73 results about "Prostate specific membrane" patented technology

A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula (I) or of a salt or a solvate thereof. R1 is —R1aR1b— wherein R1a is absent, —CH2—, —O—, or —S—, and R1b is —CH2— or —CHF—. R2 is —(CH2)3—O—, —(CH2)3—, —(CH2)4—, —CH2—O—(CH2)2—, or —CH2—S—(CH2)2. R3 is ethylene fused to a tricyclic fused ring. L1, L2, L3, L4, L5b L5c, L6 and L7 are linkages (e.g. peptide bonds). Xbr is a branching atom. Rrad is a radiometal chelator. Ralb is an albumin binder. n1, n2, n3, n4, and n5 are integers. When the PSMA-targeting moiety is linked to a radiolabeling group, the compound may be used as an imaging agent or therapeutic agent for PSMA-expressing diseases / conditions.

A prostate-specific membrane antigen (PSMA)-targeting conjugate having a phosphonate backbone, which is used for tumor detection after chelation of a diagnostic nuclide and is used for radiation therapy after being combined with a treatment-type nuclide. A conjugate nuclide chelation part is replaced with a fluorescent probe or a cytotoxic drug so that the PSMA-targeting conjugate can then be used for diagnosis and treatment of diseases.

The present invention relates to a compound of formula (1) or a pharmaceutically acceptable salt or solvate thereof, wherein Y3 is O or S, wherein s, t, u and w are, independently of each other, 0 or 1, wherein i is an integer of from 1 to 3, wherein j is an integer of from 3 to 5, and wherein Z1, Z2 and Z3 are independently of each other, selected from the group consisting of CO2H, -SO2H, -SO3H, -OSO3H, and -OPO3H2,, R1 is -CH3 or H, preferably H, X is selected from the group consisting of alkylaryl, aryl, alkylheteroaryl and heteroaryl, Y1 and Y2 are independently, of each other, selected from the group consisting of aryl, alkylaryl, cycloalkyl, heterocycloalkyl, heteroaryl and alkylheteroaryl, and wherein A is a chelator residue having a structure selected from the group consisting of (Ia), (Ib) and (Ic) wherein R2, R3, R4 and R5 are, independently of each other, selected from the group consisting of H, - CH2-COOH and -CH2-C(=O)-NH2 or wherein R2 and R4 form a -(CH2)n- bridge with n being an integer of from 1 to 3, wherein n is preferably 2, and wherein r, v and q, are independently of each other, 0 or 1, with the proviso that in case u and w are 0, q and v are 0, and (A) wherein u and w are 1, or (B) wherein u is 0 and w is 1, and wherein A is selected from (Ia) or (Ib), or (C) wherein A is not Further, the present invention relates to a complex comprising (a) a radionuclide, and (b) the compound, as described above or below, or a salt, solvate, metabolite or prodrug thereof. Further, the present invention relates to a pharmaceutical composition comprising a compound, as described above or below, or a complex, as described above or below. Further, the present invention relates to a compound, as described above or below, or a complex, as described above or below, or a pharmaceutical composition, as described above or below, for use in treating, ameliorating or preventing PSMA-expressing cancer and / or metastases thereof, in particular prostate cancer and / or metastases thereof. Further, the present invention relates to a compound, as described above or below, or a complex, as described above or below, or a pharmaceutical composition, as described above or below, for use in diagnostics. In addition, the present invention relates to a compound, as described above or below, or a complex, as described above or below, or a pharmaceutical composition, as described above or below, for use in the diagnosis of cancer, in particular of PSMA-expressing cancer and / or metastases thereof, in particular prostate cancer and / or metastases thereof.

An inhibitor of a prostate specific membrane antigen and a pharmaceutical use thereof. Specifically, the present solution belongs to the field of radiopharmaceuticals and relates to a compound represented by formula (IV) or a pharmaceutically acceptable salt thereof.

The present disclosure provides methods for treating prostate cancer or metastatic castration-resistant prostate cancer, reducing the severity of prostate cancer or metastatic castration-resistant prostate cancer, or inhibiting the growth of prostate cancer or metastatic castration-resistant prostate cancer. The methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody, or antigen-binding fragment thereof, that specifically binds to prostate specific membrane antigen (PSMA) and CD28, as a monotherapy or in combination with an anti-PD1 antibody.

The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and / or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following:or a pharmaceutically acceptable salt thereof,or a pharmaceutically acceptable salt thereof,or a pharmaceutically acceptable salt thereof,wherein M1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

Theranostic agents incorporating a chelating moiety that can chelate a radioactive metal isotope and a PSMA-targeting moiety are disclosed herein. The theranostic agents, which can be used to treat and / or detect cancers associated with increased PSMA expression, have the formula:and include complexes, anions or salts thereof. R1 includes a chelating moiety; a is 0 or 1; n is an integer from 12 to 21; and R2 includes a prostate specific membrane antigen (PSMA)-targeting moiety. Optionally, the chelating moiety is chelated to a metal atom, where the metal atom is a positron or single photon emitting metal isotope, or an alpha, beta, or Auger emitting metal isotope.

The invention discloses a preparation method and application of a targeting small molecule (ACUPA) coupled nano drug delivery system (AMC) specifically combined with prostate specific membrane antigen (PSMA), and belongs to the technical field of biological medicine. The targeting micromolecule (ACUPA) coupled nano drug-loaded delivery system (AMC) is a targeting micromolecule coupled nano drug-loaded polymer micelle which can be specifically combined with prostate specific membrane antigen (PSMA). The micelle is formed by self-assembly through a film hydration method. The targeting micromolecule (ACUPA) specifically bound with the prostate specific membrane antigen (PSMA) is coupled with the polymer micelle through a chemical bond. The targeting micromolecule (ACUPA) can be specifically combined with prostate cancer cells expressing PSMA, a nano drug-loaded preparation is delivered to the prostate cancer cells, the active targeting property of combination with a specific antigen, the endothelial action of the antigen cells and the high-permeability long-retention effect of the nano preparation are fully exerted, multiple effects are synergistic, and the drug-loaded nano drug-loaded preparation is prepared. The toxicity of the medicine on prostate cancer cells is remarkably increased, and then the targeted therapy of prostate cancer is enhanced.

To provide new compounds that can be used for the treatment of various disease states of prostate specific membrane antigen (PSMA) expressing cancers.SOLUTION: For example, provided is a complex comprising a compound of Formula CA009 as shown in the Figures, or pharmaceutically acceptable salts or solvates thereof, and a radionucleide selected from 203Pb and 212Pb.SELECTED DRAWING: Figure 1-10

The present invention relates to polyplexes comprising linear conjugates of LPEI and PEG. The LPEI and PEG fragments of the linear conjugates are preferably linked by a [3+2]cycloaddition between an azide and an alkene or an alkyne to produce a 1, 2, 3 triazole or a 4,5-dihydro-1H-[1,2,3]triazole. The linear conjugates are further conjugated to a targeting fragment capable of binding to prostate specific membrane antigen (PSMA) to enable selective interaction with a particular cell type. The conjugates can form polyplexes with therapeutic agents such as nucleic acids to deliver the therapeutic agents to cells.

The present application provides a marker inhibitor for diagnosing or treating a cancer expressing prostate-specific membrane antigen, the inhibitor being a compound represented by general formula I or a compound represented by general formula II or a compound represented by general formula III or an optical isomer, a pharmaceutically acceptable salt and / or a solvate thereof, and the present application also provides a preparation method thereof and a pharmaceutical composition containing the compound. The present application also relates to the use of the compound and a pharmaceutically acceptable salt, a solvate or a prodrug thereof in treatment as a therapeutic agent for treating a cancer expressing PSMA.

The present invention is directed to a conjugate including: (i) an antigen-binding polypeptide having a specific binding affinity to prostate specific membrane antigen (PSMA); and (ii) a benzylguanidine prosthetic group including a radionuclide, wherein (i) and (ii) are covalently bound. Further provided are a composition including the conjugate, and use of same, such as in a theranostic method.

The present disclosure provides multispecific antigen-binding molecules that bind to prostate specific membrane antigen (PSMA) and 4-1BB (anti-PSMA x anti-4-1BB). In certain embodiments, the present disclosure provides a multispecific anti-PSMA x anti-4-1BB antigen-binding molecule or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds PSMA, a second antigen-binding domain that specifically binds 4-1BB, and a third antigen-binding domain that specifically binds 4-1BB. In certain embodiments, the molecules are multispecific antibodies or antigen-binding fragments thereof. In certain embodiments, the multispecific antibodies disclosed herein bind PSMA expressed on tumor cells with the first antigen-binding domain and 4-1BB on immune cells (e.g., T cells) with the second and third antigen-binding domains. In certain embodiments, the antibodies of the present disclosure are useful in treatment of a cancer. In certain embodiments, the antibodies are useful for treating a PSMA-associated disease or disorder (e.g., prostate cancer).

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer. Thus, the present invention concerns compounds that are represented by the general Formulae (Ia) or (Ib).

The present invention relates to a dual antigen-targeting protein complex comprising an antibody or its antigen-binding fragment and an affibody. More specifically, the dual antigen-targeting protein complex comprises an EGFR (Epidermal Growth Factor Receptor) or PSMA (Prostate Specific Membrane Antigen) target site containing an antibody or its antigen-binding fragment, and a CD137 target site containing an affibody bound to the antibody or its antigen-binding fragment. When the dual antigen-targeting protein complex or a composition containing it is used, cancer can be effectively prevented or treated.

Provided herein, inter alia, are antigen-binding molecules having binding specificity for differentiation population 3T cell receptors (CD3); an antigen binding molecule having binding specificity for prostate specific membrane antigen (PSMA); a cleavable linker sequence; and a protease activatable bispecific fusion protein, such as a protease activatable T cell adapter; as well as uses and methods of treatment.

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of PSMA-expressing cancers, especially prostate cancer, and metastases thereof. In particular, the present invention relates to a PSMA binding ligand or a pharmaceutically acceptable salt or solvate thereof as well as to the use of said PSMA binding ligand, the PSMA binding ligand comprising a PSMA binding motif Q and a chelator residue A linked via at least one linker LAQ comprising at least one, optionally N-alkylated, neutral amino acid Xi.

The present disclosure provides multispecific antigen-binding molecules that bind to prostate specific membrane antigen (PSMA) and 4-1 BB (anti-PSMA x anti-4-1 BB). In certain embodiments, the present disclosure provides a multispecific anti-PSMA x anti-4-1 BB antigenbinding molecule or antigen-binding fragment thereof comprising a first antigen-binding domain that specifically binds PSMA, a second antigen-binding domain that specifically binds 4-1 BB, and a third antigen-binding domain that specifically binds 4-1 BB. In certain embodiments, the molecules are multispecific antibodies or antigen-binding fragments thereof. In certain embodiments, the multispecific antibodies disclosed herein bind PSMA expressed on tumor cells with the first antigen-binding domain and 4-1 BB on immune cells (e.g., T cells) with the second and third antigen-binding domains. In certain embodiments, the antibodies of the present disclosure are useful in treatment of a cancer. In certain embodiments, the antibodies are useful for treating a PSMA-associated disease or disorder (e.g., prostate cancer).

The present disclosure provides methods for treating clear cell renal cell carcinoma (ccRCC) or metastatic ccRCC, reducing the severity of ccRCC or metastatic ccRCC, or inhibiting the growth of ccRCC or metastatic ccRCC. The methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody or antigen-binding fragment thereof, the bispecific antibody or antigen-binding fragment thereof specifically binding to prostate specific membrane antigen (PSMA) and CD28.

The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and / or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following:or a pharmaceutically acceptable salt thereof,or a pharmaceutically acceptable salt thereof,or a pharmaceutically acceptable salt thereof,wherein M1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

The invention relates to a multi-target molecular ligand as well as a preparation method and application thereof. The multi-targeting molecular ligand disclosed by the invention aims at prostate cancer and bone metastasis thereof, and the ligand simultaneously contains a polypeptide chain Glu-urea-Lys (ACUPA) capable of being recognized by a prostate specific membrane antigen (PSMA), is used for targeting diphosphoric acid of hydroxyapatite nanocrystals in bones, and is also combined with an anisidine fragment which is specifically combined with a Sigma-1 receptor. The multi-target molecular ligand can efficiently mark radionuclide and has excellent radiation stability, cell and animal experiments prove that the multi-target molecular ligand can be efficiently taken by PSMA positive prostate cancer RM-1 cells, RM-1 subcutaneous tumor models and RM-1 tibial metastatic tumor models, and can be used for developing diagnosis and treatment of PSMA positive prostate cancer and bone metastasis thereof, and diagnosis and treatment integration is achieved.

The invention relates to a new class of compounds that can serve as prostate specific membrane antigen (PSMA) ligands, and to precursors to this class. The precursors have an amine that is available for functionalisation. Derivatives of the compounds are useful for imaging and therapy of cancer.

Provided herein are methods of treating brain cancer in a subject, comprising evaluating one or more biological samples from a subject who has brain cancer for the presence of a miRNAs and administering interleukin-12 (IL-12); an immunogenic composition of human telomerase reverse transcriptase (hTERT), Wilms Tumor-1 (WT-1), and prostate specific membrane antigen (PSMA); and an anti-programmed cell death receptor 1 (PD-1) antibody to said subject if the subject has an increased expression level of the mIR-331-3p miRNA or isomiRs thereof and the miR-1537-3p miRNA or isomiRs thereof relative to a control population of subjects. Also provided herein are methods of treating brain cancer in a subject, comprising measuring an expression level of at least one mRNA biomarker selected from SYNGR3, OTX1, GABBR2, LHX1, CADM3, MLLT11, MNX1, GRB14, SLC34A2, PHYHIP, WNT10B, SLC17A6, CRLF1, HOXD13, TGFβR3, UBA7, SFRP4, or any combination thereof, in a tumor sample from a subject and administering IL-12; an immunogenic composition hTERT, WT-1, and PSMA; and an anti-PD-1 antibody to said subject if the expression level of SYNGR3, OTX1, GABBR2, LHX1, CADM3, MLLT11, MNX1, GRB14, SLC34A2, PHYHIP, WNT10B, SLC17A6, CRLF1 and HOXD13 is decreased or if the expression level of TGFβR3, UBA7, SFRP4 is increased.

The invention relates to a polypeptide nano-protein ubiquitination degradation agent as well as a preparation method and application thereof. The polypeptide nano-protein ubiquitination degradation agent comprises an androgen receptor protein binding unit, a connexon and an E3 ligase recognition unit which are sequentially connected, wherein the connexon is further sequentially connected with a self-assembly unit and a tumor cell targeting unit; the tumor cell targeting unit comprises a ligand of a prostate specific membrane antigen. The polypeptide nano protein ubiquitination degradation agent can realize self-assembly in cells, androgen receptor protein and E3 ligase can be adaptively combined to sites with proper distance and steric hindrance, the ubiquitination degradation function is played, and the non-concentration dependence of micromolecule PROTAC protein degradation is broken.

Provided herein are methods of treating prostate cancer using radiopharmaceuticals. The radiopharmaceuticals compositions can comprise a prostate specific membrane antigen (PSMA) targeting moiety, a metal chelator, and a radionuclide chelated to the metal chelator.

The invention relates to the field of nuclear medicine, in particular to a prostate specific membrane antigen small-molecule inhibitor and preparation and application of a radionuclide complex of the prostate specific membrane antigen small-molecule inhibitor. The prostate specific membrane antigen small-molecule inhibitor has a structure as shown in a general formula (I). The invention also provides a radionuclide complex containing radionuclide and the prostate specific membrane antigen small-molecule inhibitor. On the basis of a prostate specific membrane antigen small-molecule inhibitor, various medical radionuclides, such as a complex formed by 68Ga or 177Lu, are marked, and the complex can be respectively used for PSMA specific SPECT / CT (Single Photon Emission Computed Tomography / Computed Tomography), PET / CT (Positron Emission Tomography / Computed Tomography) imaging or prostate cancer treatment. The complex has the characteristics of high labeling rate, good stability, good tumor tissue targeting property and the like, provides a new idea for diagnosis and treatment integration of prostate cancer, and has a wide application prospect.

The invention belongs to the technical field of radiopharmaceutical chemistry and clinical nuclear medicine, and particularly relates to a glutamic acid-ureido-lysine compound containing an L-proline derivative as well as a preparation method and application of the glutamic acid-ureido-lysine compound. A radioactive preparation obtained by labeling the glutamic acid-ureido-lysine compound containing the L-proline derivative with radionuclide can be specifically combined with a prostate specific membrane antigen target spot, has high uptake at a tumor site with high expression of a prostate specific membrane antigen, has a good tumor / non-target ratio, and can be used for preparing a prostate specific membrane antigen. The medicine is a novel tumor radiopharmaceutical with popularization and application values.

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer. Thus, the present invention concerns compounds that are represented by the general Formulae (Ia) or (Ib).