated or partially unsaturated carbocycle, an 8- to 10-membered saturated or partially unsaturated bicyclic aryl ring, a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 4- to 7-membered saturated or partially unsaturated heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 7- to 10-membered saturated or partially unsaturated bicyclic heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0390] In some embodiments, R is optionally substituted C 1-30 In some embodiments, R is an optionally substituted C 1-20 In some embodiments, R is an optionally substituted C 1-15 In some embodiments, R is an optionally substituted C 1-10 In some embodiments, R is an optionally substituted C 1-6 In some embodiments, R is an optionally substituted C 1-6In some embodiments, R is alkyl. In some embodiments, R is optionally substituted hexyl, pentyl, butyl, propyl, ethyl, or methyl. In some embodiments, R is optionally substituted hexyl. In some embodiments, R is optionally substituted pentyl. In some embodiments, R is optionally substituted butyl. In some embodiments, R is optionally substituted propyl. In some embodiments, R is optionally substituted ethyl. In some embodiments, R is optionally substituted methyl. In some embodiments, R is hexyl. In some embodiments, R is pentyl. In some embodiments, R is butyl. In some embodiments, R is propyl. In some embodiments, R is ethyl. In some embodiments, R is methyl. In some embodiments, R is isopropyl. In some embodiments, R is n-propyl. In some embodiments, R is tert-butyl. In some embodiments, R is sec-butyl. In some embodiments, R is n-butyl. In some embodiments, R is —(CH 2 ) 2 CN.

[0391] In some embodiments, R is optionally substituted C 3-30 In some embodiments, R is an optionally substituted C 3-20 In some embodiments, R is an optionally substituted C 3-10 In some embodiments, R is an optionally substituted cyclohexyl. In some embodiments, R is an optionally substituted cyclohexyl. In some embodiments, R is an optionally substituted cyclopentyl. In some embodiments, R is an optionally substituted cyclopentyl. In some embodiments, R is an optionally substituted cyclobutyl. In some embodiments, R is an optionally substituted cyclopropyl. In some embodiments, R is an optionally substituted cyclopropyl.

[0392] In some embodiments, R is an optionally substituted 3-30 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 3 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 4 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 5 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 6 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 7 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted cycloheptyl. In some embodiments, R is cycloheptyl. In some embodiments, R is an optionally substituted cyclohexyl. In some embodiments, R is cyclohexyl. In some embodiments, R is optionally substituted cyclopentyl. In some embodiments, R is cyclopentyl. In some embodiments, R is optionally substituted cyclobutyl. In some embodiments, R is cyclobutyl. In some embodiments, R is optionally substituted cyclopropyl. In some embodiments, R is cyclopropyl.

[0393] In some embodiments, when R is or includes a ring structure (e.g., alicyclic, cycloheteroaliphatic, aryl, heteroaryl, etc.), the ring structure can be monocyclic, bicyclic, or polycyclic. In some embodiments, R is or includes a monocyclic structure. In some embodiments, R is or includes a bicyclic structure. In some embodiments, R is or includes a polycyclic structure.

[0394] In some embodiments, R is an optionally substituted C having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. 1-30In some embodiments, R is an optionally substituted C alkyl group having 1 to 10 heteroatoms. 1-20 In some embodiments, R is an optionally substituted C alkyl group having 1 to 10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, or silicon, and optionally including one or more oxidized forms of nitrogen, sulfur, phosphorus, or selenium. 1-20 In some embodiments, R is independently: [ka] , -N=, ≡N, -S-, -S(O)-, -S(O)2-, -O-, =O, [ka] optionally substituted C containing 1 to 10 groups selected from 1-30 It is heteroaliphatic.

[0395] In some embodiments, R is optionally substituted C 6-30 In some embodiments, R is aryl. In some embodiments, R is substituted phenyl. In some embodiments, R is phenyl. In some embodiments, R is substituted phenyl.

[0396] In some embodiments, R is an optionally substituted 8-10 membered bicyclic saturated ring, partially unsaturated ring, or aryl ring. In some embodiments, R is an optionally substituted 8-10 membered bicyclic saturated ring. In some embodiments, R is an optionally substituted 8-10 membered bicyclic partially unsaturated ring. In some embodiments, R is an optionally substituted 8-10 membered bicyclic aryl ring. In some embodiments, R is optionally substituted naphthyl.

[0397] In some embodiments, R is an optionally substituted 5-30 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is an optionally substituted 5-30 membered heteroaryl ring having 1-10 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, R is an optionally substituted 5-30 membered heteroaryl ring having 1-5 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is an optionally substituted 5-30 membered heteroaryl ring having 1-5 heteroatoms independently selected from oxygen, nitrogen, and sulfur.

[0398] In some embodiments, R is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an unsubstituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, sulfur, and oxygen. In some embodiments, R is a substituted 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an unsubstituted 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0399] In some embodiments, R is an optionally substituted 5-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R is an optionally substituted 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0400] In some embodiments, R is an optionally substituted 5-membered monocyclic heteroaryl ring having one heteroatom selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted pyrrolyl, furanyl, or thienyl.

[0401] In some embodiments, R is an optionally substituted 5-membered heteroaryl ring having two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 5-membered heteroaryl ring having one nitrogen atom and an additional heteroatom independently selected from sulfur or oxygen. In some embodiments, R is an optionally substituted 5-membered heteroaryl ring having three heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 5-membered heteroaryl ring having four heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0402] In some embodiments, R is an optionally substituted 6-membered heteroaryl ring having 1 to 4 nitrogen atoms. In some embodiments, R is an optionally substituted 6-membered heteroaryl ring having 1 to 3 nitrogen atoms. In other embodiments, R is an optionally substituted 6-membered heteroaryl ring having 1 to 2 nitrogen atoms. In some embodiments, R is an optionally substituted 6-membered heteroaryl ring having 4 nitrogen atoms. In some embodiments, R is an optionally substituted 6-membered heteroaryl ring having 3 nitrogen atoms. In some embodiments, R is an optionally substituted 6-membered heteroaryl ring having 2 nitrogen atoms. In certain embodiments, R is an optionally substituted 6-membered heteroaryl ring having 1 nitrogen atom.

[0403] In certain embodiments, R is an optionally substituted 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 5,6-fused heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 6,6-fused heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0404] In some embodiments, R is a 3-30 membered heterocycle having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is a 3-30 membered heterocycle having 1-10 heteroatoms independently selected from oxygen, nitrogen, and sulfur. In some embodiments, R is a 3-30 membered heterocycle having 1-5 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus, and silicon. In some embodiments, R is a 3-30 membered heterocycle having 1-5 heteroatoms independently selected from oxygen, nitrogen, and sulfur.

[0405] In some embodiments, R is an optionally substituted 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is a substituted 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an unsubstituted 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 5- to 7-membered partially unsaturated monocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 5- to 6-membered partially unsaturated monocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 5-membered, partially unsaturated monocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 6-membered, partially unsaturated monocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In certain embodiments, R is an optionally substituted 7-membered, partially unsaturated monocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 3-membered heterocyclic ring having 1 heteroatom independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R is an optionally substituted 4-membered heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 5-membered heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 6-membered heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 7-membered heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0406] In some embodiments, R is an optionally substituted 3-membered saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 4-membered saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is an optionally substituted 5-membered saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some emb...

Claims

1. A drug, an antibody binding moiety; a target binding moiety; and optionally a linker moiety; The agent, wherein the target binding moiety specifically binds to CD38.

2. The agent has the structure of Formula I: 【Chemistry 1】 or a pharmaceutically acceptable salt thereof, wherein: each of a and b is independently 1 to 200; each ABT is independently an antibody binding moiety; L is a linker moiety connecting ABT and TBT, The agent of claim 1 , wherein each TBT is independently a target binding moiety.

3. The agent has the following structure: 【Chemistry 2】 or a pharmaceutically acceptable salt thereof, wherein: each of a and b is independently 1 to 200; each ABT is independently an antibody binding moiety; L is a bivalent linker moiety connecting ABT and TBT; each Xaa is independently a residue of an amino acid or amino acid analog; y is 5 to 20; L Ｔ are linker moieties that each independently connect two residues from an amino acid or amino acid analog, and are independently a covalent bond or C １ -C ６ Aliphatic or C with 1 to 5 heteroatoms １ -C ６ heteroaliphatic, wherein one or more methylene units of the group are optionally and independently -C(R') ２ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ substituted with —N(R′)—, —C(O)S—, or —C(O)O—; Each R ｃ are independently -L ａ -R', t is 0 to 50; Each L ａ are independently a covalent bond, or C １ -C ５０ Aliphatic or C with 1 to 5 heteroatoms １ -C ５０ heteroaliphatic, wherein one or more methylene units of said group are optionally and independently -C(R') ２ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ substituted with —N(R′)—, —C(O)S—, or —C(O)O—; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C ３－２０ Alicyclic ring, C ６－２０ an aryl ring, a 5- to 20-membered heteroaryl ring having 1 to 10 heteroatoms, and a 3- to 20-membered heterocyclyl ring having 1 to 10 heteroatoms; Each R' is independently -R, -C(O)R, -CO ２ R, or -SO ２ R, Each R is independently —H or C １－３０ Aliphatic, C with 1-10 heteroatoms １－３０ Heteroaliphatic, C ６－３０ Aryl, C ６－３０ Arylaliphatic, C with 1-10 heteroatoms ６－３０ an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms, and 3-30 membered heterocyclyl having 1-10 heteroatoms; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with said atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to that atom, 0-10 heteroatoms; or 2. The agent of claim 1, wherein two or more R groups on two or more atoms optionally and independently, together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to said intervening atoms, 0-10 heteroatoms.

4. A drug, an antibody binding moiety; a target binding moiety; and optionally a linker moiety; The target binding moiety has the following structure: 【Transformation 3】 or a salt thereof, wherein each Xaa is independently a residue of an amino acid or amino acid analog; y is 5 to 20; L Ｔ are linker moieties that each independently connect two residues from an amino acid or amino acid analog, and are independently a covalent bond or C １ -C ６ Aliphatic or C with 1 to 5 heteroatoms １ -C ６ heteroaliphatic, wherein one or more methylene units of the group are optionally and independently -C(R') ２ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ substituted with —N(R′)—, —C(O)S—, or —C(O)O—; Each R ｃ are independently -L ａ -R', t is 0 to 50; Each L ａ are independently a covalent bond, or C １ -C ５０ Aliphatic or C with 1 to 5 heteroatoms １ -C ５０ heteroaliphatic, wherein one or more methylene units of said group are optionally and independently -C(R') ２ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ２ -, -S(O) ２ substituted with —N(R′)—, —C(O)S—, or —C(O)O—; Each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently C ３－２０ Alicyclic ring, C ６－２０ an aryl ring, a 5- to 20-membered heteroaryl ring having 1 to 10 heteroatoms, and a 3- to 20-membered heterocyclyl ring having 1 to 10 heteroatoms; Each R' is independently -R, -C(O)R, -CO ２ R, or -SO ２ R, Each R is independently —H or C １－３０ Aliphatic, C with 1-10 heteroatoms １－３０ Heteroaliphatic, C ６－３０ Aryl, C ６－３０ Arylaliphatic, C with 1-10 heteroatoms ６－３０ an optionally substituted group selected from arylheteroaliphatic, 5-30 membered heteroaryl having 1-10 heteroatoms, and 3-30 membered heterocyclyl having 1-10 heteroatoms; or two R groups, optionally and independently, together form a covalent bond; or two or more R groups on the same atom optionally and independently combine with said atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to said atom, 0-10 heteroatoms; or An agent in which two or more R groups on two or more atoms optionally and independently, together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having 0-10 heteroatoms in addition to said intervening atoms.

5. -(Xaa)y- is -Xaa Ｔ１ -Xaa Ｔ２ -(Xaa)y'-Xaa Ｔ３ -Xaa Ｔ４ -Xaa Ｔ５ -comprising During the ceremony, y' is 0 to 8; Xaa Ｔ１ The side chain is C １ -C ８ aliphatically substituted amino acid or amino acid analogue residues, Xaa Ｔ２ is a group in which the side chain contains an optionally substituted aromatic group or is an optionally substituted C ３ -C ８ a residue of an amino acid or amino acid analog that is aliphatic, Xaa Ｔ３ is a C optionally substituted side chain ２ -C ８ a residue of an amino acid or amino acid analog that is aliphatic, Xaa Ｔ４ is a group in which the side chain contains an optionally substituted aromatic group or is an optionally substituted C ３ -C ８ a residue of an amino acid or amino acid analog that is aliphatic, Xaa Ｔ５ The side chain is C １ -C ８ 5. The agent of claim 4, which is an aliphatically substituted amino acid or amino acid analogue residue.

6. Xaa Ｔ１ The agent of claim 5 , wherein is a residue of Ahp, Y, W, S, K, or K(MePEG4c).

7. Xaa Ｔ２ is a residue of Y, W, Ahp, Bph, L, or A.

8. Xaa Ｔ３ The agent of claim 7, wherein is a residue of L, Ahp, V, T, Hse, or MetO2.

9. Xaa Ｔ４ The agent of claim 8, wherein is a residue of Bph, V, or Ahp.

10. Xaa Ｔ５ 10. The agent of claim 9, wherein is a residue of Ahp, Bph, Ado, Ano, PhNle, or PhNva.

11. -(Xaa)y- is -(Xaa) ａ１ -(Xaa) ａ２ -(Xaa) ａ３ -(Xaa) ａ４ -(Xaa) ａ５ -(Xaa) ａ６ -(Xaa) ａ７ -(Xaa) ａ８ -(Xaa) ａ９ -(Xaa) ａ１０ -(Xaa) ａ１１ -(Xaa) ａ１２ -(Xaa) ａ１３ -is or includes, During the ceremony, each of a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, a12, and a13 independently represents 0 to 5; (Xaa) ａ３ is Xaa Ｔ１ is or contains (Xaa) ａ４ is Xaa Ｔ２ is or contains (Xaa) ａ９ is Xaa Ｔ３ is or contains (Xaa) ａ１０ is Xaa Ｔ４ is or contains (Xaa) ａ１１ is Xaa Ｔ５ 11. The method of claim 10, which is or comprises:

12. (Xaa) ａ１ The agent of claim 11, wherein is or comprises A, K, or K(MePEG4c).

13. (Xaa) ａ２ 13. The agent of claim 12, wherein is or comprises R, S, D, Y, A, W, K, 4Py2NH2, Cit, F3G, hCit, K(MePEG4c), RNdMe, RNMe, or RNNdMe.

14. (Xaa) ａ５ The agent of claim 13, wherein is or comprises H, Y, S, L, A, W, or W6N.

15. (Xaa) ａ６ is or comprises D, G, R, Y, H, W, A, or Y.

16. (Xaa) ａ７ 16. The agent of claim 15, wherein is or includes G, D, E, Q, N, R, MetO2, S, Har, or A.

17. (Xaa) ａ８ is or comprises V, A, D, G, W, S, or T.

18. (Xaa) ａ１２ The agent of claim 17, wherein is or comprises D, A, S, G, or Ahp.

19. (Xaa) ａ１３ The agent of claim 18, wherein is or comprises C.

20. -(Xaa)y- is -Xaa Ｔ６ -(Xaa)y'-Xaa Ｔ７ -Xaa Ｔ８ -Xaa Ｔ９ -Xaa Ｔ１０ -Xaa Ｔ１１ - includes During the ceremony, y' is 0 to 8; Xaa Ｔ６ The side chain is C １ -C ８ aliphatically substituted amino acid or amino acid analogue residues, Xaa Ｔ７ is a C optionally substituted side chain ２ -C ８ a residue of an amino acid or amino acid analog that is aliphatic, Xaa Ｔ８ is a residue of proline or an amino acid analog thereof, Xaa Ｔ９ is a group in which the side chain contains an optionally substituted aromatic group or is an optionally substituted C １ -C ８ a residue of an amino acid or amino acid analog that is aliphatic, Xaa Ｔ１０ is a C with a substituted side chain １ -C ８ a residue of an aliphatic amino acid or amino acid analog, or an amino acid residue in which the amino group is substituted, Xaa Ｔ１１ is a group in which the side chain contains an optionally substituted aromatic group or is an optionally substituted C １ -C ８ The agent of claim 4, which is a residue of an amino acid or amino acid analog that is aliphatic.

21. Xaa Ｔ６ is a residue of MeF, L, or S.

22. Xaa Ｔ７ 22. The agent of claim 21, wherein is a residue of L or MeF.

23. Xaa Ｔ８ The agent of claim 22, wherein is a residue of P.

24. Xaa Ｔ９ The agent of claim 23, wherein is a residue of Bph, D, or S.

25. Xaa Ｔ１０ is a residue of V or L.

26. Xaa Ｔ１１ is a residue of W or R.

27. -(Xaa)y- is -(Xaa) ａ１ -(Xaa) ａ２ -(Xaa) ａ３ -(Xaa) ａ４ -(Xaa) ａ５ -(Xaa) ａ６ -(Xaa) ａ７ -(Xaa) ａ８ -(Xaa) ａ９ -(Xaa) ａ１０ -(Xaa) ａ１１ -(Xaa) ａ１２ -is or comprises During the ceremony, each of a1, a2, a3, a4, a5, a6, a7, a8, a9, a10, a11, and a12 independently represents 0 to 5; (Xaa) ａ４ is Xaa Ｔ６ is or contains (Xaa) ａ６ is Xaa Ｔ７ is or contains (Xaa) ａ７ is Xaa Ｔ８ is or contains (Xaa) ａ８ is Xaa Ｔ９ is or contains (Xaa) ａ９ is Xaa Ｔ１０ is or contains (Xaa) ａ１０ is Xaa Ｔ１１ 27. The medicament of claim 26, which is or comprises:

28. (Xaa) ａ１ The agent of claim 27, wherein is or comprises A.

29. (Xaa) ａ２ is or comprises L, A, or P.

30. (Xaa) ａ３ 30. The agent of claim 29, wherein is or comprises H, R, or A.

31. (Xaa) ａ５ The agent of claim 30, wherein is or comprises V, A, or MeG.

32. (Xaa) ａ１１ 32. The agent of claim 31, wherein is or comprises V, A, D, or MeG.

33. (Xaa) ａ１２ The agent of claim 32, wherein is or comprises C.

34. target binding moiety or 【Chemistry 4】 The agent according to claim 4, wherein said peptide is or comprises a sequence selected from SEQ ID NOs: 1 to 34.

35. An agent according to any one of claims 4 to 34, wherein two Xaa are linked together.

36. Two Xaa are —C(O)—CH ２ The agent according to claim 35, which is linked together via a linker having the structure -

37. The agent of claim 36, wherein -C(O)- is bonded to the amino group of Xaa.

38. -CH ２ The agent according to claim 37, wherein - is bonded to -S- in the side chain of Xaa.

39. target binding moiety or 【Transformation 5】 but, 【Chemistry 6-1】 【Chemistry 6-2】 【Transformation 6-3】 5. The agent according to claim 4, which is or comprises: or a salt form thereof.

40. The agent of any one of claims 4 to 34, wherein the antibody binding moiety is capable of binding to two or more antibodies having different Fab regions.

41. The agent of any one of claims 4 to 34, wherein the antibody binding moiety has the structure DCAWHLGELVWCT or a salt form thereof, and the two C residues are linked by -S-S-.

42. The antibody binding moiety is optionally substituted 【Transformation 7】 35. The medicament according to any one of claims 4 to 34, which is or comprises:

43. the antibody binding moiety, 【Transformation 8】 35. The medicament according to any one of claims 4 to 34, which is or comprises:

44. 10. The agent according to any one of the preceding claims, comprising a linker.

45. The linker is -(CH ２ CH ２ 0) An agent according to any one of the preceding claims which is or comprises n-, wherein n is 1 to 20.

46. 10. The agent of any one of the preceding claims, wherein the linker comprises one or more amino acid residues.

47. The linker is 【Chemistry 9】 10. The medicament according to any one of the preceding claims, comprising:

48. The agent is I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-18, I-19, I-24, I-25, I-26, I-27, I-28, I-29, I-30, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41, I-42, I-43, I-44, I-45, I-46, or I-47, or a pharmaceutically acceptable salt thereof.

49. 10. The agent of any one of the preceding claims, wherein the agent binds to CD38 with a Kd of 200, 100, 50, 40, 30, 20, 10, or 5 nM or less as measured by SPR.

50. A composition comprising an agent according to any one of the preceding claims and a cell population.

51. 51. The composition of claim 50, wherein the cells are or comprise NK cells, engineered NK cells, ex vivo expanded NK cells, memory-like NK cells, cytokine-induced memory-like NK cells, NKT cells, monocytes, and / or macrophages.

52. A pharmaceutical composition comprising an agent or composition according to any one of the preceding claims and a pharmaceutically acceptable carrier.

53. The composition of any one of claims 50 to 52, wherein the composition comprises an immunoglobulin.

54. 54. The composition of claim 53, wherein the immunoglobulin is an intravenous immunoglobulin.

55. A method for treating a CD38-associated condition, disorder, or disease, comprising administering to a subject suffering therefrom an effective amount of an agent or composition described in any one of the preceding claims.

56. 56. The method of claim 55, comprising administering the cell population to a subject.

57. 57. The method of claim 56, wherein the subject is subjected to both the agent or composition and the cell population.

58. 58. The method of claim 56 or 57, wherein the cells are or comprise NK cells, engineered NK cells, ex vivo expanded NK cells, memory-like NK cells, cytokine-induced memory-like NK cells, NKT cells, monocytes, and / or macrophages.

59. 59. The method of any one of claims 56 to 58, wherein the cells are administered simultaneously with the agent or composition.

60. 60. The method of any one of claims 56 to 59, wherein the cells are administered simultaneously with the agent or composition in a composition comprising the cells and the agent or composition.

61. 59. The method of any one of claims 56 to 58, wherein the cells are administered before or after administration of the agent or composition.

62. 62. The method of any one of claims 55 to 61, wherein the method comprises administration of intravenous immune globulin.

63. 63. The method of claim 62, wherein the immunoglobulin is administered simultaneously with, before, or after the agent or composition.

64. 10. The method of any one of the preceding claims, wherein administration of the agent is followed by one or more doses of a cell of any one of the preceding claims, and / or one or more doses of a cell of any one of the preceding claims and an agent of any one of the preceding claims.

65. 1. A method comprising: a) providing a first compound comprising a target binding moiety as defined in any one of the preceding claims and a first reactive group; b) providing a second compound comprising an antibody binding moiety according to any one of the preceding claims and a second reactive group; c) reacting the first reactive group with the second reactive group so that the target-binding moiety and the antibody-binding moiety are covalently linked.

66. 66. The method of claim 65, wherein the first compound is a compound of formula V or a salt thereof:

67. 67. The method of claim 65 or 66, wherein the second compound is a compound of formula IV, IV-a, IV-b, IV-c, or IV-d, or a salt thereof.

68. 10. A method for producing an agent or composition according to any one of the preceding claims, comprising reacting a first compound comprising an antibody binding moiety and an alkyne with a second compound comprising a target binding moiety and an azide, or reacting a first compound comprising an antibody binding moiety and an azide with a second compound comprising a target binding moiety and an alkyne.

69. A method for recruiting antibodies to a target containing or expressing CD38, comprising contacting the target with an agent or composition described in any one of the preceding claims.

70. A method for recruiting immune activity to a target containing or expressing CD38, comprising contacting the target with an agent according to any one of the preceding claims.

71. 71. The method of claim 69 or 70, wherein the target is a tumor cell.

72. A compound, agent, composition, or method according to any one of embodiments 1 to 367.

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