ERIBULINE DRUG CONJUGATE

Abstract

A conjugate of the Eribulin drug or a pharmaceutically acceptable salt or solvate thereof, and a preparation method therefor and the use thereof; a linker-drug conjugate or an isomer, mesomer, racemate, or an enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt or solvate thereof, and a preparation method therefor and the use thereof; and a cytotoxin or an isomer, mesomer, racemate, or an enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt or solvate thereof, and a preparation method therefor and the use thereof.

Description

Eribulin Drug Conjugate CROSS-REFERENCE TO RELATED REQUESTS

[001] The present invention is based on, and claims priority to, Patent Applications CN No. 202310082754.5, filed on January 17, 2023, CN No. 202310563948.7, filed on May 18, 2023, and CN No. 2024100454262, filed on January 11, 2024. The entirety of each of which is incorporated herein by reference. TECHNICAL FIELD

[002] The present invention relates to the technical field of medicine, in particular to a drug-ligand conjugate, a drug-ligand compound, and their methods of preparation and uses. BACKGROUND

[003] As a specific treatment that can target cancer cells, the development of ADCs (antibody-drug conjugates) has made significant progress since 2000. Currently, there are 15 ADC drugs on the market worldwide, namely: Mylotarg, Besponsa, KADCyla, Polivy, Lumoxiti, Enhertu, ADCetris, PADCev, Tivdak, Blenrep, Trodelvy, Akalux, Zynlonta, Disitamab Vedotin, and Elahere. Treatment fields focus primarily on hematological tumors and solid tumors. An ADC consists of three main components: a monoclonal antibody or antibody fragment that selectively binds to an antigen on the surface of the tumor cell, a cleavable and non-cleavable ligand, and a small molecule cytotoxin. The ADC makes full use of the specificity of the antibody binding to the tumor cell antigen and the high efficiency of the small molecule drug.

[004] Microtubules are hollow, fibrous filaments composed of α-tubulin and β-tubulin. They are one of the components of the cytoskeleton and play an important role in cell signal transduction. Petition 870250075555, dated 08 / 26 / 2025, page 8 / 279 2 / 177 microtubules play a role in intracellular migration and transport and in maintaining cell shape. Furthermore, during mitosis, microtubules reorganize to form spindles, which are crucial for the movement and separation of sister chromatids. Most biological functions of microtubules in cells are regulated by polymerization kinetics, and interference with the dynamic behavior of microtubules can have a significant impact on spindle formation and cell division. Because cancer cells divide rapidly, they are more sensitive than normal cells to drugs that affect normal tubulin function. Currently, important microtubule inhibitors used as ADC payloads include auristatin and eribulin, which are derived from marine species, and maytansinoids, derived from plants.

[005] Eribulin is a simplified synthetic derivative of the macrocyclic compound Halichondrin B. In November 2010, eribulin (methanesulfonate) was approved by the US FDA for the clinical treatment of patients with metastatic breast cancer who have received at least two chemotherapy regimens (including chemotherapeutic agents such as anthracycline and taxane). Its trade name is Halaven™, developed and marketed by Eisai. Eribulin can selectively bind to the β-tubulin (+) end to inhibit microtubule elongation. In addition to directly killing cancer cells, it can also transform the tumor microenvironment and serve as a small toxin molecule to potentiate the bystander effect of ADCs. The most common adverse reactions to eribulin are fatigue, neutropenia, hair loss, peripheral neuropathy, nausea, constipation, etc.Currently, there are few studies on ADCs with eribulin as the warhead, and all of them show the ligand introduced into the amino group at C35 of eribulin. There are no cases of ligand introduction into the hydroxyl group at C34. Furthermore, there is no research on the use of... Petition 870250075555, dated 08 / 26 / 2025, page 9 / 279 3 / 177 precursor of Eribulin with dihydroxyl groups as the head.

[006] In summary, although eribulin can be used clinically as a single drug, the development of a stable ADC molecule containing eribulin or its derivatives for targeted administration to tumor cells may make treatment safer and more effective and better meet clinical needs. SUMMARY OF THE INVENTION

[007] Based on a comprehensive understanding of ADC drugs, the inventors of the Application creatively designed and synthesized a series of ADC molecules containing eribulin or its derivatives. Through experiments, the designed ADC molecules were found to exhibit good antitumor activity.

[008] In a first aspect, the present application relates to a drug-ligand conjugate of formula I or a pharmaceutically acceptable solvate or salt thereof. Ab-(LD)n Formula 1 in which, Ab is a ligand unit; L is a ligand used to covalently connect Ab to D; n is selected from integers or decimals between 1 and 40; -D is as shown in the formula Ϡ or formula Ϡ: Formula II where W is an oxygen atom or a sulfur atom, Petition 870250075555, dated 08 / 26 / 2025, p. 10 / 279 4 / 177 R1 and R2 are either the same or different, and are each independently selected from: hydrogen atom, alkyl, alkoxy, alkenyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, -C(O)-Q1-Q2 and SO2-Q1-Q2, wherein Q1 is selected from the group consisting of O, N, S atoms and a chemical bond, Q2 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl and heteroaryl; Optionally, the alkyl, alkoxy, alkenyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, aryl, and heteroaryl groups are each independently substituted with one or more substituents selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; or R1 and R2, together with a nitrogen atom connected to them, form a 3- to 8-membered heterocyclyl group;Optionally, the heterocyclyl group is replaced by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms; R3 is selected from the group consisting of hydrogen, alkyl, acyl, sulfonyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms; Optionally, the alkyl, acyl, sulfonyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are each independently substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms.

[009] In some embodiments, L has a structure shown in formula IV; THE Xmz^ p Petition 870250075555, dated 08 / 26 / 2025, p. 11 / 279 5 / 177 Formula IV in which, M is a covalently bonding unit connected to Ab; Z is selected from the group consisting of -C1-C10 alkylene-, -C3-C8 carbocyclo-, -arylene-, 3- to 8-membered heterocyclyl-, (CH2CH2O)r-, sulfonyl, amide, a chemical bond, X2 Y2 and any combinations thereof, where X1 and X2 are selected from the group consisting of -C1-C10 alkylene-, -C3C8 carbocyclo-, -arylene-, 3- to 8-membered heterocyclyl- -(CH2CH2O)r-, -NR4-, carbonyl and any combinations thereof, wherein R4 is selected from the group consisting of hydrogen atom, deuterium atom, alkyl and substituted alkyl; optionally, the 3- to 8-membered -C1C10 alkylene-, -C3-C8 carbocyclo- and heterocyclyl- are each independently substituted with one or more substituents selected from the group consisting of hydrogen atom, deuterium atom, halogen, hydroxyl, cyano, nitro, amino, alkyl, heteroalkyl, substituted alkyl, alkoxy, carboxy and cycloalkyl; each heterocyclyl independently contains 1 to 3 atoms selected from the group consisting of N, O and S; Y1 is a hydrophilic structure selected from the group consisting of carboxyl, phosphoric acid, polyphosphoric acid, phosphoric acid, sulfonic acid, sulfinic acid, polyethylene glycol (PEG), and any combinations thereof; Y2 is selected from Petition 870250075555, dated 08 / 26 / 2025, page 12 / 279 6 / 177 following structures: COOH •O^OH and r is selected from integers between 1 and 10; qi and q2 are selected from integers between 1 and 8; and e is selected from integers between 1 and 20; A is a peptide residue consisting of 2 to 7 amino acids; G is a spacer unit connected to D; ep is 0 or 1.

[0010] In some modes, a wavy line to the left in ouX2 Y2 indicates connection to a binding site in M, and a wavy line to the right indicates connection to a carbonyl.

[0011] In some embodiments, the linking unit M has a succinimide structure as represented by formula a, or a structure as represented by formula b or formula c in which the ring in the succinimide group is in open form: Formula a COOH | HN-jxS o Formula b V / COOH THE Formula c Petition 870250075555, dated 08 / 26 / 2025, p. 13 / 279 7 / 177

[0012] In formula a, formula b, or formula c, a wavy line on the left indicates connection to a binding site on Ab, and a wavy line on the right indicates connection to a binding site on Z.

[0013] In some embodiments, A is a polypeptide residue composed of 2 to 7 amino acids selected from the group consisting of phenylalanine, glycine, valine, lysine, citrulline, serine, glutamic acid, aspartic acid, and cysteic acid.

[0014] In some embodiments, the spacer unit G is selected from the group consisting of structures represented by the formulas Va, Vb, Vc and Vd and any combinations thereof: R5 R6R7 Formula Va R5o I R5' formula Vd wherein a wavy line on the left represents a binding site between a nitrogen atom and peptide residue A, a wavy line on the right represents a binding site between an oxygen atom and drug D, and W is an oxygen atom or a sulfur atom and is a linking group between drug D and spacer unit G; and R5, R5', R6 and R7 are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl and substituted alkyl.

[0015] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by formula VI or formula VII: Petition 870250075555, dated 08 / 26 / 2025, p. 14 / 279 8 / 177 Formula VI Formula VII where Ab, Z, A, R5, R6, R7, R3, and W are as defined above; ni, n2, and n3 are selected independently from integers or decimals between 0 and 40 (e.g., 0-5, 5-10, 10-15, 15-20, 20-25, 25-30, 30-35, or 35-40), m, n2, and n3 are not 0 at the same time, and Petition 870250075555, dated 08 / 26 / 2025, p. 15 / 279 9 / 177 ni+n2+n3< 40.

[0016] In some embodiments, Z is selected from the group consisting of -C1-C10 alkylene-, -(CH2CH2O)r-, amide, X2 Y2, and any combinations thereof;

[0017] In some embodiments, Z is -C2-alkylene or -C5-alkylene;

[0018] In some forms, Z is Y, where q1 is selected from integers between 1 and 8 (for example, 1, 2, 3, 4, 5, 6, and 8).

[0019] In some modalities, q1 is 1.

[0020] In some embodiments, q1 is 1, and -NH-X1-Y1 comprises the hydrophilic structural unit Ac1, Ac1 is selected, without limitation, from the group consisting of (D / L) alanine, (D / L) leucine, (D / L) isoleucine, (D / L) valine, (D / L) phenylalanine, (D / L) proline, (D / L) tryptophan, (D / L) serine, (D / L) tyrosine, (D / L) cysteine, (D / L) cystine, (D / L) arginine, (D / L) histidine, (D / L) methionine, (D / L) asparagine, (D / L) glutamine, (D / L) threonine, (D / L) aspartic acid, (D / L) glutamic acid, derivatives of natural or non-natural amino acids and the following structures: HO OH h ,0H Petition 870250075555, dated 08 / 26 / 2025, p. 16 / 279 10 / 177

[0021] In some embodiments, qi is 1, and -NH-X1-Y1 comprises the hydrophilic structural unit Aci, Aci is selected from the following

[0022] structures: In some modalities, Z is that, q2 is selected from integers between 1 and 8 (for example, 1, 2, 3, 4, 5, 6, 7 and 8); preferably, q2 is 1; preferably, X2 is -(C1C10alkylene)-(CH2CH2O)r-(C=O)- or -(C1-C1oalkylene)-(CH2CH2O)rNR4-.

[0023] In some embodiments, q2 is 1, and -X2-Y2 makes up the hydrophilic structural unit Ac2, Ac2 is selected, without limitation, of D0I0 DtDHo ouHo ; r is selected from integers between 1 and 10 (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10); and e is selected from integers between 1 and 20 (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20).

[0024] In some embodiments, q2 is 1, and -X2-Y2 makes up the hydrophilic structural unit Ac2, Ac2 is selected from the following structures. Petition 870250075555, dated 08 / 26 / 2025, page 17 / 279 11 / 177 turas: HOOCD „ , , , Ί Ο Io AM°-^n-^n-''cooh ^M^nK-'V' λΜ^Ν^ν0COOH ,H0 e

[0025] In some embodiments, A is a polypeptide residue composed of 2 to 5 amino acids selected from the group consisting of phenylalanine, glycine, valine, lysine, citrulline, serine, glutamic acid, aspartic acid, and cysteic acid.

[0026] In some embodiments, A is a peptide residue formed by 2 to 4 amino acids selected from phenylalanine and glycine.

[0027] In some embodiments, A is a tetrapeptide residue composed of glycine (G), glycine (G), phenylalanine (F), and glycine (G).

[0028] In some forms, A is -GGFG-.

[0029] In some embodiments, W is an oxygen atom or a sulfur atom, Ri and R2 are the same or different, and are each independently selected from the group consisting of: hydrogen atom, alkyl, alkoxy, alkenyl, cycloalkyl, -C(O)-Qi-Q2 and -SO2-Q1-Q2, wherein Q1 is selected from the group consisting of O and a chemical bond, and Q2 is selected from the group consisting of alkyl, heterocyclyl, alkenyl, aryl, heteroaryl and cycloalkyl; optionally, the alkyl, heterocyclyl, alkenyl, aryl, heteroaryl and cycloalkyl are each independently substituted by one or more substituents selected from the group consisting of hydrogen atom, alkyl, hydroxyalkyl, halogen, deuterium, mercapto, amino, hydroxy, cycloalkyl and heterocyclyl;or R1 and R2 together with a nitrogen atom connected to them, form a 3- to 6-membered heterocycline, and optionally the heterocycline is substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, aryl, and hydroxyl atoms; R3 is selected from the group consisting of hydrogen and alkyl atoms, and optionally the alkyl is substituted by one or more substituents; Petition 870250075555, dated 08 / 26 / 2025, page 18 / 279 12 / 177 selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, hydroxyl, cycloalkyl and heterocyclyl atoms.

[0030] In some embodiments, W is an oxygen atom, Ri and R2 are the same or different, and are each independently selected from the group consisting of: hydrogen, alkyl, alkenyl, haloalkyl, -C(O)-Qi-Q2 and -SO2-Q1-Q2 atoms, wherein Q1 is selected from the group consisting of O and a chemical bond, Q2 is selected from the group consisting of 3 to 8 membered alkyl, alkenyl, aryl and cycloalkyl, and optionally, the alkyl, alkenyl, aryl and cycloalkyl are each independently substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, halogen, aryl, and hydroxyl atoms;or R1 and R2 together with a nitrogen atom connected to them, form a 3- to 6-membered heterocycline containing one to two nitrogen atoms and optionally an oxygen atom; optionally, the 3- to 6-membered heterocycline is substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, and haloalkyl atoms; R3 is selected from the group consisting of hydrogen and alkyl atoms, and the alkyl is substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, deuterium, amino, and hydroxyl atoms.

[0031] In some embodiments, W is an oxygen atom, R1 and R2 are the same or different, and are each independently selected from the group consisting of: hydrogen atom, C1-C4 alkyl (such as methyl, ethyl), C2-C4 alkenyl (such as allyl), C1-C4 haloalkyl (such as difluoroethyl) and the following structures: Petition 870250075555, dated 08 / 26 / 2025, page 19 / 279 13 / 177 o or R1 and R2, together with a nitrogen atom connected to them, form a 3- to 6-membered heterocycline containing one to two nitrogen atoms and optionally an oxygen atom (such as aziclopropyl, piperidinyl, piperazinyl, morpholinyl); optionally, the 3- to 6-membered heterocycline is substituted with one or more substituents selected from the group consisting of a hydrogen atom, C1-C4 alkyl (e.g., methyl), and C1-C4 haloalkyl (e.g., trifluoromethyl); and R3 is selected from the group consisting of a hydrogen atom and a methyl atom.

[0032] In some embodiments, R5, Re and R7 are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl, haloalkyl, deuterated alkyl and hydroxyalkyl.

[0033] In some embodiments, R5, Re and R7 are simultaneously hydrogen atoms. Petition 870250075555, dated 08 / 26 / 2025, p. 20 / 279 14 / 177

[0034] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by formula VIa or formula VIIa: Formula VIIa where Ri, R2, R3, m, n2 and n3 are as defined above.

[0035] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by formula VIb or formula VIIb: Petition 870250075555, dated 08 / 26 / 2025, p. 21 / 279 15 / 177 Formula VIb Formula VlIb where Ri, R2, R3, ni, n2 and n3 are as defined above;

[0036] Aci is a hydrophilic structural unit having the structure shown in formula d: 'NH The formula for Xi and Yi is as defined above. Petition 870250075555, dated 08 / 26 / 2025, p. 22 / 279 16 / 177

[0037] In some embodiments, Aci is selected, without limitation, from the group consisting of (D / L)alanine, (D / L)leucine, (D / L)isoleucine, (D / L)valine, (D / L)phenylalanine, (D / L)proline, (D / L)tryptophan, (D / L)serine, (D / L)tyrosine, (D / L)cysteine, (D / L)cystine, (D / L)arginine, (D / L)histidine, (D / L)methionine, (D / L)asparagine, (D / L)glutamine, (D / L)threonine, (D / L)aspartic acid, (D / L)glutamic acid, derivatives of natural or non-natural amino acids and the following structures:

[0038] In some forms, Aci is selected from the following structures: and H OH THE

[0039] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by the formula VIc: Petition 870250075555, dated 08 / 26 / 2025, p. 23 / 279 17 / 177 Formula VIc where Ri, R2, ni, n2 and n3 are as defined above.

[0040] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by the formula VId: where Ri, R2, ni, n2 and n3 are as defined above. Petition 870250075555, dated 08 / 26 / 2025, p. 24 / 279 18 / 177

[0041] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by formula VIe: Formula VIe where Ri, R2, ni, n2 and n3 are as defined above; Ac2 is a hydrophilic structural unit composed of -X2- Y2, and X2 and Y2 are as defined above.

[0042] In some modes, Ac2 is selected, without limitation- tion, of Petition 870250075555, dated 08 / 26 / 2025, page 25 / 279 19 / 177 D ° °Ϋ°0IHo ouHo ; where r is selected from integers between 1 and 10; and e is selected from integers between 1 and 20.

[0043] In some modes, Ac2 is selected from the following HOOC^ structures:οwoh eHo .

[0044] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of the present application, has a structure represented by the formula VIf: Formula VIf where Ri, R2, m, n2 and n3 are as defined above; Aci is a hydrophilic structural unit having the structure shown in the formula d: Petition 870250075555, dated 08 / 26 / 2025, p. 26 / 279 20 / 177 ^'NH The formula for Xi and Yi is as defined above;

[0045] In some embodiments, Aci is selected, without limitation, from the group consisting of (D / L)alanine, (D / L)leucine, (D / L)isoleucine, (D / L)valine, (D / L)phenylalanine, (D / L)proline, (D / L)tryptophan, (D / L)serine, (D / L)tyrosine, (D / L)cysteine, (D / L)cystine, (D / L)arginine, (D / L)histidine, (D / L)methionine, (D / L)asparagine, (D / L)glutamine, (D / L)threonine, (D / L)aspartic acid, (D / L)glutamic acid, derivatives of natural or non-natural amino acids and the following structures: and

[0046] In some forms, Aci is selected from the following structures:

[0047] In some modalities, Aci is: H OH THE

[0048] Ac2 is a hydrophilic structural unit composed of -X2Y2, and the X2 and Y2 are as defined above.

[0049] In some modes, Ac2 is selected, without limitation- tion, from 0 Petition 870250075555, dated 08 / 26 / 2025, p. 27 / 279 21 / 177 D OI OD^Do ouHo ; where r is selected from integers between 1 and 10; and is selected from integers between 1 and 20.

[0050] In some modalities, Ac2 is selected from the following structures: HOOCD „ , , x Ί o । oDkD LJ \ H 11 Hli cooh , o eo .

[0051] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by the formula VIg: VIg formula where Ri, R2, m, n2 and n3 are as defined above; Aci is a hydrophilic structural unit having the structure shown in the formula d: Petition 870250075555, dated 08 / 26 / 2025, p. 28 / 279 22 / 177 The formula for Xi and Yi is as defined above;

[0052] In some embodiments, Aci is selected, without limitation, from the group consisting of (D / L)alanine, (D / L)leucine, (D / L)isoleucine, (D / L)valine, (D / L)phenylalanine, (D / L)proline, (D / L)tryptophan, (D / L)serine, (D / L)tyrosine, (D / L)cysteine, (D / L)cystine, (D / L)arginine, (D / L)histidine, (D / L)methionine, (D / L)asparagine, (D / L)glutamine, (D / L)threonine, (D / L)aspartic acid, (D / L)glutamic acid, derivatives of natural or non-natural amino acids and the following structures: OH and

[0053] In some forms, Aci is selected from the following structures: and H OH THE

[0054] In some modalities, Aci is:

[0055] In some embodiments, the ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof, of the present application, is selected from the following structures: Petition 870250075555, dated 08 / 26 / 2025, p. 29 / 279 23 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 30 / 279 24 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 31 / 279 25 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 32 / 279 26 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 33 / 279 27 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 34 / 279 28 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 35 / 279 29 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 36 / 279 30 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 37 / 279 31 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 38 / 279 32 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 39 / 279 33 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 40 / 279 34 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 41 / 279 35 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 42 / 279 36 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 43 / 279 37 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 44 / 279 38 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 45 / 279 39 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 46 / 279 40 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 47 / 279 41 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 48 / 279 42 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 49 / 279 43 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 50 / 279 44 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 51 / 279 45 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 52 / 279 46 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 53 / 279 47 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 54 / 279 48 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 55 / 279 49 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 56 / 279 50 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 57 / 279 51 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 58 / 279 52 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 59 / 279 53 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 60 / 279 54 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 61 / 279 551177 Petition 870250075555, dated 08 / 26 / 2025, p. 62 / 279 56 / 177 in which chiral carbons in positions 2 and 3 independently have either R or S configuration. In some embodiments, the chiral carbon in Petition 870250075555, dated 08 / 26 / 2025, page 63 / 279 57 / 177 position 2 has an S configuration, and the chiral carbon in position 3 has an S configuration.

[0056] In the present application, the Ab linker unit may be selected from the group consisting of an antibody, an antibody fragment or a protein; the antibody is preferably selected from the group consisting of a murine antibody, a rabbit antibody, a phage display-derived antibody, a yeast display-derived antibody, a chimeric antibody, a humanized antibody, a fully human antibody, an antibody fragment, a bispecific antibody and a multispecific antibody.

[0057] In some embodiments, the antibody is a monoclonal antibody, selected, without limitation, from: anti-EGFRvIII antibody, anti-PD-1 antibody, anti-PD-L1 antibody, anti-DLL-3 antibody, anti-PSMA antibody, anti-CD70 antibody, anti-MUC16 antibody, anti-ENPP3 antibody, anti-TDGF1 antibody, anti-ETBR antibody, anti-MSLN antibody, anti-TIM-1 antibody, anti-LRRC15 antibody, anti-LIV-1 antibody, anti-CanAg / AFP antibody, anti-claudin 18 antibody.2, anti-Mesothelin antibody, anti-HER2(ErbB2) antibody, anti-EGFR antibody, anti-c-MET antibody, anti-SLITRK6 antibody, anti-KIT / CD117 antibody, anti-STEAP1 antibody, anti-SLAMF7 / CS1 antibody, anti-NaPi2B / SLC34A2 antibody, anti-GPNMB antibody, anti-HER3(ErbB3) antibody, anti-MUC1 / CD227 antibody, anti-AXL antibody, anti-CD166 antibody, anti-B7-H3(CD276) antibody, anti-PTK7 / CCK4 antibody, anti-PRLR antibody, anti-EFNA4 antibody, anti-5T4 antibody, anti-NOTCH3 antibody, anti-Nectin 4 antibody, anti-TROP-2 antibody, anti-CD142 antibody, anti-CA6 antibody, antiGPR20 antibody, anti-CD174 antibody, anti-CD71 antibody, anti-EphA2 antibody, anti-LYPD3 antibody, anti-FGFR2 antibody, anti-FGFR3 antibody, anti-FRα antibody, anti-CEACAMs antibody, anti-GCC antibody, anti-Integrin Av antibody, anti-CAIX antibody, anti-P. Petition 870250075555, 08 / 26 / 2025, pág. 64 / 279 58 / 177 cadherin, anti-GD3 antibody, anti-Cadherin 6 antibody, antiLAMP1 antibody, anti-FLT3 antibody, anti-BCMA antibody, anti-CD79b antibody, anti-CD19 antibody, anti-CD33 antibody, anti-CD56 antibody, anti-CD74 antibody, anti-CD22 antibody, anti-CD30 antibody, anti-CD37 antibody, anti-CD47 antibody, anti-CD138 antibody, antibody anti-CD352, anti-CD25 antibody or anti-CD123 antibody.

[0058] In some embodiments, the antibody is an anti-TROP-2 antibody. In some embodiments, the antibody comprises heavy chains and light chains, the light chains comprising CDR-L1, CDR-L2, and CDR-L3 having amino acid sequences established at SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. In some embodiments, the heavy chains comprise CDR-H1, CDR-H2, and CDR-H3, having amino acid sequences established at SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6.

[0059] In some embodiments, the light chain comprises a variable light chain region having an amino acid sequence of SEQ ID NO: 7. In some embodiments, the light chain also comprises a constant light chain region having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the amino acid sequence of the light chain is SEQ ID NO: 9.

[0060] In some embodiments, the light chain comprises a variable light chain region having an amino acid sequence of SEQ ID NO: 10. In some embodiments, the light chain also comprises a constant light chain region having an amino acid sequence of SEQ ID NO: 11. In some embodiments, the amino acid sequence of the light chain is SEQ ID NO: 12.

[0061] In some embodiments, the heavy chain comprises a variable heavy chain region having an amino acid sequence of SEQ ID NO: 13. In some embodiments, the heavy chain also comprises a constant heavy chain region having Petition 870250075555, dated 08 / 26 / 2025, p. 65 / 279 59 / 177 of an amino acid sequence of SEQ ID NO: 14. In some embodiments, the amino acid sequence of a heavy chain is SEQ ID NO: 15.

[0062] In some embodiments, the antibody is an anti-TROP-2 antibody. In some embodiments, the antibody comprises heavy chains and light chains, the light chains comprising CDR-L1, CDR-L2, and CDR-L3 having nucleic acid coding sequences established at SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18. In some embodiments, the heavy chains comprise CDRH1, CDR-H2, and CDR-H3 having nucleic acid coding sequences established at SEQ ID NO: 19, SEQ ID NO: 20, and SEQ ID NO: 21.

[0063] In some embodiments, the light chain comprises a variable light chain region having a nucleic acid coding sequence of SEQ ID NO: 22. In some embodiments, the light chain also comprises a constant light chain region having a nucleic acid coding sequence of SEQ ID NO: 23. In some embodiments, the nucleic acid coding sequence of the light chain is SEQ ID NO: 24.

[0064] In some embodiments, the light chain comprises a variable light chain region having a nucleic acid coding sequence of SEQ ID NO: 25. In some embodiments, the light chain also comprises a constant light chain region having a nucleic acid coding sequence of SEQ ID NO: 26. In some embodiments, the nucleic acid coding sequence of the light chain is SEQ ID NO: 27.

[0065] In some embodiments, the heavy chain comprises a variable heavy chain region having a nucleic acid coding sequence of SEQ ID NO: 28. In some embodiments, the heavy chain also comprises a constant chain region. Petition 870250075555, dated 08 / 26 / 2025, page 66 / 279 60 / 177 heavy chain having a nucleic acid coding sequence of SEQ ID NO: 29. In some embodiments, the nucleic acid coding sequence of a heavy chain is SEQ ID NO: 30.

[0066] Partial sequence information involved in the present invention is provided in Table 1. Table 1: Description of the sequences SEQ ID NO: Description Sequences 1 CDR-L1 amino acid sequence RASQDINKYLA 2 CDR-L2 amino acid sequence STSTLQS 3 CDR-L3 amino acid sequence LQYDDLFT 4 CDR-H1 amino acid sequence SFDIN 5 CDR-H2 amino acid sequence WIFPGDGNTKYSQKFQG 6 CDR-H3 amino acid sequence GEALYYFDY 7 TR001 light chain variable region amino acid sequence DIQMTQSPSSLSASVGDRVTITC RASQDINKYLAWYQQKPGKVPK LLIYSTSTLQSGVPSRFSGSGSG TDFTLTISSLQPEDVATYYCLQY DDLFTFGQGTKLEIK 8 TR001 light chain constant region amino acid sequence RTVAAPSVFIFPPSDEQLKSGTA SVVCLLNN FYPREAKVQWKVD N ALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVT HQGLSSPVTKSFNRGEC Petition 870250075555, dated 08 / 26 / 2025, p. 67 / 279 61 / 177 SEQ ID NO: Description Sequences 9 Amino acid sequence of the light chain of TR001 DIQMTQSPSSLSASVGDRVTITC RASQDINKYLAWYQQKPGKVPK LLIYSTSTLQSGVPSRFSGSGSG TDFTLTISSLQPEDVATYYCLQY DDLFTFGQGTKLEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLS KADYEKH KVYAC EVTHQG LSSP VTKSFNRGEC 10 Amino acid sequence of the variable region of the light chain of TR002 DIQMTQSPSSLSASVGDRVTITC RASQDINKYLAWYQQKPGKVPK LLIYSTSTLQSGVPSRFSGSGSG TDFTLTISSLQPEDVATYYCLQY DDLFTFGQGTKLEIK 11 Amino acid sequence of the constant region of the light chain of TR002 RTVAAPSVFIFPPSDEQLKSGTA SVVCLLNN FYPREAKVQWKVD N ALQSGNSQESVTEQDSKDSTYS LSSTLTLSKADYEKHKVYACEVT HQGLSSPVCTKSFNRGEC 12 Amino acid sequence of the light chain of TR002 DIQMTQSPSSLSASVGDRVTITC RASQDINKYLAWYQQKPGKVPK LLIYSTSTLQSGVPSRFSGSGSG TDFTLTISSLQPEDVATYYCLQY DDLFTFGQGTKLEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLS Petition 870250075555, dated 08 / 26 / 2025, page 68 / 279 62 / 177 SEQ ID NO: Description Sequences KADYEKHKVYACEVTHQGLSSP VCTKSFNRGEC 13 Amino acid sequences from a variable heavy chain region of TR001 and TR002 QVQLVQSGAEVKKPGASVKLSC KASGYTFTSFDINWVRQAPEQR LEWMGWIFPGDGNTKYSQKFQ GRATITRDTSASTAYMELSSLRS EDTAVYYCVRGEALYYFDYWG QGTLVTVSS 14 Amino acid sequences from a constant heavy chain region of TR001 and TR002 ASTKGPSVFPLAPSSKSTSGGT AALGCLVKDYFPEPVTVSWNSG ALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGTQTYICNVNHKPS NTKVDKRVEPKSCDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKE YKCKVSNKALPAPIEKTISKAKG QPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPG 15 Amino acid sequences of a heavy chain of TR001 and TR002 QVQLVQSGAEVKKPGASVKLSC KASGYTFTSFDINWVRQAPEQR LEWMGWIFPGDGNTKYSQKFQ GRATITRDTSASTAYMELSSLRS EDTAVYYCVRGEALYYFDYWG Petition 870250075555, dated 08 / 26 / 2025, page 69 / 279 63 / 177 SEQ ID NO: Description Sequences QGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKRVEPKS CDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVV DVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLP PSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQK SLSLSPG 16 CDR-L1 nucleic acid coding sequence AGAGCTTCTCAGGATATCAATA AGTATCTGGCT 17 Nucleic acid coding sequence of CDR-L2 TCTACATCTACCCTGCAGTCT 18 Nucleic acid coding sequence of CDRL3 CTGCAGTATGATGATCTGTTCA CC 19 Nucleic acid coding sequence of CDR-H1 TCCTTCGACATTAAC Petition 870250075555, dated 08 / 26 / 2025, page 70 / 279 64 / 177 SEQ ID NO: Description Sequences 20 Nucleic acid coding sequence of CDR-H2 TGGATCTTCCCCGGCGACGGC AACACCAAGTACTCCCAGAAGT TCCAGGGA 21 Nucleic acid coding sequence of CDR-H3 GGAGAGGCTCTGTACTAIIIIG ATTAT 22 Nucleic acid coding sequence of the variable region of the TR001 light chain GATATCCAGATGACCCAGTCTC CATCTAGCCTGTCCGCTTCTGT GGGCGATAGAGTGACCATCAC ATGCAGAGCTTCTCAGGATATC AATAAGTATCTGGCTTGGTATC AGCAGAAGCCTGGAAAGGTGC CTAAGCTGCTGATCTACTCTAC ATCTACCCTGCAGTCTGGAGT GCCTTCTAGAIIII CTGGATCT GGCTCTGGCACCGAI II IACA CTGACAATCTCπCCTTGCAGC CTGAGGATGTGGCTACATATTA TTGTCTGCAGTATGATGATCTG IICACC III GGCCAGGGCACC AAGCIGGAGAICAAG 23 Nucleic acid coding sequence of the TR001 light chain constant region CGTACGGTGGCTGCACCATCT GTCπCATCπCCCGCCATCTG ATGAGCAGπGAAATCTGGAAC TGCCTCTGπGTGTGCCTGCT GAATAACTTCTATCCCAGAGAG GCCAAAGIACAGIGGAAGGIG GATAACGCCCTCCAATCGGGT Petition 870250075555, dated 08 / 26 / 2025, p. 71 / 279 65 / 177 SEQ ID NO: Description Sequences AACTCCCAGGAGAGTGTCACA GAGCAGGACAGCAAGGACAGC ACCTACAGCCTCAGCAGCACC CTGACGCTGAGCAAAGCAGAC TACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGG GCCTGAGCTCGCCCGTCACAA AGAGCTTCAACAGGGGAGAGT GTTAG 24 Light chain nucleic acid coding sequence of TR001 GATATCCAGATGACCCAGTCTC CATCTAGCCTGTCCGCTTCTGT GGGCGATAGAGTGACCATCAC ATGCAGAGCTTCTCAGGATATC AATAAGTATCTGGCTTGGTATC AGCAGAAGCCTGGAAAGGTGC CTAAGCTGCTGATCTACTCTAC ATCTACCCTGCAGTCTGGAGT GCCTTCTAGA Illi CTGGATCT GGCTCTGGCACCGAT TT TACA CTGACAATCTCTTCTCTGCAGC CTGAGGATGTGGCTACATATTA TTGTCTGCAGTATGATGATCTG TTCACC TTT GGCCAGGGCACC AAGCTGGAGATCAAGCGTACG GTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCA GTTGAAATCTGGAACTGCCTCT GTTGTGTGCCTGCTGAATAACT Petition 870250075555, dated 08 / 26 / 2025, p. 72 / 279 66 / 177 SEQ ID NO: Description Sequences TCTATCCCAGAGAGGCCAAAG TACAGTGGAAGGTGGATAACG CCCTCCAATCGGGTAACTCCC AGGAGAGTGTCACAGAGCAGG ACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGC TGAGCAAAGCAGACTACGAGA AACACAAAGTCTACGCCTGCG AAGTCACCCATCAGGGCCTGA GCTCGCCCGTCACAAAGAGCT TCAACAGGGGAGAGTGTTAG 25 Nucleic acid coding sequence of the variable light chain region of TR002 GATATCCAGATGACCCAGTCTC CATCTAGCCTGTCCGCTTCTGT GGGCGATAGAGTGACCATCAC ATGCAGAGCTTCTCAGGATATC AATAAGTATCTGGCTTGGTATC AGCAGAAGCCTGGAAAGGTGC CTAAGCTGCTGATCTACTCTAC ATCTACCCTGCAGTCTGGAGT GCCTTCTAGA Illi CTGGATCT GGCTCTGGCACCGAI II IACA CTGACAATCTCTTCTCTGCAGC CTGAGGATGTGGCTACATATTA TTGTCTGCAGTATGATGATCTG IICACC III GGCCAGGGCACC AAGCIGGAGAICAAG Petition 870250075555, dated 08 / 26 / 2025, p. 73 / 279 67 / 177 SEQ ID NO: Description TR002 light chain constant sequences ATGAGCAGTTGAAATCTGGAAC TGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAG GCCAAAGTACAGTGGAAGGTG GATAACGCCCTCCAATCGGGT AACTCCCAGGAGAGTGTCACA GAGCAGGACAGCAAGGACAGC ACCTACAGCCTCAGCAGCACC CTGACGCTGAGCAAAGCAGAC TACGAGAAACACAAAGTCTACG CCTGCGAAGTCACCCATCAGG GCCTGAGCTCGCCCGTCTGTA CAAAGAGCTTCAACAGGGGAG AGTGTTAG 27 Nucleic acid coding sequence of the TR002 light chain GATATCCAGATGACCCAGTCTC CATCTAGCCTGTCCGCTTCTGT GGGCGATAGAGTGACCATCAC ATGCAGAGCTTCTCAGGATATC AATAAGTATCTGGCTTGGTATC AGCAGAAGCCTGGAAAGGTGC CTAAGCTGCTGATCTACTCTAC ATCTACCCTGCAGTCTGGAGT GCCTTCTAGA Illi CTGGATCT GGCTCTGGCACCGAT TT TACA CTGACAATCTCTTCTCTGCAGC CTGAGGATGTGGCTACATATTA TTGTCTGCAGTATGATGATCTG TTCACC TTT GGCCAGGGCACC Petition 870250075555, dated 08 / 26 / 2025, p. 74 / 279 68 / 177 SEQ ID NO: Description Sequences AAGCTGGAGATCAAGCGTACG GTGGCTGCACCATCTGTCTTCA TCTTCCCGCCATCTGATGAGCA GTTGAAATCTGGAACTGCCTCT GTTGTGTGCCTGCTGAATAACT TCTATCCCAGAGAGGCCAAAG TACAGTGGAAGGTGGATAACG CCCTCCAATCGGGTAACTCCC AGGAGAGTGTCACAGAGCAGG ACAGCAAGGACAGCACCTACA GCCTCAGCAGCACCCTGACGC TGAGCAAAGCAGACTACGAGA AACACAAAGTCTACGCCTGCG AAGTCACCCATCAGGGCCTGA GCTCGCCCGTCTGTACAAAGA GCTTCAACAGGGGAGAGTGTT AG 28 Nucleic acid coding sequences of a variable heavy chain region of TR001 and TR002 CAGGTGCAGCTGGTGCAGTCC GGCGCCGAGGTGAAGAAGCC CGGCGCCTCCGTGAAGCTGAG CTGTAAGGCCTCCGGCTACAC CTTCACCTCCTTCGACATTAAC TGGGTGCGGCAGGCCCCGA GCAGCGCCTGGAGTGGATGG GCTGGATCTTCCCCGGCGACG GCAACACCAAGTACTCCCAGA AGTTCCAGGGAAGAGCTACCA TCACCAGAGATACATCCGCTTC Petition 870250075555, dated 08 / 26 / 2025, page 75 / 279 69 / 177 SEQ ID NO: Description Sequences TACAGCTTACATGGAGCTGTCT AGCCTGAGATCTGAGGATACA GCTGTGTATTACTGTGTGAGAG GAGAGGCTCTGTACTAIIIIGA TTATTGGGGCCAGGGCACCCT GGTGACAGTGTCTTCT 29 Nucleic acid coding sequences of a constant heavy chain region of TR001 and TR002 GCTAGCACCAAGGGCCCATCG GTCTTCCCCCTGGCACCCTCC TCCAAGAGCACCTCTGGGGGC ACAGCGGCCCTGGGCTGCCTG GTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAAC TCAGGCGCCCTGACCAGCGGC GTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACT CCCTCAGCAGCGTGGTGACCG TGCCCTCCAGCAGCTTGGGCA CCCAGACCTACATCTGCAACG TGAATCACAAGCCCAGCAACA CCAAGGTGGACAAGAGAGTTG AGCCCAAATCTTGTGACAAAAC TCACACATGCCCACCGTGCCC AGCACCTGAACTCCTGGGGG ACCGTCAGTCTTCCTCTTCCCC CCAAAACCCAAGGACACCCTC ATGATCTCCGGACCCCTGAG GTCACATGCGTGGTGGTGGAC GTGAGCCACGAAGACCCTGAG Petition 870250075555, dated 08 / 26 / 2025, page 76 / 279 70 / 177 SEQ ID NO: Description Sequences GTCAAGTTCAACTGGTACGTG GACGGCGTGGAGGTGCATAAT GCCAAGACAAAGCCGCGGGAG GAGCAGTACAACAGCACGTAC CGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTG AATGGCAAGGAGTACAAGTGC AAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACC ATCTCCAAAGCCAAAGGGCAG CCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGAT GAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAA GGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAAT GGGCAGCCGGAGAACAACTAC AAGACCAGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTC CTCTATAGCAAGCTCACCGTG GACAAGAGCAGGTGGCAGCAG GGGAACGTCTTCTCATGCTCC GTGATGCATGAGGCTCTGCAC AACCACTACACGCGAAGAGC CTCTCCCTGTCTCCGGGTTAA 30 Nucleic acid coding sequences of a heavy chain of TR001 CAGGTGCAGCTGTGCAGTCC GGCGCCGAGGTGAAGAAGCC CGGCGCCTCCGTGAAGCTGAG Petition 870250075555, dated 08 / 26 / 2025, page 77 / 279 71 / 177 SEQ ID NO: Description Sequences and TR002 CTGTAAGGCCTCCGGCTACAC CTTCACCTCCTTCGACATTAAC TGGGTGCGGCAGGCCCCCGA GCAGCGCCTGGAGTGGATGG GCTGGATCTTCCCCGGCGACG GCAACACCAAGTACTCCCAGA AGTTCCAGCCAGCCAGCCAGCCAGTCCAGA TACAGCTTACATGGAGCTGTCT AGCCTGAGATCTGAGGATACA GCTGTGTATTACTGTGTGAGAG GAGAGGCTCTGTACTAIIIIGA TTATTGGGGCCAGGGCACCCT GGTGACAGTGTCTTCTGCTAG CACCAAGGGCCCATCGGTCTT CCCCCTGGCACCCTCCCTCGACCGCCGCCTT GGCCCTGGGCTGCCTGGTCAA GGACTACTTCCCCGAACCGGT GACGGTGTCGTGGAACTCAGG CGCCCTGACCAGCGGCGTGCA CACCTTCCCGGCTGTCCTACA GTCCTCAGGACTCTACTCCCTC AGCAGCGTGGTGACCGTGCCC TCCAGCAGCTTGGCACCAG ACCTACCATGACCGCA ACAAGCCCAGCAACACCAAGG TGGACAAGAGAGTTGAGCCCA Petition 870250075555, of 26 / 08 / 2025, p. 78 / 279 72 / 177 SEQ ID NO: Description Sequences AATCTTGTGACAAAACTCACAC ATGCCCACCGTGCCCAGCACC TGAACTCCTGGGGGGACCGTC AGTCTTCCTCTTCCCCCCAAAA CCCAAGGACACCTCATGATC TCCCGGACCCTGAGGTCACA TTCAACTGGTACGTGGACGGC GTGGAGGTGCATAATGCCAAG ACAAAGCCGCGGGAGGAGCA GTACAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCT GCACCAGGACTGGCTGAATGG CAAGGAGTACAAGTGCAAGGT CTCCAACAAAGCCCTCCCAGACCACCAGACCAGCCAGCCAGCCAGCCAGCAGCC AGAACCACAGGTGTACACCCT GCCCCCATCCCGGGATGAGCT GACCAAGAACCAGGTCAGCCT GACCTGCCTGGTCAAAGGCTT CTATCCCAGCGACATCGCCGT GGAGTGGGAGAGCAATGGGCA GCCGGAGAACAACTACAAGAC CACGCCTCCCGTGCTGGACTCCTTCCTTCCTT AGCAAGCTCACCGTGGACAAG Petition 870250075555, of 26 / 08 / 2025, p. 79 / 279 73 / 177 SEQ ID NO: Description Sequences AGCAGGTGGCAGCAGGGGAA CGTCTTCTCATGCTCCGTGATG CATGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCC CTGTCTCCGGGTTAA

[0067] In a second aspect, the present application provides a drug-ligand conjugate of formula VIII or formula IX, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof, in which, Mi is a ligand unit, Z, p, A, G, W, Ri, R2 and R3 are as defined above.

[0068] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or the Petition 870250075555, dated 08 / 26 / 2025, p. 80 / 279 74 / 177 mixture thereof, or the pharmaceutically acceptable solvate or salt thereof, of this application, has a structure represented by formula VIII-1 or formula IX-1, where Z, A, Ri, R2, R3, R5, R6 and R7 are as defined above.

[0069] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof, of the present application, has a structure represented by formula VIIIa or formula Ka: Formula VIIIa Petition 870250075555, dated 08 / 26 / 2025, p. 81 / 279 75 / 177 Formula IXa, in which R1, R2, and R3 are as defined above.

[0070] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, has a structure represented by formula VIIb or formula IXb: Formula VIIIb Formula IXb where Ac is a hydrophilic structural unit having the structure shown in formula d: 'NH Formula d Petition 870250075555, dated 08 / 26 / 2025, p. 82 / 279 76 / 177 X and Y are as defined above. In some embodiments, Ac is as defined above.

[0071] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, has a structure represented by formula VIIIc: VIIIc where Ri and R2 are as defined above.

[0072] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, has a structure represented by formula VIIId: where R1 and R2 are as defined above.

[0073] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, has a structure represented by Petition 870250075555, dated 08 / 26 / 2025, page 83 / 279 77 / 177 formula VIIe: Formula VIIe wherein, R1 and R2 are as defined above; AC2 is a hydrophilic structural unit composed of -X2-Y2, and AC2, X2 and Y2 are as defined above.

[0074] In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, has a structure represented by the formula Vlllf: Formula VIIIf where Ri and R2 are as defined above; Aci is a hydrophilic structural unit composed of -XiYi, and Xi and Yi are as defined above.

[0075] In some embodiments, Aci is selected, without limitation, from the group consisting of (D / L) alanine, (D / L) leucine, (D / L) isoleucine, (D / L) valine, (D / L) phenylalanine, (D / L) proline, (D / L) tryptophan, (D / L) serine, (D / L) tyrosine, (D / L) cysteine, (D / L) cystine, (D / L) arginine, (D / L) histidine, (D / L) methionine, (D / L) asparagine, (D / L) glutamine, Petition 870250075555, dated 08 / 26 / 2025, p. 84 / 279 78 / 177 (D / L) threonine, (D / L) aspartic acid, (D / L) glutamic acid, derived from natural or non-natural amino acids and the following structures: and

[0076] In some modalities, Aci is selected from the following

[0077] structures: and In some modalities, Aci is:

[0078] Ac2 is a hydrophilic structural unit composed of -X2Y2, and Ac2, X2 and Y2 are as defined above.

[0079] In some embodiments, the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, has a structure represented by the formula VlIIg: Formula VlIIg where Ri and R2 are as defined above;

[0080] Aci is a hydrophilic structural unit composed of -XiYi, and Xi and Yi are as defined above.

[0081] In some modalities, the Aci is selected, without limitation. Petition 870250075555, dated 08 / 26 / 2025, page 85 / 279 79 / 177 tion, from the group consisting of (D / L) alanine, (D / L) leucine, (D / L) isoleucine, (D / L) valine, (D / L) phenylalanine, (D / L) proline, (D / L) tryptophan, (D / L) serine, (D / L) tyrosine, (D / L) cysteine, (D / L) cystine, (D / L) arginine, (D / L) histidine, (D / L) methionine, (D / L) asparagine, (D / L) glutamine, (D / L) threonine, (D / L) aspartic acid, (D / L) glutamic acid, derivatives of natural or unnatural amino acids and the following structures: and

[0082] In some forms, Aci is selected from the following structures: and o.> ô X OHNΠ

[0083] In some embodiments, Aci is:Ho . In some embodiments, the ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, is selected from the following structures: Petition 870250075555, dated 08 / 26 / 2025, p. 86 / 279 80 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 87 / 279 81 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 88 / 279 82 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 89 / 279 83 / 177 Petition 870250075555, dated 08 / 26 / 2025, pp. 90 / 279 84 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 91 / 279 85 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 92 / 279 86 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 93 / 279 87 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 94 / 279 88 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 95 / 279 89 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 96 / 279 90 / 177 Petition 870250075555, dated 08 / 26 / 2025, p. 97 / 279 91 / 177 in which chiral carbons in positions 2 and 3 independently have either R or S configuration. In some embodiments, the chiral carbon in position 2 has S configuration, and the chiral carbon in position 3 has S configuration. Petition 870250075555, dated 08 / 26 / 2025, pp. 98 / 279 92 / 177 configuration S.

[0084] In a third aspect, the present application provides a compound of formula X, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof, Formula X where W is an oxygen atom or a sulfur atom, and preferably, W is an oxygen atom; Ri and Rs are each independently selected from the group consisting of: hydrogen atom, alkyl, acyl, sulfonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, and are not simultaneously hydrogen; optionally, the alkyl, acyl, sulfonyl, cycloalkyl, aryl and heteroaryl are each independently substituted by one or more substituents selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxy, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; preferably, Ri is alkyl, and Rs is H; R2 is -C(O)-Qi-Q2 or -SO2-Q1-Q2, where Qi is selected from the group consisting of O, N, and S atoms and a chemical bond; In a case where Qi is selected from the group consisting of O, N, and S atoms, Q2 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl, and heteroaryl, and optionally alkyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl, and heteroaryl are each Petition 870250075555, dated 08 / 26 / 2025, pp. 99 / 279 93 / 177 which independently substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxy, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl atoms; In a case where Qi is a chemical bond, Q2 is selected from the group consisting of alkyl, benzyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl, and heteroaryl; In a case where Q2 is an alkyl group, the alkyl group is replaced by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, cyano, azido, nitro, carboxyl, acyl, carbonyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms; In a case where Q2 is selected from the group consisting of cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl, and heteroaryl, the cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl, and heteroaryl are each independently substituted by one or more substituents selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, and in a case where Q2 is the cycloalkyl with the substituent being a hydroxyl, an amino, or a mercapto, the substituent is in any position except a carbon atom connected to -C(O)-.

[0085] In some embodiments, the compound of formula X, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof, is a compound of formula XIa or formula XIb, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, Petition 870250075555, dated 08 / 26 / 2025, pp. 100 / 279 94 / 177 Formula XIa The formula Xlb where: Ri is an alkyl group, and preferably Ri is a methyl group. Qi is an O atom or a chemical bond; In a case where Qi is an O atom, Q2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl and aryl, and optionally the alkyl, cycloalkyl, alkenyl and aryl are each independently substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, hydroxyalkyl and aryl atoms; In a case where Qi is a chemical bond, Q2 is selected from the group consisting of alkyl, benzyl, cycloalkyl, alkenyl, and aryl; In a case where Q2 is an alkyl group, the alkyl group is replaced by one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, deuterium, azide, nitro, and aryl atoms; In a case where Q2 is selected from the group consisting of cycloalkyl, alkenyl, and aryl, the cycloalkyl, alkenyl, and aryl groups are each independently substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxyl, hydroxyalkyl, and aryl atoms; and in a case where Q2 is a cycloalkyl group with the substituent being a hydroxyl, an amino, or a mercapto group, the substituent is in any position except a carbon atom connected to -C(O)-.

[0086] In some embodiments, the compound of formula X, or the Petition 870250075555, dated 08 / 26 / 2025, pp. 101 / 279 95 / 177 isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof, of the present application, is selected from the following structures: Petition 870250075555, dated 08 / 26 / 2025, page 102 / 279 96 / 177

[0087] In some embodiments of the present application, pharmaceutically acceptable salts of the drug-ligand conjugate, or the drug-ligand conjugate or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, or the compound of formula X or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, include sodium, potassium, calcium or magnesium salts formed by acidic functional groups in the structural formula and acetates, trifluoroacetates, citrates, oxalates, tartrates, malates, nitrates, chlorides, bromides, iodides, sulfates, bisulfates, phosphates, lactates, oleates, ascorbates, salicylates, formates, glutamates, methanes Petition 870250075555, dated 08 / 26 / 2025, page 103 / 279 97 / 177 sulfonates, ethanesulfonates, benzenesulfonates or ptoluenesulfonates formed by basic functional groups in the structure.

[0088] In a fourth aspect, the present application provides use of the drug-ligand conjugate or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to any of the solutions described above, or the compound of formula X or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to any of the solutions described above as an intermediate for the preparation of the drug-ligand conjugate of the present application.

[0089] In a fifth aspect, the present application provides a pharmaceutical composition comprising the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof of the present application, or the drug-ligand conjugate or the isomer, mesomer, racemate, enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, or the compound of formula X or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof, and optionally further comprising a pharmaceutically acceptable carrier.

[0090] In a sixth aspect, the present application provides a pharmaceutical formulation comprising the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof of the present application, or the drug-ligand conjugate or the isomer, mesomer, racemate, enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, or the compound of formula X or the isomer, mesomer, racemate Petition 870250075555, dated 08 / 26 / 2025, p. 104 / 279 98 / 177 or an enantiomer thereof or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof.

[0091] In a seventh aspect, the present application provides use of the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof according to any of the solutions described above, or the drug-ligand conjugate or the isomer, mesomer, racemate, enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to any of the solutions described above, or the compound of formula X or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to any of the solutions described above in the preparation of a medicament for the treatment or prevention of a cancer or tumor.

[0092] In an eighth aspect, the present application provides a method of preventing or treating a cancer or tumor, comprising administering to a subject in need thereof a prophylactic or therapeutically effective amount of the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof of the present application, or the drug-ligand conjugate or the isomer, mesomer, racemate, enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof of the present application, or the compound of formula X or the isomer, mesomer, racemate or enantiomer thereof or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof.

[0093] In the present application, cancer or tumor may be a solid tumor or a hematologic tumor, including but not limited to: adenocarcinoma, ovarian cancer, cervical cancer, uterine cancer, prostate cancer, renal cancer, urinary tract cancer, bladder cancer, liver cancer, stomach cancer, endometrial cancer, cancer of Petition 870250075555, dated 08 / 26 / 2025, page 105 / 279 99 / 177 salivary gland, esophageal cancer, lung cancer (e.g., lung adenocarcinoma), colon cancer, rectal cancer, colorectal cancer, bone cancer, skin cancer (e.g., epidermal cancer), thyroid cancer, pancreatic cancer (e.g., pancreatic adenocarcinoma), melanoma, glioma, neuroblastoma, glioblastoma multiforme, sarcoma, lymphoma, leukemia, and hypopharyngeal cancer (e.g., hypopharyngeal squamous cell carcinoma). Definitions

[0094] Unless otherwise defined, all technical and scientific terms used herein are consistent with the common understanding of those with common knowledge in the field to which the invention pertains. Although any methods and materials similar or equivalent to those described herein may be used to practice or test the invention, the invention describes preferred methods and materials. In describing and claiming the invention, the following terms are used in accordance with the definitions below.

[0095] When a trade name is used herein, the Applicants intend to include formulations of a product of the trade name, generic drugs and active portions of the trade name.

[0096] Unless otherwise indicated, the terms used in the descriptive report and claims have the following meanings.

[0097] The term ligand refers to a targeting agent that binds specifically to a target portion. The ligand is capable of specifically binding to a cellular component or other target molecules of interest. The targeting portion or target is usually on the cell surface. In some respects, the ligand functions to deliver the drug unit to a specific target cell population with which the ligand unit interacts. Ligands include, but are not limited to, proteins, polypeptides, and peptides, as well as non-proteins such as sugars. Suitable ligand units include, for example, Petition 870250075555, dated 08 / 26 / 2025, page 106 / 279 100 / 177 For example, antibodies, such as full-length (intact) antibodies and antigen-binding fragments. In embodiments where the ligand unit is a non-antibody targeting agent, it may be a peptide or polypeptide, or a non-protein molecule. Examples of such targeting agents include interferons, lymphokines, hormones, growth factors and colony-stimulating factors, vitamins, nutrient transport molecules, or any other cell-binding molecules or substances. In some embodiments, the ligand is covalently connected to the sulfur atom of the ligand. In some aspects, the sulfur atom is that of a cysteine ​​residue that forms an interchain disulfide bond of the antibody. In another aspect, the sulfur atom is a sulfur atom that has been introduced into a cysteine ​​residue of a ligand unit, which forms an interchain disulfide bond of the antibody.In another aspect, the sulfur atom is a sulfur atom from a cysteine ​​residue introduced into a ligand unit, for example, by directed mutagenesis or chemical reaction.

[0098] The term drug refers to a cytotoxic drug, that is, a molecule that has a strong ability to destroy the normal growth of tumor or cancerous cells. In principle, cytotoxic drugs can kill tumor cells at sufficiently high concentrations, but due to a lack of specificity, while killing tumor or cancerous cells, they can also cause apoptosis of normal cells, easily leading to serious side effects.

[0099] The term ligand-drug conjugate refers to a molecule formed by connecting a ligand to a drug via a stable binding unit. In the present invention, the ligand-drug conjugate is preferably an antibody-drug conjugate (ADC), which refers to the connection of a monoclonal antibody or a Petition 870250075555, dated 08 / 26 / 2025, p. 107 / 279 101 / 177 functional antibody fragment or a target protein to a cytotoxic drug via a stable binding unit.

[00100] The term antibody or functional antibody fragment includes, within its scope, any part of the structure of an antibody. This unit can bind, reactively associate with, or complex a receptor, antigen, or other receptor unit present in the target cell population. The antibody can be any protein or protein molecule that binds, complexes, or reacts with a portion of the cell population to be treated or biomodified.

[00101] The antibodies of the present invention include, but are not limited to, mouse antibodies, chimeric antibodies, humanized antibodies and fully human antibodies, preferably humanized antibodies and fully human antibodies.

[00102] The three-letter and single-letter codes for amino acids J. boil. Chem. 1968, 243, 3558.

[00103] The term natural amino acid refers to amino acids that can be synthesized by organisms. Natural amino acids are generally of the L type, but there are some exceptions, such as glycine, including both natural and biosynthesized glycine.

[00104] The term non-natural amino acid refers to amino acids that can only be synthesized artificially.

[00105] The term alkyl refers to a lyphatic hydrocarbon group, which is a linear or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl containing 1 to 12 carbon atoms, more preferably an alkyl containing 1 to 10 carbon atoms, most preferably an alkyl containing 1 to 6 or 1 to 4 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2 Petition 870250075555, dated 08 / 26 / 2025, p. 108 / 279 102 / 177 trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched isomers thereof.More preferably, the alkyl group is a lower alkyl having 1 to 6 (e.g., 1 to 4) carbon atoms, and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl and the like. Alkyl groups can be substituted or unsubstituted. When substituted, substituent groups can be substituted at any available point of connection.The substituent group(s) is / are preferably one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, and oxo.

[00106] The term substituted alkyl means that the hydrogen in an alkyl group is replaced by a substituent. Unless otherwise specified in the text, the substituent of the alkyl group may be one or more groups selected from the group consisting of: -halogen, -OR', -NR'R'', -SR', -SiR'R”R'”, -OC(O)R', -C(O)R', -CO2R', -CONR'R'', Petition 870250075555, dated 08 / 26 / 2025, pp. 109 / 279 103 / 177 OC(O)NR'R'', -NR''C(O)R', -NR'-C(O)NR' 'R''', -NR''C(O)2R', -NHC(NH2)=NH, -NR'C(NH2)=NH, -NH-C(NH2)=NR', -S(O)R', -S(O)2R', S(O)2NR'R'', -NR'S(O)2R'', -CN and -NO2, the number of substituents is 1 to (2m'+1), where m' is the total number of carbon atoms in the group, such as 1, 2, 3, 4, 5 or 6. R', R'' and R''' respectively refer to hydrogen, C1-8 alkyl, aryl, aryl substituted with 1 to 3 halogens, C1-8 alkyl substituted with 1 to 3 halogens, C1-8 alkoxy or C1-8 thioalkoxy, or unsubstituted C1-4 aryl alkyl. When R' and R'' are connected to the same nitrogen atom, they can form a 3-, 4-, 5-, 6-, or 7-membered ring along with the nitrogen atom. For example, NR'R'' includes 1-pyrrolidinyl and 4-morpholinyl.

[00107] The term heteroalkyl refers to a group formed by replacing one or more carbon atoms in an alkyl group with N, O, or S. The heteroalkyl preferably contains 1 to 12 carbon atoms, more preferably 1 to 10 carbon atoms, and most preferably 1 to 6 or 1 to 4 carbon atoms.

[00108] The term cycloalkyl refers to a hydrocarbon group in the form of a saturated or partially unsaturated monocyclic or polycyclic ring, and the ring of a cycloalkyl contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, more preferably 3 to 10 carbon atoms, and most preferably 3 to 8 carbon atoms. Non-limiting examples of monocyclic cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, and cyclooctyl. Non-limiting examples of polycyclic cycloalkyl include spiro, fused, and bridging cycloalkyl groups, and each of the spiro, fused, and bridging groups preferably contains 5 to 12 atoms in the ring. Optionally, one or more carbon atoms in a cycloalkyl group can be replaced by one or more carbonyl groups.

[00109] The term alkoxy refers to an -O-(alkyl) group and an -O- Petition 870250075555, dated 08 / 26 / 2025, p. 110 / 279 104 / 177 (cycloalkyl), where alkyl and cycloalkyl are as defined above. The alkyl preferably contains 1 to 12 carbon atoms, more preferably 1 to 10 carbon atoms, most preferably 1 to 6 or 1 to 4 carbon atoms; the cycloalkyl contains 3 to 20 carbon atoms, preferably 3 to 12 carbon atoms, most preferably 3 to 10 carbon atoms, most preferably 3 to 8 carbon atoms. Non-limiting examples of alkoxy include: methoxy, ethoxy, propoxy, butoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, and cyclohexyloxy. The alkoxy may be optionally substituted or unsubstituted.When substituted, the substituent group(s) is / are preferably one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, thiol, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, and heterocycloalkylthio.

[00110] The term heterocycle refers to a saturated or partially unsaturated monocyclic or polycyclic ring-shaped hydrocarbon containing 3 to 20 ring atoms, of which one or more (such as 1, 2, 3, or 4) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)m (where m is 0, 1, or 2), and the remaining ring atoms are carbon. Preferably, the heterocyclyl contains 3 to 12 ring atoms, of which 1 to 4 are heteroatoms. More preferably, the heterocyclyl contains 3 to 10 or 3 to 8 ring atoms. Non-limiting examples of monocyclic heterocyclyls include pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, and homopiperazinyl. Non-limiting examples of polycyclic heterocyclides include spiro, fused, and bridging heterocyclides, each of which preferably contains 5 to 12 ring atoms. Optionally, one or more carbon atoms in a heterocyclide may be replaced by one or more carbonyl groups. Petition 870250075555, dated 08 / 26 / 2025, p. 111 / 279 105 / 177

[00111] The term aryl refers to a fused monocyclic or polycyclic carbon group of 6 to 14 members (i.e., rings sharing adjacent pairs of carbon atoms) having a conjugated π electron system, preferably a group of 6 to 10 members, such as phenyl. The aryl group may be substituted or unsubstituted. When the aryl group is substituted, the substituent may be one or more of the following groups, selected from, but not limited to, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, deuterium atom, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkyloxy, heterocycloalkyloxy, cycloalkylthio, and heterocycloalkylthio.

[00112] The term heteroaryl includes monocyclic heteroaryls with 5 to 8 members and fused heteroaryls with 8 to 12 members.

[00113] The term 5- to 8-membered monocyclic heteroaryl refers to an aromatic monocyclic ring group containing 5 to 8 ring atoms (at least one of which is a heteroatom, such as a nitrogen atom, an oxygen atom, or a sulfur atom). Optionally, the ring atoms (such as carbon atoms, nitrogen atoms, or sulfur atoms) in the ring structure may be oxo-substituted. 5- to 8-membered monocyclic heteroaryl includes, for example, 5- to 7-membered monocyclic heteroaryl, 5- to 6-membered monocyclic heteroaryl, 5- to 6-membered nitrogen-containing monocyclic heteroaryl, 6-membered nitrogen-containing monocyclic heteroaryl, etc., where the heteroatom in the nitrogen-containing heteroaryl contains at least one nitrogen atom, for example, only 1 or 2 nitrogen atoms, or, contains one nitrogen atom and 1 or 2 other heteroatoms (for example, oxygen atoms and / or sulfur atoms), or, contains 2 nitrogen atoms and 1 or 2 other heteroatoms (for example, oxygen atoms and / or sulfur atoms). Specific examples of monocyclic heteroaryl. Petition 870250075555, dated 08 / 26 / 2025, page 112 / 279 106 / 177 of 5 to 8 members including, but not limited to, furila, thienila, pyrrolila, tiazolila, isotiazolila, tiadiazolila, oxazolila, isoxazolila, oxadiazolila, imidazolila, pyrazolila, base 1,2,3-triazol, 1,2,4-triazolila, 1,2,3oxadiazolila, 1,2,4-oxadiazolila, 1,2,5-oxadiazolila, 1,3,4-oxadiazolila, piridila, 2-piridonila, 4-piridonila, pirimidinila, piridazinila, pirazinila, 1,2,3-triazinila, base 1,3,5-triazina, 1,2,4,5-Tetrazinila, azepantrienila, 1,3-diazaciclo-heptatrienila, azepantetraenila, etc.

[00114] The term 8- to 12-membered fused heteroaryl refers to an unsaturated aromatic ring structure containing 8 to 12 ring atoms (at least one of which is a heteroatom, such as a nitrogen atom, an oxygen atom, or a sulfur atom), which is formed by two or more ring structures sharing two adjacent atoms. Optionally, the ring atoms (such as carbon atoms, nitrogen atoms, or sulfur atoms) in the ring structure may be oxo-substituted. 8- to 12-membered fused heteroaryl includes 8- to 10-membered fused heteroaryl and 8- to 9-membered fused heteroaryl, etc.Specific examples include, but are not limited to: pyrrolopyrrole, pyrrolofuran, pyrazopyrrole, pyrazotiophene, furothiophene, pyrazoxazole, benzofuryl, benzisofuryl, benzothienyl, indoyl, isoindolyl, benzoxazolyl, benzimidazolyl, indazolyl, benzotriazolyl, quinolinyl, 2-quinolinonyl, 4-quinolinonyl, 1-isoquinolinonyl, isoquinolinyl, acridinyl, phenantridinyl, benzopyridazinyl, phthalazinyl, quinazolinyl, quinoxalinyl, purinyl, and naphthyridinyl.

[00115] The term haloalkyl refers to an alkyl group substituted with one or more halogens, where the alkyl group is as defined above.

[00116] The term deuterated alkyl refers to an alkyl substituted with one or more deuterium atoms, where the alkyl is as defined above.

[00117] The term hydroxy refers to an -OH group.

[00118] The term halogen refers to fluorine, chlorine, bromine, or iodine. Petition 870250075555, dated 08 / 26 / 2025, p. 113 / 279 107 / 177

[00119] The term amino refers to an -NH2 group.

[00120] The term nitro refers to a -NO2 group.

[00121] The term acyl refers to the group formed by a carbonyl with an alkyl, alkoxy or amide group, including alkylcarbonyl groups, ester groups and amide groups.

[00122] The term substituted means that the hydrogen in a group is replaced by a substituent, and substituted includes the implicit condition that such substitution conforms to the allowed valences of the substituted atom and the substituent, and that the substitution results in a stable compound. The substituent may not be found in the groups listed above. Optionally, two substituents on the same substituted atom may form a cyclic group, which may be a cycloalkyl or a heterocyclyl, such as a lactam group or a lactone group.

[00123] The term derivative refers to a substance that has a chemical structure similar to that of a compound, but also contains at least one chemical group that is not present in the compound and / or lacks at least one chemical group that is present in the compound. The compound to which the derivative is compared is called the parent compound. Typically, a derivative can be produced from a parent compound in one or more chemical reaction steps.

[00124] The term pharmaceutically acceptable salt refers to a pharmaceutically acceptable organic or inorganic salt of a compound (such as a drug, a drug-ligand compound, or a drug-ligand conjugate). The compound or conjugate may contain at least one amino group or carboxyl group and therefore may form addition salts with the corresponding acid or alkali. Exemplary salts include, but are not limited to, sulfate, trifluoroacetate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphatase, and so on. Petition 870250075555, dated 08 / 26 / 2025, page 114 / 279 108 / 177 fact, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, salicylate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, potassium salt and sodium salt.

[00125] The term solvate refers to a compound formed by a drug-ligand compound or drug-ligand conjugate of the present invention and one or more solvent molecules, wherein the solvent molecules include, but are not limited to, water, ethanol, acetonitrile, isopropanol, DMSO, and ethyl acetate.

[00126] The term pharmaceutical composition refers to a mixture containing one or more compounds of the present invention or physiologically / pharmaceutically acceptable salts or prodrugs thereof and other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and / or excipients. The purpose of the pharmaceutical composition is to promote the administration of drugs to organisms, facilitate the absorption of active ingredients and thus exert biological activity.

[00127] The term transporter refers to a system that can alter how drugs enter the human body and their distribution within the body, controlling the rate of drug release and delivery of drugs to the target. Drug transporter targeting and delivery systems can reduce drug degradation and loss, reduce side effects, and improve bioavailability.

[00128] The term excipient refers to an additive or excipient other than the main drug in a pharmaceutical preparation. Such as adhesives, fillers, disintegrants, lubricants in tablets; supporting matrix in semi-solid preparations, ointments and creams; preservatives, antioxidants, flavoring agents, fragrances, etc. Petition 870250075555, dated 08 / 26 / 2025, page 115 / 279 109 / 177 Solvents, emulsifiers, permeability enhancers, osmotic pressure regulators, colorants, etc. in liquid preparations can all be called excipients.

[00129] The term diluent or filler is mainly used to increase the weight and / or volume of a preparation. The addition of diluent not only ensures a specific volume, but also reduces dosage deviation of the main ingredients and improves compression molding of the drug. BRIEF DESCRIPTION OF THE DRAWINGS

[00130] FIGS. 1A, 1B, 1C, 1D, 1E and 1F show the antitumor effects of the compounds in the cell models BxPC-3, SW620, H1975, HCC827, FaDu and A431, respectively.

[00131] Figures 2A, 2B, 2C, 2D and 2E show the antitumor effect of ADCs in the cell models A431, HCC827, FaDu, N87 and SW620, respectively.

[00132] Figure 3 shows the antitumor effect of ADCs on the heterogeneous tumor cell line A431+ SW620. DETAILED DESCRIPTION OF THE MODALITIES

[00133] The present invention is also described below in conjunction with specific embodiments. It should be understood that these embodiments are used only to illustrate the invention and not to limit the scope of the invention. The experimental methods in the following embodiments that do not specify specific conditions are generally carried out under conventional conditions or under conditions recommended by the manufacturers. Unless otherwise specified, all percentages, proportions, ratios, or parts are calculated by weight. Unless defined otherwise, all professional and scientific terms used herein have the same meaning that is familiar to those skilled in the art. Furthermore, any methods and materials similar or equivalent to those described may be applied to Petition 870250075555, dated 08 / 26 / 2025, p. 116 / 279 110 / 177 methods of the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only.

[00134] The general procedures adopted in the following examples of the present invention are: General Procedure A Preparation of ADCs by conjugation

[00135] Antibody molecules with a monomer content greater than 95% after preliminary purification were exchanged for phosphate buffer containing EDTA using an ultrafiltration centrifuge tube, the concentration being 10 mg / mL. TCEP with an amount 10 times the number of moles of antibody was added for reaction at room temperature for 6 hours. The interchain disulfide bonds of the antibody were opened, and the number of free thiol groups was determined using the Ellman method to determine if all disulfide bonds were opened. Then, a payload with an amount 10 times the number of moles of antibody was added for reaction at room temperature for 6 hours. After the reaction was complete, the reaction system was exchanged for PBS using an ultrafiltration centrifuge tube with a molecular weight cutoff of 30 kDa, and the unconjugated payload was removed, thus obtaining a conjugated ADC (DAR = 8). General Procedure B Preparation of ADCs by site-specific conjugation

[00136] Antibody molecules with a monomer content greater than 95% after preliminary purification were exchanged for phosphate buffer containing EDTA using an ultrafiltration centrifuge tube, at a concentration of 10 mg / mL. TCEP with an amount 8 times the number of moles of antibody was added for reaction at room temperature for 3 hours. The reaction system was then changed for Petition 870250075555, dated 08 / 26 / 2025, pp. 117 / 279 111 / 177 phosphate buffer at pH 6.5 using an ultrafiltration centrifuge tube, and then DHAA (dehydroascorbic acid) with an amount 8 times the number of moles of antibody was added for reaction at room temperature for 3 hours. Then, a payload with an amount 5 times greater than the number of moles of antibody was added for reaction at room temperature for 3 hours. After the reaction was complete, the reaction system was changed to PBS using an ultrafiltration centrifuge tube with a molecular weight cutoff of 30 kDa, and the unconjugated payload was removed, thus obtaining a site-specific conjugation ADC (DAR = 2). General Procedure C Preparation of ADCs by conjugation

[00137] Antibody molecules with a monomer content greater than 95% after preliminary purification were exchanged in 20 mM / sodium acetate / pH 6.0 buffer solution using an ultrafiltration centrifuge tube, with a concentration greater than 5 mg / mL. During the preparation of an ADC, an appropriate amount of antibody after buffer exchange was placed in a reaction tube, TCEP (0.1 M) with an amount 3.6 times the molar amount of antibody was then added, the reaction tube was placed in a constant temperature incubator at 25°C for reaction for 2 hours, the reaction tube was then removed, a binding drug with an amount 5 times the molar amount was added and well mixed, and the reaction tube was placed in a constant temperature incubator at 25°C for reaction for 2 hours.After the reaction was complete, the sample solution was withdrawn and changed to a 20 mM / histidine / pH 5.3 storage buffer using an ultrafiltration centrifuge tube with a molecular weight cutoff of 30 kDa, and the unconjugated payload was removed, thus obtaining a conjugated ADC. (DAR=4). Petition 870250075555, dated 08 / 26 / 2025, pp. 118 / 279 112 / 177 Example 1 - Synthesis of compound D-2 Caption: 2,4,6-colidine

[00138] In a 25 mL single-necked flask, compound D-1 (80 mg, 0.109 mmol, 1.0 eq.) was added and dissolved in dry dichloromethane (4 mL), followed by the addition of 2,4,6-trimethylpyridine (58 μL, 0.438 mmol, 4.0 eq.) and pyridine (0.44 μL, 0.005 mmol, 0.05 eq.), and the reaction solution was cooled to -10 °C. P-Toluenesulfonic anhydride (89.3 mg, 0.274 mmol, 2.5 eq.) was added under nitrogen protection, and the reaction was continued to -10 °C for 20 hours. Then, water (310 μL) was added to the reaction solution. After the reaction solution was brought naturally to room temperature and stirred for 30 minutes, methylamine (methanol solution, 4 mL) was added, and the reaction was continued at room temperature for 46 hours. The reaction solution was then concentrated under reduced pressure. Purification was performed by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound D-2 (white solid, 58 mg, 71%). LC-MS m / z (ES+): [M+H]+: 744.2. Example 2 - Synthesis of compound D-3

[00139] In a 25 mL single-necked flask, compound D-2 (55 mg, 0.074 mmol, 1.0 eq.) was added and dissolved in dichloromethane. Petition 870250075555, dated 08 / 26 / 2025, page 119 / 279 113 / 177 dry ethane (3 mL), followed by the addition of triethylamine (15.4 μL, 0.111 mmol, 1.5 eq.) and di-tert-butyl carbonate (20.4 μL, 0.089 mmol, 1.2 eq.), and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, the reaction solution was concentrated under reduced pressure. Purification was performed by reversed-phase preparative column chromatography, and the preparation solution was lyophilized to provide compound D-3 (white solid, 43 mg, 69%). LC-MS m / z (ES+): [M+H]+: 844.2. Example 3 - Synthesis of compound D-4 (eribulin) Caption: 2,4,6-colidine

[00140] In a 25 mL single-necked flask, compound D-1 (80 mg, 0.109 mmol, 1.0 eq.) was added and dissolved in dry dichloromethane (4 mL), followed by the addition of 2,4,6-trimethylpyridine (58 μL, 0.438 mmol, 4.0 eq.) and pyridine (0.44 μL, 0.005 mmol, 0.05 eq.), and the reaction solution was cooled to -10 °C. p-Toluenesulfonic anhydride (89.3 mg, 0.274 mmol, 2.5 eq.) was added under nitrogen protection, and the reaction was continued at -10 °C for 20 hours. Then, water (310 μL) was added to the reaction solution. After the solution was brought naturally to room temperature and stirred for 30 minutes, isopropanol (4 mL) and ammonium hydroxide (4 mL) were added, and the reaction was continued at room temperature for 3 days. The reaction solution was then concentrated under reduced pressure.The purification was performed by preparative reversed-phase column chromatography, and the preparation solution was lyophilized. Petition 870250075555, dated 08 / 26 / 2025, p. 120 / 279. 114 / 177 used to provide compound D-4 (white solid, LC-MS m / z (ES+): [M+H]+: 730.2. Example 4 - Synthesis of compound D-5 mg, 70%). Legend: 2,4,6-colidine; piperazine

[00141] In a 25 mL single-necked flask, compound D-1 (80 mg, 0.109 mmol, 1.0 eq.) was added and dissolved in dry dichloromethane (4 mL), followed by the addition of 2,4,6-trimethylpyridine (58 μL, 0.438 mmol, 4.0 eq.) and pyridine (0.44 μL, 0.005 mmol, 0.05 eq.), and the reaction solution was cooled to -10 °C. P-Toluenesulfonic anhydride (89.3 mg, 0.274 mmol, 2.5 eq.) was added under nitrogen protection, and the reaction was continued at -10 °C for 20 hours. Then, water (310 μL) was added to the reaction solution. After the reaction solution was brought naturally to room temperature and stirred for 30 minutes, methanol (4 mL) and piperazine (943 mg, 10.9 mmol, 100.0 eq.) were added, and the reaction was continued at room temperature for 3 days. The reaction solution was then concentrated under reduced pressure.Purification was performed by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound D-5 (white solid, 66 mg, 75%). LC-MS m / z (ES+): [M+H]+: 799.2. Example 5 - Synthesis of compound D-6 Caption: 2,4,6-colidine Petition 870250075555, dated 08 / 26 / 2025, pp. 121 / 279 115 / 177

[00142] In a 25 mL single-necked flask, compound D-1 (80 mg, 0.109 mmol, 1.0 eq.) was added and dissolved in dry dichloromethane (4 mL), followed by the addition of 2,4,6-trimethylpyridine (58 μL, 0.438 mmol, 4.0 eq.), epiridine (0.44 μL, 0.005 mmol, 0.05 eq.), and the reaction solution was cooled to -10 °C. Ptoluenesulfonic anhydride (89.3 mg, 0.274 mmol, 2.5 eq.) was added under nitrogen protection, and the reaction was continued at -10 °C for 20 hours. Then, water (310 μL) was added to the reaction solution. After the reaction solution was warmed to room temperature and stirred for 30 minutes, dimethylamine (methanol solution, 8 mL) was added, and the reaction was continued at room temperature for 40 hours. The reaction solution was then concentrated under reduced pressure.Purification was performed by reversed-phase preparative column chromatography, and the preparation solution was lyophilized to provide compound D-6 (white solid, 60 mg, 72%). LC-MS m / z (ES+): [M+H]+: 758.4. Example 6 - Synthesis of compound D-7

[00143] In a 25 mL single-necked flask, compound D-2 (20 mg, 0.027 mmol, 1.0 eq.) was added and dissolved in tetrahydrofuran and water (2 mL), followed by the addition of sodium carbonate (28 mg, 0.269 mmol, 10 eq.) and allyl chloroformate (5.7 μL, 0.054 mmol, 2.0 eq.), and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, the reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound D-7 (white solid, 17 mg, 76%). LC-MS m / z (ES+): [M+H]+: 828.4. Petition 870250075555, dated 08 / 26 / 2025, pp. 122 / 279 116 / 177 Example 7 - Synthesis of compound D-8

[00144] Compound D-8 was synthesized from Compound D-2 and benzyl chloroformate according to the synthesis method of Example 6. LC-MS m / z (ES+): [M+H]+: 878.3. Example 8 - Synthesis of compound D-9

[00145] In a 25 mL single-necked flask, compound D-2 (20 mg, 0.027 mmol, 1.0 eq.) was added and dissolved in dry tetrahydrofuran (2 mL), followed by the addition of triethylamine (7.5 μL, 0.054 mmol, 2.0 eq.) and benzoyl chloride (6.2 μL, 0.054 mmol, 2.0 eq.), and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, the reaction solution was purified by preparative reverse-phase column chromatography, and the preparation solution was lyophilized to provide compound D-9 (white solid, 18 mg, 79%). LC-MS m / z (ES+): [M+H]+: 848.4. Example 9 - Synthesis of compound D-10

[00146] In a 25 mL single-necked vial, compound D-2 (20 mg, 0.027 mmol, 1.0 eq.), HATU (20 mg, 0.054 mmol, 2.0 eq.), HOBt (7.3 mg, 0.054 mmol, 2.0 eq.) and dry DMF (2 mL) were added. Petition 870250075555, dated 08 / 26 / 2025, page 123 / 279 117 / 177 were uniformly dissolved. Under ice-water bath conditions, glacial acetic acid (2.3 μL, 0.040 mmol, 1.5 eq.) and DIEA (9.4 μL, 0.054 mmol, 2.0 eq.) were added sequentially dropwise, and the reaction was allowed to stand at room temperature. After 30 minutes, HPLC showed that the reaction was complete. The reaction solution was purified by preparative reverse-phase column chromatography. The preparation solution was lyophilized to provide compound D-10 (white solid, 14 mg, 66%). LC-MS m / z (ES+): [M+H]+: 886.3. Example 10 - Synthesis of compound D-11

[00147] Compound D-11 was synthesized from Compound D-2 and isobutyric acid according to the synthesis method of Example 9. LCMS m / z (ES+): [M+H]+: 814.4. Example 11 - Synthesis of compound D-12

[00148] Compound D-12 was synthesized from Compound D-2 and depivaloyl chloride according to the synthesis method of Example 8. LC-MS m / z (ES+): [M+H]+: 828.3. Example 12 - Synthesis of compound D-13

[00149] Compound D-13 was synthesized from Compound D-4 according to the synthesis method of Example 2. LC-MS m / z (ES+): Petition 870250075555, dated 08 / 26 / 2025, pp. 124 / 279 118 / 177 [M+H]+: 830.3. Example 13 - Synthesis of compound D-14

[00150] Compound D-14 was synthesized from Compound D-2 and methanesulfonyl chloride according to the synthesis method of Example 8. LC-MS m / z (ES+): [M+H]+: 822.3. Example 14 - Synthesis of compound D-15

[00151] Compound D-15 was synthesized from compound D-2 and difluoroacetic anhydride according to the synthesis method of Example 8. LC-MS m / z (ES+): [M+H]+: 822.3. Example 15 - Synthesis of compound D-16

[00152] Compound D-16 was synthesized from compound D-4 and cis-3-hydroxycyclobutanecarboxylic acid S1 according to the synthesis method of Example 9. LC-MS m / z (ES+): [M+H]+: 828.3. Example 16 - Synthesis of compound D-17 Petition 870250075555, dated 08 / 26 / 2025, pp. 125 / 279 119 / 177

[00153] Compound D-17 was synthesized from compound D-4 and trans-3-hydroxycyclobutanecarboxylic acid S2 according to the synthesis method of Example 9. LC-MS m / z (ES+): [M+H]+: 828.3. Example 17 - Synthesis of compound D-18 Caption: proton sponge

[00154] Compound D-13 (61 mg, 0.074 mmol, 1.0 eq.) was weighed and placed in a 25 mL single-necked flask and dissolved in dry dichloromethane (6 mL), followed by the addition of 1,8bis(dimethylamino)naphthalene (48 mg, 0.222 mmol, 3.0 eq.) and trimethyloxonium tetrafluoroborate (33 mg, 0.222 mmol, 3.0 eq.), and the reaction was left at room temperature overnight. After the reaction was considered complete by TLC monitoring, the reaction solution was filtered, concentrated under reduced pressure, and purified by TLC to give compound D-18 (a white vesicular solid, 56 mg, 90%). LC-MS m / z (ES+): [M+H]+: 844.4. Example 18 - Synthesis of compound D-19

[00155] Compound D-18 (56 mg, 0.066 mmol, 1.0 eq.) was dissolved in dry dichloromethane (4 mL), followed by the addition of trifluoroacetic acid (200 μL), and the reaction was left at room temperature for 40 minutes. After the reaction was considered complete by TLC monitoring, the reaction solution was adjusted to pH 8 with sodium bicarbonate, extracted with dichloromethane, dried, filtered, and concentrated to provide a crude product of compound D-19. Petition 870250075555, dated 08 / 26 / 2025, pp. 126 / 279 120 / 177 Example 19 - Synthesis of compound D-20

[00156] Compound D-20 was synthesized from Compound D-19 and cis-3-hydroxycyclobutanecarboyl acid S1, according to the synthesis method of Example 9. LC-MS m / z (ES+): [M+H]+: 842.3. Example 20 - Synthesis of compound S5 Caption: proton sponge Step 1: S3 compound

[00157] cis-3-hydroxycyclobutanecarboxylic acid S1 (150 mg, 1.29 mmol, 1.0 eq.) and potassium carbonate (536 mg, 3.88 mmol, 3.0 eq.) were weighed and placed in a 25 mL single-necked flask, followed by the addition of DMF (3 mL) and benzyl bromide (230 μL, 1.94 mmol, 1.5 eq.), and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, water was added to the reaction solution, which was then extracted with ethyl acetate, dried, filtered, concentrated, and purified by column chromatography (dichloromethane / methanol = 30:1) to give compound S3 (yellow oil, 207 mg, 78%). Step 2: S4 compound

[00158] Compound S3 (173 mg, 0.839 mmol, 1.0 eq.) was weighed and placed in a 25 mL single-necked flask and dissolved in dry dichloromethane (5 mL), followed by the addition of 1,8bis(dimethylamino)naphthalene (539 mg, 2.52 mmol, 3.0 eq.) and trimethyloxonium tetrafluoroborate (372 mg, 2.52 mmol, 3.0 eq.), and the reaction was Petition 870250075555, dated 08 / 26 / 2025, pp. 127 / 279 121 / 177 left at room temperature overnight. After the reaction was considered complete by TLC monitoring, the reaction solution was filtered, concentrated under reduced pressure, and purified by column chromatography (petroleum ether:ethyl acetate = 6:1) to give compound S4 (colorless oily substance, 168 mg, 91%). Step 2: S5 compound

[00159] Compound S4 (6 mg, 0.027 mmol, 1.0 eq.) was weighed and placed in a 25 mL single-necked flask and dissolved in anhydrous ethanol (1 mL), followed by the addition of 5% Pd / C (3 mg) and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, the resulting reaction solution was filtered and concentrated to provide a crude product of compound S5. Example 21 - Synthesis of compound D-21

[00160] Compound D-21 was synthesized from Compound D-4 and cis-3-methoxycyclobutane carboxylic acid S5 according to the synthesis method of Example 9. LC-MS m / z (ES+): [M+H]+: 842.3. Example 22 - Synthesis of compound S7

[00161] In a 25 mL single-necked flask, compound S6 (2.0 g, 4.84 mmol, 1.0 eq, synthesis method refers to patent CN111051330 A) and dry tetrahydrofuran (4 mL) were added and completely dissolved, then 5% Pd / C (100 mg) was added, and the hydrogenation reaction was carried out overnight. After completion, the mixture was filtered, and the filtrate was concentrated to Petition 870250075555, dated 08 / 26 / 2025, pp. 128 / 279 122 / 177 provide compound S7 (white solid, 1.17 g, 87%). LC-MS m / z (ES+): [M+H]+: 280.1. Example 23 - Synthesis of compound S9

[00162] In a 25 mL single-necked flask, compound S8 (1.0 g, 2.51 mmol, 1.0 eq, synthesis method refers to the synthesis of compound M2 in patent application CN113827736 A), pentafluorophenol (508 mg, 2.76 mmol, 1.1 eq.), DCC (570 mg, 2.76 mmol, 1.1 eq.) and DMF (8 mL) were added, and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, the reaction solution was filtered to provide the crude filtrate of compound S9 for further use. LC-MS m / z (ES+): [M+H]+: 565.1. Example 24 - Synthesis of compound S10

[00163] Compound S7 (771 mg, 2.76 mmol, 1.1 eq.), DMF (8 mL) and DIEA (656 μL, 3.76 mmol, 1.5 eq.) were added to a 50 mL single-necked flask, and the crude filtrate of compound S9 above was added to an ice-cold water bath, and the reaction was left at room temperature overnight. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S10. Petition 870250075555, dated 08 / 26 / 2025, pp. 129 / 279 123 / 177 (white solid, 778 mg, 47%). LC-MS m / z (ES+): [M+H]+: 660.2. Example 25 - Synthesis of compound S12

[00164] Compound D-3 (40 mg, 0.047 mmol, 1.0 eq.), the compound S11 (52.4 mg, 0.142 mmol, 3.0 eq., synthesis method refers to the synthesis of compound 1 in patent CN111686259 A), zinc acetate (26.1 mg, 0.142 mmol, 3.0 eq.) and 4A molecular sieve (60 mg) were added sequentially to a 25 mL single-necked flask, followed by the addition of dry toluene (4 mL), and the reaction mixture was replaced with nitrogen three times, then heated with stirring to 100 °C. After 2 hours, the reaction was terminated, allowed to cool to room temperature, filtered, and the filtrate was concentrated under reduced pressure. Purification was performed by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S12 (white solid, 37 mg, 68%). LC-MS m / z (ES+): [M+Na]+: 1174.2. Example 26 - Synthesis of compound S13

[00165] In a 25 mL single-necked flask, compound S12 (30 mg, 0.026 mmol, 1.0 eq.) and dry DMF (1.5 mL) were added and completely dissolved, then DBU (4.3 μL, 0.029 mmol, 1.1 eq.) was added, and the reaction was left at room temperature. The consumption of compound S12 was considered to be complete from the Petition 870250075555, dated 08 / 26 / 2025, pp. 130 / 279 124 / 177 TLC monitoring, and no post-treatment was required for the reaction. The next reaction was performed directly with a crude solution of compound S13. LC-MS m / z (ES+): [M+Na]+: 953.3. Example 27 - Synthesis of compound S14

[00166] In another 25 mL single-necked flask, compound S10 (18.9 mg, 0.029 mmol, 1.1 eq.), HATU (11.9 mg, 0.031 mmol, 1.2 eq.), HOBt (4.2 mg, 0.031 mmol, 1.2 eq.) and dry DMF (1.5 mL) were added sequentially and dissolved uniformly. Then the crude solution of compound S13 and DIEA (5.4 μL, 0.031 mmol, 1.2 eq.) was added dropwise under ice-cold water conditions, and the reaction was allowed to proceed to room temperature. After 30 minutes, HPLC showed the completion of the reaction. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S14 (white solid, 23 mg, 56%). LC-MS m / z (ES+): [M-99]+: 1472.2 (ion fragment of compound S14 after removal of the Boc protecting group and addition of hydrogen ion). Example 28 - Synthesis of compound L1

[00167] In a 25 mL single-necked flask, compound S14 (20 mg, 0.013 mmol, 1.0 eq.) was completely dissolved in nitrome Petition 870250075555, dated 08 / 26 / 2025, pp. 131 / 279 125 / 177 ethane (2 mL), then zinc bromide (57 mg, 0.25 mmol, 20.0 eq.) was added, and the reaction was left at room temperature for 30 minutes and monitored by HPLC. After the reaction was considered complete, the resulting reaction solution was concentrated under reduced pressure at 45 °C using a water pump to provide a crude product. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound L-1 (white solid, 9.2 mg, 55%) and compound L-1' (white solid, 5.2 mg, 31%). L-1: LC-MS m / z (ES+): [M+Na]+: 1337.3. L-1': LC-MS m / z (ES+): [M+Na]+: 1337.3. Example 29 - Synthesis of compound S15

[00168] Compound D-1 (50 mg, 0.068 mmol, 1.0 eq.), compound S11 (27.7 mg, 0.075 mmol, 1.1 eq.), zinc acetate (25.1 mg, 0.137 mmol, 2.0 eq.) and 4A molecular sieve (100 mg) were added sequentially to a 25 mL single-necked flask, followed by the addition of dry toluene (5 mL). The reaction mixture was replaced with nitrogen three times, then heated with stirring to 100 °C. After 3 hours, the reaction was abruptly stopped, allowed to cool to room temperature, filtered, and the filtrate concentrated under reduced pressure. Purification was performed by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to give compound S15 (white solid, 42 mg, 59%). LC-MS m / z (ES+): [M+Na]+: 1061.3. Example 30 - Synthesis of compound S16 Petition 870250075555, dated 08 / 26 / 2025, pp. 132 / 279 126 / 177

[00169] In a 25 mL single-necked flask, compound S15 (37 mg, 0.036 mmol, 1.0 eq.) and dry DMF (1.5 mL) were added and completely dissolved, then DBU (5.9 μL, 0.039 mmol, 1.1 eq.) was added, and the reaction was left at room temperature. The consumption of compound S15 was considered complete based on TLC monitoring, and no post-treatment was required for the reaction. The next reaction was carried out directly with a crude solution of compound S16. LC-MS m / z (ES+): [M+Na]+: 839.1. Example 31 - Synthesis of compound S17

[00170] In another 25 mL single-necked flask, compound S10 (25.8 mg, 0.039 mmol, 1.1 eq.), HATU (16.2 mg, 0.043 mmol, 1.2 eq.), HOBt (5.8 mg, 0.043 mmol, 1.2 eq.) and dry DMF (1.5 mL) were added sequentially and dissolved uniformly. The above crude solution of compound S16e DIEA (7.4 μL, 0.043 mmol, 1.2 eq.) was added dropwise under ice-cold water bath conditions, and the reaction was allowed to stand at room temperature. After 30 minutes, HPLC showed the completion of the reaction. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S17 (white solid, 26 mg, 50%). LC-MS m / z (ES+): [M+H]+: 1459.2. Example 32 - Synthesis of compound L-2 Petition 870250075555, dated 08 / 26 / 2025, pp. 133 / 279 127 / 177

[00171] In a 25 mL single-necked flask, compound S17 (21 mg, 0.014 mmol, 1.0 eq.) was completely dissolved in nitromethane (2 mL), then zinc bromide (65 mg, 0.288 mmol, 20.0 eq.) was added, and the reaction was allowed to stand at room temperature for 30 minutes and monitored by HPLC. After the reaction was considered complete, the resulting reaction solution was concentrated under reduced pressure at 45 °C using a water pump to provide a crude product. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound L-2 (white solid, 10.7 mg, 57%) and compound L-2' (white solid, 5.4 mg, 29%). L-2: LC-MS m / z (ES+): [M+Na]+: 1324.3. L-2': LC-MS m / z (ES+): [M+Na]+: 1324.3. Example 33 - Synthesis of compound L-3

[00172] Compound L-3 was synthesized from compound S13 and compound S18 (see patent WO 2022171101 for synthesis method) according to the synthesis method of Example 27. LC-MS m / z (ES+): [M-99]+: 1285.1 (fragment ion of compound L-3 after removal of the Boc protecting group and addition of the hydrogen ion). Example 34 - Synthesis of compound D-22 Petition 870250075555, dated 08 / 26 / 2025, pp. 134 / 279 128 / 177

[00173] In a 25 mL single-necked flask, compound D-4 (53 mg, 0.073 mmol, 1.0 eq.) was added and dissolved in dry dichloromethane (3 mL), followed by the addition of triethylamine (30 μL, 0.218 mmol, 3.0 eq.), DMAP (1.8 mg, 0.015 mmol, 0.2 eq.) and di-tert-butyl dicarbonate (42 μL, 0.182 mmol, 2.5 eq.), and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by TLC monitoring, the reaction solution was concentrated under reduced pressure. Purification was performed by reversed-phase preparative column chromatography, and the preparation solution was lyophilized to provide compound D-22 (white solid, 36 mg, 53%). LC-MS m / z (ES+): [M+H]+: 930.2. Example 35 - Synthesis of compound S19 D-22 S19

[00174] Compound S19 was synthesized from Compound D-22 and Compound S11 according to the synthesis method of Example 25. LCMS m / z (ES+): [M+Na]+: 1260.2. Example 36 - Synthesis of compound S20 A crude solution of compound S20 was synthesized from

[00175] Petition 870250075555, dated 08 / 26 / 2025, pp. 135 / 279 129 / 177 compound S19 according to the synthesis method of Example 26, and placed in the next reaction step directly without posttreatment. LC-MS m / z (ES+): [M+Na]+: 1038.3. Example 37 - Synthesis of compound S21

[00176] Compound S21 was synthesized from compound S20 and compound S10 according to the synthesis method of Example 27.TOF m / z: [M+H]+: 1657.5. Example 38 - Synthesis of compound L-4

[00177] Compound L-4 was synthesized from compound S21 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+Na]+: 1323.3. Example 39 - Synthesis of compound S22

[00178] Compound S22 was synthesized from Compound D-5 according to the synthesis method of Example 2. LC-MS m / z (ES+): [M+H]+: 898.3. Example 40 - Synthesis of compound S23 S22 S23

[00179] Compound S23 was synthesized from compound S22 and compound S11 according to the synthesis method of Example 25. LCMS m / z (ES+): [M+Na]+:1229.3. Petition 870250075555, dated 08 / 26 / 2025, pp. 136 / 279 130 / 177 Example 41 - Synthesis of compound S24

[00180] A crude solution of compound S24 was synthesized from compound S23 according to the synthesis method of Example 26, and placed in the next reaction step directly without posttreatment. LC-MS m / z (ES+): [M+Na]+: 1007.3.

[00181] Example 42 - Synthesis of compound S25

[00182] Compound S25 was synthesized from compound S24 and compound S10 according to the synthesis method of Example 27. TOF m / z: [M+H]+: 1626.5. Example 43 - Synthesis of compound L-5

[00183] Compound L-5 was synthesized from compound S25 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+Na]+: 1392.4. Example 44 - Synthesis of compound S26 Petition 870250075555, dated 08 / 26 / 2025, pp. 137 / 279 131 / 177

[00184] Compound S26 was synthesized from Compound D-6 and Compound S11, according to the synthesis method of Example 25. LCMS m / z (ES+): [M+Na]+: 1088.3. Example 45 - Synthesis of compound S27

[00185] A crude solution of compound S27 was synthesized from compound S26 according to the synthesis method of Example 26, and placed in the next reaction step directly without posttreatment. LC-MS m / z (ES+): [M+Na]+: 866.2. Example 46 - Synthesis of compound S28g

[00186] Compound S28 was synthesized from compound S27 and compound S10 according to the synthesis method of Example 27. LCMS m / z (ES+): [M+Na]+: 1485.5. Example 47 - Synthesis of compound L-6

[00187] Compound L-6 was synthesized from compound S28 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+Na]+:1351.3. Example 48 - Synthesis of compound L-7

[00188] Compound L-7 was synthesized according to the method of Petition 870250075555, dated 08 / 26 / 2025, pp. 138 / 279 132 / 177 Synthesis of compound ER-001235638 in patent CN108883198A. Example 49 - Synthesis of compound L-8

[00189] Compound L-8 was synthesized according to the synthesis method of ER-001159569 in patent CN108883198A. Example 50 - Synthesis of compound S29

[00190] Compound S29 was synthesized from Compound D-12 and Compound S11, according to the synthesis method of Example 25. LC-MS m / z (ES+): [M+Na]+: 1158.4. Example 51 - Synthesis of compound S30

[00191] A crude solution of compound S30 was synthesized from compound S29, according to the synthesis method of Example 26, and placed in the next reaction step directly without posttreatment. LC-MS m / z (ES+): [M+Na]+:936.5. Example 52 - Synthesis of compound S31 Petition 870250075555, dated 08 / 26 / 2025, pp. 139 / 279 133 / 177

[00192] Compound S31 was synthesized from compound S30 and compound S10, according to the synthesis method of Example 27.TOF m / z: [M+H]+: 1555.7. Example 53 - Synthesis of compound L-9

[00193] Compound L-9 was synthesized from compound S31, according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+Na]+: 1421.7. Example 54 - Synthesis of compound S32

[00194] Compound S32 was synthesized from Compound D-14 and Compound S11, according to the synthesis method of Example 25. LC-MS m / z (ES+): [M+Na]+: 1152.5. Example 55 - Synthesis of compound S33

[00195] A crude solution of compound S33 was synthesized from compound S32 according to the synthesis method of Example 26, and placed in the next reaction step directly without powder. Petition 870250075555, dated 08 / 26 / 2025, pp. 140 / 279 134 / 177 treatment. LC-MS m / z (ES+): [M+Na]+:930.4. Example 56 - Synthesis of compound S33

[00196] Compound S33 was synthesized from compound S32 and compound S10, according to the synthesis method of Example 27.TOF m / z: [M+H]+: 1549.7. Example 57 - Synthesis of compound L-10

[00197] Compound L-10 was synthesized from compound S33 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+Na]+: 1415.6. Example 58 - Synthesis of compound S34 D-15 S34

[00198] Compound S34 was synthesized from Compound D-15 and Compound S11, according to the synthesis method of Example 25. LCMS m / z (ES+): [M+Na]+: 1152.4. Example 59 - Synthesis of compound S35 Petition 870250075555, dated 08 / 26 / 2025, pp. 141 / 279 135 / 177

[00199] A crude solution of compound S35 was synthesized from compound S34, according to the synthesis method of Example 26, and placed in the next reaction step directly without posttreatment. LC-MS m / z (ES+): [M+Na]+:930.3. Example 60 - Synthesis of compound S36

[00200] Compound S36 was synthesized from compound S35 and compound S10, according to the synthesis method of Example 27. TOF m / z: [M+H]+: 1549.6. Example 61 - Synthesis of compound L-11

[00201] Compound L-11 was synthesized from compound S36, according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+Na]+: 1415.6. Example 62 - Synthesis of compound S39 Petition 870250075555, dated 08 / 26 / 2025, pp. 142 / 279 136 / 177 Step 1: Synthesis of compound S38

[00202] In a 25 mL single-necked flask, compound S37 (400 mg, 1.13 mmol, 1.0 eq.), pentafluorophenol (228 mg, 1.24 mmol, 1.1 eq.), DCC (255 mg, 1.24 mmol, 1.1 eq.) and DMF (4 mL) were added, and the reaction was left at room temperature overnight. After the reaction was considered complete by TLC monitoring, the reaction solution was filtered to provide the crude filtrate of compound S38 for further use. Step 2: Synthesis of compound S39

[00203] Compound S7 (377mg, 1.35 mmol, 1.2eq.), DMF (4 mL) and DIEA (235 μL, 1.35 mmol, 1.2 eq.) was added to a 25 mL single-necked flask, and the crude filtrate of compound S38 above was added to an ice-cold water bath, and the reaction was left at room temperature overnight. The reaction solution was purified by preparative reverse-phase column chromatography, and the preparation solution was lyophilized to provide compound S39 (white solid, 543 mg, 78%). LC-MS m / z (ES+): [M+H]+: 617.1. Example 63 - Synthesis of compound S44 Caption: diethylamine Step 1: Synthesis of compound S41

[00204] In a 2 L single-necked flask, Fmoc-L-glutamic acid-5-tert-butyl ester (S40, 200 g, 470 mmol, 1.0 eq.), propargylamine (28.5 g, 517 mmol, 1.1 eq.) and 400 mL of DMF were added and completely dissolved, then the resulting solution was Petition 870250075555, dated 08 / 26 / 2025, pp. 143 / 279 137 / 177 cooled to 0°C in an ice water bath. EDCI (108.2 g, 564 mmol, 1.2 eq.), HOBt (76.2 g, 564 mmol) and DIEA (117 mL, 705 mmol, 1.5 eq.) were added, and the reaction was left at room temperature for 2 hours and the reaction was monitored by TLC until completion. After the reaction was complete, the reaction solution was poured into 2 L of water. Extraction was performed three times with ethyl acetate (500 mL χ 3). The organic phases were combined, washed twice with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The resulting reaction solution was then filtered to remove sodium sulfate, and the filtrate was concentrated to provide a crude product. The crude product was purified using petroleum ether / ethyl acetate (2 / 1) to give compound S41 (100.9 g, 48% yield). LC-MS m / z (ES+): [M+H]+: 463.2. Step 2: Synthesis of compound S42

[00205] In a 1 L single-necked flask, S41 (100.0 g) was added and dissolved in 500 mL of dichloromethane, followed by the addition of 200 mL of trifluoroacetic acid. The reaction was left at room temperature for 2 hours and the reaction was monitored by TLC until completion. After the reaction was complete, the reaction solution was concentrated to remove dichloromethane and a portion of trifluoroacetic acid, and a crude product was obtained. Methyl tert-butyl ether was added to the crude product, and a white solid was precipitated, filtered, and dried to give compound S42 (77.5 g, 87% yield), LC-MS m / z (ES-): [M - H]-: 405.1. Step 3: Synthesis of compound S43

[00206] In a 2 L single-necked flask, S42 (77.0 g) was added and dissolved in 150 mL of DMF, followed by the addition of 38 mL of diethylamine. The reaction was left at room temperature for 2 hours and the reaction was monitored by TLC until completion. After Petition 870250075555, dated 08 / 26 / 2025, pp. 144 / 279 138 / 177 to complete the reaction, 800 mL of methyl tert-butyl ether was added to the reaction solution. A white solid was precipitated, filtered, and dried to give compound S43 (33.7 g, 96.6% yield), LC-MS m / z (ES-): [M - H]-: 183.1. Step 4: Synthesis of compound S44

[00207] In a 100 mL single-necked flask, compound S43 (10.02 g, 54.4 mmol, 1.5 eq.), compound S8 (14.48 g, 36.3 mmol, 1.0 eq.) and 100 mL of DMF were added and dissolved, followed by the addition of EEDQ (13.5 g, 54.8 mmol, 1.5 eq.). The reaction was left at room temperature for 2 hours and the reaction was monitored by HPLC until completion. After the reaction was complete, the reaction solution was purified by preparative liquid chromatography to provide the product preparation solution, which was then lyophilized to provide compound S44 (9.94 g, 48% yield), LC-MS m / z (ES-): [M - H]-: 563.2. Example 64 - Synthesis of compound S47 Step 1: Synthesis of compound S45

[00208] In a 25 mL single-necked flask, compound S44 (230 mg, 0.407 mmol, 1.0 eq.), pentafluorophenol (83 mg, 0.448 mmol, 1.1 eq.), DCC (93 mg, 0.448 mmol, 1.1 eq.) and DMF (3.5 mL) were added, and the reaction was left at room temperature for the Petition 870250075555, dated 08 / 26 / 2025, pp. 145 / 279 139 / 177 night. After the reaction was considered complete by TLC monitoring, the reaction solution was filtered to provide the crude filtrate of compound S45 for further use. Step 2: Synthesis of compound S46

[00209] In a 25 mL single-necked flask, compound S39 (301 mg, 0.489 mmol, 1.2 eq.) and dry DMF (3 mL) were added and completely dissolved, then DBU (79 μL, 0.529 mmol, 1.3 eq.) was added, and the reaction was left at room temperature. The consumption of compound S39 was considered complete by monitoring the TLC, and no post-treatment was required for the reaction. The next reaction was carried out directly with a crude solution of compound S46. Step 3: Synthesis of compound S47

[00210] Under an ice water bath, the crude filtrate of compound S45 was mixed with the crude solution of S46, and DIEA (71 μL, 0.407 mmol, 1.0 eq.) was slowly added dropwise, and the reaction was left at room temperature for 40 minutes. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to give compound S47 (white solid, 258 mg, 67%). LC-MS m / z (ES+): [M+H]+: 941.3. Example 65 - Synthesis of compound S50 THE

[00211] In a 150 mL single-necked flask, compound S48 (667 mg, 3.28 mmol, 1.0 eq.), S49 (1.58 g, 3.94 mmol, 1.2 eq., synthesis method refers to the synthesis of compound 11 in patent WO 0152900 A2), EDCI (944 mg, 4.92 mmol, 1.5 eq.), HOBt (665 mg, 4.92 mmol, 1.5 eq.) and dry dichloromethane (60 mL) were added if Petition 870250075555, dated 08 / 26 / 2025, pp. 146 / 279 140 / 177 quantitatively and uniformly dissolved. DIEA (1.14 mL, 6.56 mmol, 2.0 eq.) was added dropwise under ice-cold water bath conditions, and the reaction was allowed to stand at room temperature. After 2 hours, the reaction was considered complete by TLC monitoring. The reaction solution was abruptly stopped with saturated aqueous ammonium chloride, extracted with dichloromethane, dried, filtered, concentrated, and purified by column chromatography (petroleum ether / ethyl acetate = 30:1) to give compound S50 (a yellow oil of 1.3 g, 67%). LC-MS m / z (ES+): [M+H]+: 588.4. Example 66 - Synthesis of compound S51 Caption: sodium ascorbate

[00212] In a 25 mL single-necked flask, compound S47 (58 mg, 0.061 mmol, 1.0 eq.), compound S50 (36 mg, 0.061 mmol, 1.0 eq.), copper(II) sulfate pentahydrate (31 mg, 0.123 mmol, 2.0 eq.), sodium ascorbate (24 mg, 0.123 mmol, 2.0 eq.) and DMF (2 mL) were added, then water (1 mL) was added in an ice-cold water bath, and the reaction was allowed to stand at room temperature. After 30 minutes, HPLC showed the completion of the reaction. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S51 (white solid, 85 mg, 91%). LC-MS m / z (ES+): [M+2H]2+: 764.7. Example 67 - Synthesis of compound S52 Petition 870250075555, dated 08 / 26 / 2025, pp. 147 / 279 141 / 177

[00213] Compound S52 was synthesized from compound S51 and compound S30 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+H+Na]2+: 1223.8. Example 68 - Synthesis of compound L-12

[00214] In a 25 mL single-necked flask, compound S52 (19 mg, 0.0078 mmol, 1.0 eq.) and enitromethane (2 mL) were added and completely dissolved, then zinc bromide (124 mg, 0.548 mmol, 70.0 eq.) was added, and the reaction was left at room temperature for 45 minutes. The reaction solution was concentrated under reduced pressure to provide a crude product. The crude product was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound L-12 (white solid, 9.2 mg, 55%). L-12: LC-MS m / z (ES+): [M+2H]2+: 1050.3. Example 69 - Synthesis of compound S53

[00215] Compound S53 was synthesized from compound S51 and compound S33 according to the synthesis method of Example 27. Petition 870250075555, dated 08 / 26 / 2025, pp. 148 / 279 142 / 177 LC-MS m / z (ES+): [M+2H]2+: 1209.9. Example 70 - Synthesis of compound L-13

[00216] Compound L-13 was synthesized from compound S53 according to the synthesis method of Example 68. LC-MS m / z (ES+): [M+2H]2+: 1047.4. Example 71 - Synthesis of compound S54

[00217] Compound S54 was synthesized from compound S51 and compound S35 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H+Na]2+: 1220.8. Example 72 - Synthesis of compound L-14

[00218] Compound L-14 was synthesized from compound S54 according to the synthesis method of Example 68. LC-MS m / z (ES+): [M+2H]2+: 1047.4. Example 73 - Synthesis of compound S57 Petition 870250075555, dated 08 / 26 / 2025, pp. 149 / 279 143 / 177 Step 1: Synthesis of compound S56

[00219] In a 25 mL single-necked flask, compound S55 (400 mg, 2.36 mmol, 1.0 eq.), pentafluorophenol (479 mg, 2.60 mmol, 1.1 eq.), DCC (537 mg, 2.60 mmol, 1.1 eq.) and DMF (4 mL) were added, and the reaction was left at room temperature for 4 hours. After the reaction was considered complete by TLC monitoring, the reaction solution was filtered to provide the crude filtrate of compound S56 for further use. Step 2: Synthesis of compound S57

[00220] Compound S43 (436 mg, 2.36 mmol, 1.0 eq.) and DMF (7 mL) were added to the crude filtrate of compound S56 above, and DIEA (412 μL, 2.36 mmol, 1.0 eq.) was added to an ice water bath, and the reaction was left at room temperature for 2 hours. After the reaction was considered complete by HPLC monitoring, the reaction solution was purified by preparative reverse-phase column chromatography, and the preparation solution was lyophilized to provide compound S57 (white solid, 649 mg, 82%). LC-MS m / z (ES+): [M+Na]+: 358.2. Example 74 - Synthesis of compound S59

[00221] Compound S59 was synthesized from compound S57 and compound S46 according to the synthesis method of Example 64. LC-MS m / z (ES+): [M+H]+: 712.0. Petition 870250075555, dated 08 / 26 / 2025, pp. 150 / 279 144 / 177 Example 75 - Synthesis of compound S60

[00222] Compound S60 was synthesized from compound S59 and compound S30 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H]2+: 804.4. Example 76 - Synthesis of compound S61

[00223] Compound S50 (201 mg, 0.342 mmol, 1.0 eq.) was dissolved in dry dichloromethane (4 mL), then trifluoroacetic acid (800 pL) was added, and the reaction was left at room temperature. After 30 hours, the reaction solution was concentrated under reduced pressure. The crude product was purified by reversed-phase preparative column chromatography, and the preparation solution was lyophilized to provide compound S61 (white solid, 98 mg, 69%). LC-MS m / z (ES-): [M - H]-: 418.2. Example 77 - Synthesis of compound L-15 Caption: sodium ascorbate

[00224] In a 25 mL single-necked flask, compound S60 (25 mg, 0.016 mmol, 1.0 eq.), compound S61 (7.8 mg, 0.019 mmol, 1.2 eq.), copper(II) sulfate pentahydrate (19 mg, 0.078 mmol, 5.0 eq.), sodium ascorbate (15 mg, 0.078 mmol, 5.0 eq.) and DMF (2 mL) were added, then water (1 mL) was added in a ba Petition 870250075555, dated 08 / 26 / 2025, pp. 151 / 279 145 / 177 nho of ice water, and the reaction was left at room temperature. After 30 minutes, HPLC showed the completion of the reaction. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound L-15 (white solid, 21 mg, 66%). LC-MS m / z (ES+): [M+H+Na]2+: 1024.9. Example 78 - Synthesis of compound S62

[00225] Compound S62 was synthesized from compound S59 and compound S33 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H]2+: 801.3. Example 79 - Synthesis of compound L-16 Caption: sodium ascorbate

[00226] Compound L-16 was synthesized from compound S62 and compound S61 according to the synthesis method of Example 77. LC-MS m / z (ES+): [M+H+NH4]2+: 1019.5. Example 80 - Synthesis of compound S63

[00227] Compound S63 was synthesized from compound S59 and compound S35 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H]2+: 801.0. Example 81 - Synthesis of compound L-17 Petition 870250075555, dated 08 / 26 / 2025, pp. 152 / 279 146 / 177 Caption: sodium ascorbate

[00228] Compound L-17 was synthesized from compound S63 and compound S61 according to the synthesis method of Example 77. LC-MS m / z (ES+): [M+2H]2+:1010.9. Example 82 - Synthesis of compound S68 ° I° I 1) piperidine, DMF ,χ HFIP / CH2CI2r 2)Ac2O, DIEA, O1O O1ODMFS67S68 Caption: stage; piperidine; repeat steps a and b

[00229] Step 1: Resin Loading: 4.6 g of 2-chlorotritile chloride resin beads (1.05 mmol / g) were weighed and placed in a resin reactor and swollen in DMF for 1 hour. After swelling, the solvent was filtered and a solution (30 mL) of Fmoc-sarcosine (1.5 g, 4.8 mmol, 1.0 eq.) and DIEA (1.7 mL, 9.6 mmol, 2.0 eq.) in DMF was added to the resin, and a resin reactor was stirred at room temperature for 4 hours. After filtration, the resin was blocked with MeOH / DlEA / DMF (5 mL / 2.5 mL / 25 mL) for 30 minutes, and then the resin was thoroughly washed with DMF (8 times) to provide compound S64. Step 2: Extension of polysarcosine compounds

[00230] Step a: The resin was treated with piperidine / DMF (6 mL / 24 mL) twice, 20 minutes each time. The resin was then washed with DMF (8 times).

[00231] Step b: A solution (30 mL) of Fmoc-sarcosine (4.5 g, 14.4 mmol, 3.0 eq.), HATU (5.5 g, 14.4 mmol, 3.0 eq.), HOBt (1.9 g, Petition 870250075555, dated 08 / 26 / 2025, pp. 153 / 279 147 / 177 14.4 mmol, 3.0 eq.) and DIEA (4.2 mL, 24 mmol, 5.0 eq.) in DMF was added to the resin, and a resin reactor was stirred at room temperature for 2 hours. The resin was then washed with DMF (8 times).

[00232] Steps a and b were repeated until the length of the polysarcosine compound on the resin reached 16 peptides, thus obtaining compound S66. Step 3: Acetylation

[00233] The resin was treated with piperidine / DMF (6 mL / 24 mL) twice for 20 minutes each time. The resin was then washed with DMF (8 times).

[00234] The resin was then treated with acetic anhydride / DIEA / DMF (5 mL / 10 mL / 15 mL) twice, 1 hour each time. The resin was then washed with DMF (8 times) to provide compound S67. Step 4: Resin cleavage

[00235] Polysarcosine oligomers were cleaved from a resin with an HFIP / CH2Cl2 solution (6 mL / 24 mL) for 30 minutes. The resin was filtered, the filtrate was concentrated under reduced pressure, and the crude product was purified by a reversed-phase preparative column, and the preparation was lyophilized to provide compound S68 (white solid, 1.7 g, 30%). LC-MS m / z (ES+): [M+2NH4]2+: 616.4. Example 83 - Synthesis of compound S70

[00236] In a 25 mL single-necked flask, compounds S68 (93 mg, 0.078 mmol, 1.0 eq.), S69 (17 mg, 0.078 mmol, 1.0 eq.), HATU (45 mg, 0.117 mmol, 1.5 eq.), HOBt (16 mg, 0.117 mmol, 1.5 eq.), and dry DMF (2.5 mL) were added sequentially and dissolved uniformly. DIEA (27 μL, 0.156 mmol, 2.0 eq.) was added dropwise. Petition 870250075555, dated 08 / 26 / 2025, pp. 154 / 279 148 / 177 drop by drop under ice water bath conditions, and the reaction was allowed to stand at room temperature. After 1 hour, HPLC showed completion of the reaction. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S70 (white solid, 80 mg, 73%). LC-MS m / z (ES+): [M+H]+: 1397.1. Example 84 - Synthesis of compound L-18 Caption for the figure above: sodium ascorbate

[00237] Compound L-18 was synthesized from compound S60 and compound S70 according to the synthesis method of Example 77. TOF m / z: [M+Na]+: 3026.5. Example 85 - Synthesis of compound L-19 Caption: sodium ascorbate

[00238] Compound L-19 was synthesized from compound S62 and compound S70 according to the synthesis method of Example 77.TOF m / z: [M+Na]+: 3020.4. Example 86 - Synthesis of compound L-20 Caption: sodium ascorbate

[00239] Compound L-20 was synthesized from compound S63ecomposto Petition 870250075555, dated 08 / 26 / 2025, pp. 155 / 279 149 / 177 S70 according to the synthesis method of Example 77.TOF m / z: [M+Na]+: 3020.4. Example 87 - Synthesis of compound S76 Caption: piperidine Step 1: Resin loading

[00240] 3.7 g of 2-chlorotrityl chloride resin beads (1.05 mmol / g) were weighed and placed in a resin reactor and swollen in DMF for 1 hour. After swelling, the solvent was filtered, and a solution of (30 mL) of Fmoc-L-phenylalanine (1.5 g, 3.9 mmol, 1.0 eq.) and DIEA (1.3 mL, 7.7 mmol, 2.0 eq.) in DMF was added to the resin, and a resin reactor was stirred at room temperature for 4 hours. After filtration, the resin was blocked with MeOH / DlEA / DMF (5 mL / 2.5 mL / 25 mL) for 30 minutes, and then the resin was thoroughly washed with DMF (8 times) to provide compound S71. Step 2: Peptide chain extension

[00241] The resin was treated with piperidine / DMF (6 mL / 24 mL) twice, 20 minutes each time, and then thoroughly washed with DMF (8 times). A solution (30 mL) of Fmoc-glycyl-glycine (4.1 g, 11.6 mmol, 3.0 eq.), HATU (4.4 g, 11.6 mmol, 3.0 eq.), HOBt (1.6 g, 11.6 mmol, 3.0 eq.) and DIEA (3.4 mL, 19.4 mmol, 5.0 eq.) in DMF was added Petition 870250075555, dated 08 / 26 / 2025, pp. 156 / 279 150 / 177 nothing to the resin, and a resin reactor was stirred at room temperature for 2 hours. The resin was then washed with DMF (8 times) to provide compound S72.

[00242] The resin was treated with piperidine / DMF (6 mL / 24 mL) twice, 20 minutes each time, and then thoroughly washed with DMF (8 times). A solution (30 mL) of Fmoc-cysteic acid (4.5 g, 11.6 mmol, 3.0 eq.), HATU (4.4 g, 11.6 mmol, 3.0 eq.), HOBt (1.6 g, 11.6 mmol, 3.0 eq.) and DIEA (3.4 mL, 19.4 mmol, 5.0 eq.) in DMF was added to the resin, and a resin reactor was stirred at room temperature for 4 hours. The resin was then washed with DMF (8 times) to provide compound S73.

[00243] The resin was treated with piperidine / DMF (6 mL / 24 mL) twice, 20 minutes each time, and then thoroughly washed with DMF (8 times). A solution (30 mL) of compound S37 (4.1 g, 11.6 mmol, 3.0 eq.), HATU (4.4 g, 11.6 mmol, 3.0 eq.), HOBt (1.6 g, 11.6 mmol, 3.0 eq.) and DIEA (3.4 mL, 19.4 mmol, 5.0 eq.) in DMF was added to the resin, and a resin reactor was stirred at room temperature for 4 hours. The resin was then washed with DMF (8 times) to give compound S74.

[00244] The resin was treated with piperidine / DMF (6 mL / 24 mL) twice, 20 minutes each time, and then thoroughly washed with DMF (8 times). A solution (30 mL) of decomposed compounds S8 (4.6 g, 11.6 mmol, 3.0 eq.) and EEDQ (2.9 mL, 11.6 mmol, 3.0 eq.) in DMF was added to the resin, and a resin reactor was stirred at room temperature for 4 hours. The resin was then washed with DMF (8 times) to provide compound S75. Step 3: Resin cleavage

[00245] The resin was treated with an HFIP / CH2Cl2 solution (6 mL / 24 mL) for 30 minutes. The resin was filtered, the filtrate was concentrated under reduced pressure, and the crude product was purified by chromatography. Petition 870250075555, dated 08 / 26 / 2025, pp. 157 / 279 151 / 177 reversed-phase preparative column, and the preparation was lyophilized to provide compound S76 (white solid, 836 mg, 23%). LC-MS m / z (ES-): [M - H]-: 924.2. Example 88 - Synthesis of compound S77

[00246] In a 25 mL single-necked flask, compounds D-4 (50 mg, 0.069 mmol, 1.0 eq.), Fmoc-glycine (31 mg, 0.103 mmol, 1.5 eq.), HATU (39 mg, 0.103 mmol, 1.5 eq.), HOBt (14 mg, 0.103 mmol, 1.5 eq.) and dry DMF (3 mL) were added sequentially and dissolved uniformly, then DIEA (24 μL, 0.137 mmol, 2.0 eq.) was added dropwise under ice-cold water conditions, and the reaction was allowed to stand at room temperature. After 1 hour, HPLC showed that the reaction was complete. The reaction solution was purified by preparative reversed-phase column chromatography, and the preparation solution was lyophilized to provide compound S77 (white solid, 58 mg, 84%). LC-MS m / z (ES+): [M+H]+: 1009.2. Example 89 - Synthesis of compound S79

[00247] Compound S79 was synthesized from compound S77 and compound S76 according to the synthesis method of Example 26 and Example 27. LC-MS m / z (ES+): [M-100+2H]2+: 797.9 (response of the fragment ion of compound S79 after removal of the protecting group) Petition 870250075555, dated 08 / 26 / 2025, pp. 158 / 279 152 / 177 Boc and hydrogen ion addition). Example 90 - Synthesis of compound L-21

[00248] Compound L-21 was synthesized from compound S79 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+2H]2+: 769.8. Example 91 - Synthesis of compound S80

[00249] Compound S80 was synthesized from compound S76 and compound S30 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H]2+: 911.5. Example 92 - Synthesis of compound L-22

[00250] Compound L-22 was synthesized from compound S80 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+2H]2+: 833.4. Example 93 - Synthesis of compound S81

[00251] Compound S81 was synthesized from compound S76 and compound S33 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H]2+: 908.4. Example 94 - Synthesis of compound L-23 Petition 870250075555, dated 08 / 26 / 2025, pp. 159 / 279 153 / 177

[00252] Compound L-23 was synthesized from compound S81 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+2H]2+: 830.3. Example 95 - Synthesis of compound S82

[00253] Compound S82 was synthesized from compound S76 and compound S35 according to the synthesis method of Example 27. LC-MS m / z (ES+): [M+2H]2+: 908.3. Example 96 - Synthesis of compound L-24

[00254] Compound L-24 was synthesized from compound S82 according to the synthesis method of Example 28. LC-MS m / z (ES+): [M+2H]2+: 830.3. Example 97 - ADC-1 Preparation

[00255] ADC-1 was prepared using compound L-1 and anti-Trop2 antibody TR001 according to the method in general procedure A. Sequence information for TR001 is shown in Table 2. Petition 870250075555, dated 08 / 26 / 2025, pp. 160 / 279 154 / 177 Table 2: Description of the TR001 sequence Amino acid sequence of the light chain of TR001 DIQMTQSPSSLSASVGDRVTITCRASQDINKYLAWY QQKPGKVPKLLIYSTSTLQSGVPSRFSGSGSGTDF TLTISSLQPEDVATYYCLQYDDLFTFGQGTKLEIKRT VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Amino acid sequence of the heavy chain of TR001 QVQLVQSGAEVKKPGASVKLSCKASGYTFTSFDIN WVRQAPEQRLEWMGWIFPGDGNTKYSQKFQGRA TITRDTSASTAYMELSSLRSEDTAVYYCVRGEALYY FDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGG TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPG Example 98 - Preparation of ADC-2

[00256] ADC-2 was prepared using compound L-2 and the anticolor Petition 870250075555, dated 08 / 26 / 2025, pp. 161 / 279 155 / 177 po anti-Trop2 TR001 according to the method in the general procedure THE. Example 99 - Preparation of ADC-3

[00257] ADC-3 was prepared using compound L-1 and anti-Trop2 antibody TR002 according to the method in the general procedure. B. The sequence information for TR002 is shown in Table 3. Petition 870250075555, dated 08 / 26 / 2025, pp. 162 / 279 156 / 177 Table 3: Description of the TR002 sequence Amino acid sequence of the light chain of TR002 DIQMTQSPSSLSASVGDRVTITCRASQDINKYLA WYQQKPGKVPKLLIYSTSTLQSGVPSRFSGSGS GTDFTLTISSLQPEDVATYYCLQYDDLFTFGQGTK LEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNN FYPREAKVQWKVDNALQSGNSQESVTEQDSKDS TYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV CTKSFNRGEC Amino acid sequence of the heavy chain of TR002 QVQLVQSGAEVKKPGASVKLSCKASGYTFTSFDI NWVRQAPEQRLEWMGWIFPGDGNTKYSQKFQG RATITRDTSASTAYMELSSLRSEDTAVYYCVRGE ALYYFDYWGQGTLVTVSSASTKGPSVFPLAPSSK STSGGTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE DPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPG Example 100 - Preparation of ADC-4

[00258] ADC-4 was prepared using compound L-2 and anti-Trop2 antibody TR002 according to the method in general procedure B. Petition 870250075555, dated 08 / 26 / 2025, pp. 163 / 279 157 / 177 Example 101 - Preparation of ADC-5

[00259] ADC-5 was prepared using compound L-3 and anti-Trop2 antibody TR001 according to the method in general procedure A. Example 102 - Preparation of ADC-6

[00260] ADC-6 was prepared using compound L-7 and anti-Trop2 antibody TR001 according to the method in general procedure A. Petition 870250075555, dated 08 / 26 / 2025, pp. 164 / 279 158 / 177 Example 103 - Preparation of ADC-7

[00261] ADC-7 was prepared using compound L-8 and anti-Trop2 antibody TR001 according to the method in the general procedure. THE. Example 104 - ADC-8 Preparation

[00262] ADC-8 was prepared using compound L-9 and anti-Trop2 antibody TR001 according to the method in the general procedure. THE. Petition 870250075555, dated 08 / 26 / 2025, pp. 165 / 279 159 / 177 Example 105 - Preparation of ADC-9

[00263] ADC-9 was prepared using compound L-10 and anti-Trop2 antibody TR001 according to the method in general procedure A. Example 106 - Preparation of ADC-10

[00264] ADC-10 was prepared using compound L-11 and anti-Trop2 antibody TR001 according to the method in general procedure A. Petition 870250075555, dated 08 / 26 / 2025, pp. 166 / 279 160 / 177 Example 107 - Preparation of ADC-11

[00265] ADC-11 was prepared using compound L-1' and anti-Trop2 antibody TR001 according to the method in general procedure A. Example 108 - Preparation of ADC-12

[00266] ADC-12 was prepared using compound L-2' and anti-Trop2 antibody TR001 according to the method in general procedure A. Petition 870250075555, dated 08 / 26 / 2025, pp. 167 / 279 161 / 177 Example 109 - Preparation of ADC-13

[00267] ADC-13 was prepared using compound L-15 and anti-Trop2 antibody TR001 according to the method in general procedure C. Example 110 - Preparation of ADC-14

[00268] ADC-14 was prepared using compound L-16 and anti-Trop2 antibody TR001 according to the method in general procedure C. Petition 870250075555, dated 08 / 26 / 2025, pp. 168 / 279 162 / 177 Example 111 - Preparation of ADC-15

[00269] ADC-15 was prepared using compound L-17 and anti-Trop2 antibody TR001 according to the method in general procedure C. Example 112 - Preparation of ADC-16

[00270] ADC-16 was prepared using compound L-18 and anti-Trop2 antibody TR001 according to the method in general procedure C. Petition 870250075555, dated 08 / 26 / 2025, pp. 169 / 279 163 / 177 Example 113 - Preparation of ADC-17

[00271] ADC-17 was prepared using compound L-19 and anti-Trop2 antibody TR001 according to the method in general procedure C. Example 114 - Preparation of ADC-18

[00272] ADC-18 was prepared using compound L-20 and anti-Trop2 antibody TR001 according to the method in general procedure C. Petition 870250075555, dated 08 / 26 / 2025, pp. 170 / 279 164 / 177 Example 115 - Preparation of ADC-19

[00273] ADC-19 was prepared using compound L-8 and anti-Trop2 antibody TR001 according to the method in general procedure C. Example 116 - Preparation of ADC-20

[00274] ADC-20 was prepared using compound L-21 and anti-Trop2 antibody TR001 according to the method in general procedure C. Petition 870250075555, dated 08 / 26 / 2025, pp. 171 / 279 165 / 177 Example 117 - Preparation of ADC-21

[00275] ADC-21 was prepared using compound L-22 and anti-Trop2 antibody TR001 according to the method in general procedure C. Example 118 - Preparation of ADC-22

[00276] ADC-22 was prepared using compound L-23 and anti-Trop2 antibody TR001 according to the method in general procedure C. Petition 870250075555, dated 08 / 26 / 2025, pp. 172 / 279 166 / 177 Example 119 - Preparation of ADC-23

[00277] ADC-23 was prepared using compound L-24 and anti-Trop2 antibody TR001 according to the method in the general procedure. W. Example 120 - Determination of the drug-antibody relationship (DAR)

[00278] Reversed-phase high-performance liquid chromatography (RP-HPLC) to detect DAR RP-HPLC mobile phase preparation: Petition 870250075555, dated 08 / 26 / 2025, pp. 173 / 279 167 / 177

[00279] RP Mobile Phase A: 0.1% TFA in water; RP Mobile Phase B: 0.1% TFA in acetonitrile

[00280] The sample to be tested and the corresponding antibody control were diluted with sample diluent to 1 mg / mL; 2 μL of DTT raw material solution was added for each 98 μL of diluted sample, and a blank control of 98 μL of sample diluent + 2 μL of DTT raw material solution was prepared. Each sample was thoroughly mixed and then heated in a metal bath at 65 °C for 30 minutes. The processed samples were centrifuged at 14,000 rpm for 5 minutes or filtered with a 0.22 μm filter to remove larger particles from the samples. An inner cannula was placed in each sample vial, and the sample vials were then capped.

[00281] Sample vials filled with samples were placed on a sample plate, and the corresponding position, injection volume, number of injection needles, and injection method for each sample were defined according to the UPLC Standard Operating Procedures. The chromatographic column model was Proteomix RP-1000 (4.6*100mm, 5μm), Sepax.

[00282] The test wavelengths were 214 nm and 280 nm. The sample execution method was edited as follows: Time (min) Flow rate (mL / min) Percentage of volume of mobile phase A of RP (%): Percentage of volume of mobile phase B of RP (%): 0 0.5 75 25 3 0.5 75 25 28 0.5 50 50 30 0.5 5 95 32 0.5 5 95 33 0.5 75 25 40 0.5 75 25 Petition 870250075555, dated 08 / 26 / 2025, pp. 174 / 279 168 / 177 Table 4: Detailed DAR data for ligand-drug conjugates (ADCs) disclosed: Compound number Number of ADC prepared by conjugation DAR L-1 ADC-1 6.82 L-2 ADC-2 6.08 L-1 ADC-3 1.87 L-2 ADC-4 1.72 L-3 ADC-5 7.20 L-7 ADC-6 6.81 L-8 ADC-7 7.63 L-9 ADC-8 6.97 L-10 ADC-9 7.15 L-11 ADC-10 7.86 L-1' ADC-11 7.58 L-2' ADC-12 7.30 L-15 ADC-13 4.07 L-16 ADC-14 4.35 L-17 ADC-15 4.12 L-18 ADC-16 3.94 L-19 ADC-17 3.88 L-20 ADC-18 3.74 L-8 ADC-19 3.75 L-21 ADC-20 3.63 L-22 ADC-21 3.71 L-23 ADC-22 3.84 L-24 ADC-23 3.96 Example 121 - Evaluation of compounds for in vitro pharmacodynamic activity

[00283] In the present invention, several human-derived tumor cell lines (BxPC-3 (human orthotopic pancreatic adenocarcinoma cell), SW620 (human colon cancer cell), Petition 870250075555, dated 08 / 26 / 2025, pp. 175 / 279 169 / 177 H1975 (human lung adenocarcinoma cell), HCC827 (human lung adenocarcinoma cell), FaDu (human pharyngeal squamous cell carcinoma cell), and A431 (human epidermal carcinoma cells) were used as experimental models to evaluate the cytotoxicity of the compound on tumor cell lines. A certain number of tumor cells were seeded in a 96-well plate. After cell adhesion to the wall, gradient dilutions of the tested compounds were applied to the test cells, followed by incubation at 37°C and 5% CO2 for 5 days. Cell viability was measured by MTS, and the inhibitory effect of the control and test compounds on the tumor cell lines was evaluated by IC50. The compound with an initial concentration of 4000 nM was diluted 7 times, with a total of 8 concentration points.Finally, the survival rate was given by the equation: survival rate = (experimental group - blank) / (control - blank) χ 100%, and then the curve was fitted using the GraphPad Prism9 four-parameter model to calculate IC50. Table 5: In vitro pharmacodynamic activity of control compounds s and compounds s tested in human-derived tumor cell lines BxPC-3, SW620, and H1975: Compound BxPC-3 SW620 H1975 IC50(nM) D-4 (eribulin) 0.06 2.56 0.39 D-2 0.03 1.25 0.25 D-3 <0.005 <0.005 <0.005 D-7 <0.005 <0.005 0.01 D-8 <0.005 <0.005 <0.005 D-9 <0.005 <0.005 <0.005 D-10 0.02 0.2 0.13 D-11 0.01 0.15 0.06 D-12 <0.005 <0.005 <0.005 Petition 870250075555, dated 08 / 26 / 2025, pp. 176 / 279 170 / 177 Compound BxPC-3 SW620 H1975 IC50(nM) D-13 <0.005 <0.005 <0.005 D-14 0.01 0.19 0.1 D-15 0.03 0.69 0.14 D-21 0.05 0.24 0.24 Table 6: In vitro pharmacodynamic activity of control compounds s and the tested compounds s in human-derived tumor cell lines HCC827, FaDue A431: Compound HCC827 FaDu A431 IC50 (nM) D-4 (eribulin) 0.05 0.73 0.03 D-2 0.025 0.37 0.02 D-3 <0.005 <0.005 <0.005 D-7 <0.005 0.01 <0.005 D-8 <0.005 <0.005 <0.005 D-9 <0.005 <0.005 <0.005 D-10 0.01 0.16 0.03 D-11 0.01 0.08 0.02 D-12 <0.005 <0.005 <0.005 D-13 <0.005 <0.005 <0.005 D-14 0.01 0.16 0.01 D-15 0.02 0.33 0.02 D-21 0.04 0.39 0.12

[00284] The results are shown in the table above and in the FIGS. 1A-1F.

[00285] Conclusion: In BxPC-3, SW620, H1975, HCC827, FaDue A431 cell models, several compounds synthesized here had obvious antitumor effects, and compounds D-3, D-7, D-8, D-9, D-12, and D-13 showed the best effects. Example 122 - Evaluation of the stability of ADCs Petition 870250075555, dated 08 / 26 / 2025, pp. 177 / 279 171 / 177

[00286] ADCs were diluted with sterile human plasma to prepare samples with a drug concentration of 0.6 mg / ml and incubated in a water bath at 37°C for 0, 3, and 7 days, respectively. The samples incubated in plasma for 0, 3, and 7 days, and the control samples diluted in PBS with a final drug concentration of 0.6 mg / ml, were purified and extracted, respectively, to provide ADCs. Finally, the purified and extracted ADCs were appropriately tested to analyze their stability in plasma. Determination of monomer ratio using SEC-HPLC:

[00287] Chromatographic column: Biocore SEC-300 5μm, 4.6*300mm

[00288] Manufacturer: NanoChrom, Product code: B213-05003004630S

[00289] Mobile phase: 50 mM PB + 300 mM NaCl + 200 mM Arg + 5% IPA, pH = 6.5

[00290] The method parameters are listed below: Parameter Configuration Flow rate 0.3 mL / min Wavelength 280 nm Column temperature 30 °C Sample tray temperature Ambient temperature Sample load 20 µg Maximum pressure 150 bar / 15 MPa / 152.91 kg / cm² Gradient Isocratic Run time 20 min Petition 870250075555, dated 08 / 26 / 2025, pp. 178 / 279 Table 7: Evaluation of the stability of the tested ADCs of the invention in plasma: Day 0 Day 1 Day 5 Sample Aggregation % Monomer % Degradation Rate % RPDAR Aggregation % Monomer % Degradation Rate % RPDAR Aggregation % Monomer % Degradation Rate % RPDAR TR001 0.51 98.78 0.71 N / A 0.45 99.29 0.26 N / A 0.4 99.33 0.27 N / A ADC-13 9.62 88.81 1.58 4.07 5.83 93.34 0.83 3.88 5.28 93.72 1.00 3.80 ADC-14 4.78 93.91 1.31 4.35 4 .78 94 .54 0.69 4.19 4.28 94.89 0.83 4.02 ADC-15 7.50 91.02 1.48 4.12 6.47 92.39 1.14 3.73 5.81 92.91 1.27 3.51 ADC-16 4.94 94.56 0.50 3.94 4.79 94.45 0.76 4.15 4.61 94.52 0.87 4.06 ADC-17 6.41 92.88 0.71 3 .88 6 .46 92 .42 1 .12 4 .15 6 .29 92 .45 1 .26 3 .75 ADC-18 4 .44 95 .23 0 .33 3 .74 4 .21 95 .27 0 .52 3 .88 4 .07 95 .33 0 .59 3 .73 Conclusion: The results above show that the ADCs synthesized in the present invention exhibit good stability in human plasma. 172 / 177 Petition 870250075555, dated 08 / 26 / 2025, pages 179 / 279 173 / 177 Example 123 - In vitro pharmacodynamic activity test of ADCs in a single tumor model

[00291] In the present invention, several human-derived tumor cell lines (A431, HCC827, N87 (human gastric cancer cells), SW620, and FaDu) were used as experimental models to evaluate the in vitro pharmacodynamic activity of ADCs. A number of tumor cells were seeded in a 96-well plate, gradient dilutions of test antibodies and corresponding ADCs were applied to the cells, and they were treated for 5 days. Cell viability was detected using MTS, and the inhibitory effect of the test antibodies and ADCs on the tumor cell lines was assessed by IC50. The antibodies and ADCs, with an initial concentration of 500 nM, were diluted 7 times, totaling 8 concentration points, and treatment was carried out for 5 days. The final calculation was based on the equation: survival rate = (experimental group - blank) / (control - blank) x 100%, and then GraphPad Prism was used to fit the curve and calculate the CI50. Table 8: In vitro pharmacodynamic activity of ADCs tested in human-derived tumor cell lines A431, HCC827 and FaDu: No. A431 HCC827 FaDu IC50 (nM) TR001 >500 >500 >500 ADC-1 0 .013 0 .004 0 .091 ADC-2 0 .212 5 .365 - ADC-5 0 .033 0 .146 2 .542 ADC-13 0 .142 0.230 4.012 ADC-14 0.126 0.461 9.020 ADC-15 0.125 0.657 11.342 ADC-16 0.199 0.953 17.285 ADC-17 0.257 2.205 - ADC-18 0 .194 3 ,000 - Petition 870250075555, dated 08 / 26 / 2025, pp. 180 / 279 174 / 177 Table 9: In vitro pharmacodynamic activity of ADCs tested in human-derived N87 and SW620 tumor cell lines: No. N87 SW620 IC50(nM) TR001 >500 >500 ADC-1 0 .093 13 .417 ADC-5 1 .421 14 .724

[00292] The results are shown in the table above and in the FIGS. 2A-2E.

[00293] Conclusion: In the A431, HCC827, N87, SW620 and Fadu cell models, the nude anti-TR001 did not exhibit cytotoxic activity against tumor cells, and the ADCs synthesized according to the invention had an obvious antitumor effect. Example 124 - In vitro pharmacodynamic activity test of ADCs in a heterogeneous tumor model

[00294] In the present invention, heterogeneous tumor cell lines (A431+SW620) were used as experimental models to evaluate the in vitro pharmacodynamic activity of ADCs. A number of tumor cells were seeded in a 96-well plate, gradient dilutions of the tested ADCs were applied to the cells and treated for 5 days. Cell viability was detected using MTS, and the inhibitory effect of the test antibody and ADCs on the tumor cell lines was evaluated by IC50. The antibody and ADCs, with an initial concentration of 500 nM, were diluted 7 times, totaling 8 concentration points, and treatment was performed for 5 days. The final calculation was based on the equation: survival rate = (experimental group - blank) / (control - blank) x 100%, and then GraphPad Prism was used to fit the curve and calculate the IC50. Petition 870250075555, dated 08 / 26 / 2025, pp. 181 / 279 175 / 177 Table 10: In vitro pharmacodynamic activity of ADCs tested in heterogeneous A431+SW620 tumor cell lines: No. A431+SW620 IC50 (nM) ADC-19(control) 39,908 ADC-13 2,884 ADC-14 6,667 ADC-15 7,617 ADC-16 11,280

[00295] The results are shown in the table above and FIG. 3.

[00296] Conclusion: In the A431 + SW620 heterotumoral cell model, the ADCs synthesized according to the present invention showed a significant antitumor effect and were superior to the control ADC-19. Example 125 - In vivo pharmacodynamic activity test of ADCs

[00297] In the present invention, BALB / c-nu inoculated subcutaneously into a human-derived tumor cell line (A431) was used as an experimental model to evaluate the in vivo pharmacodynamics of ADCs. A suspension containing a certain number of tumor cells was inoculated subcutaneously into BALB / cnu. When the tumor volume reached approximately 180 mm3, the vehicle and ADC-5 were injected into the tail vein once a week for three times. Observation was continued. Tumor size and body weight were measured twice a week to assess the inhibitory effect of ADCs on tumor growth.

[00298] The results are shown in the table below. Petition 870250075555, dated 08 / 26 / 2025, pp. 182 / 279 Table 11: Efficacy of the tested ADC in the A431 mouse xenograft: Composite Mean tumor volume (mm3) T / C % TGI % D0 D3 D7 D10 D14 D17 White 175.01 456.78 828.16 1164 .44 1438.74 1671.07 100 0 ADC-5 (3 mg / Kg) 171.24 283.15 199.84 198.75 178.75 158.06 9 .67 90.33 T / C % = TRTV / CRTV x 100 %; TGI % = (1-T / C) x 100% Table 12: Effect of the tested ADC on the body weight of A431 transplanted mice: Compound D0 D3 D7 D10 D14 D17 Average body weight (g) Average body weight (g) BWC % Average body weight (g) BWC % Average body weight (g) BWC % Average body weight (g) BWC % Average body weight (g) BWC % White 20.45 22.09 8.06 23.11 13.05 23.28 13.86 24.40 19.35 24.19 18.33 ADC-5 (3 mg / Kg) 19.85 21.47 8.17 22.24 12.13 21.78 9.86 22.44 13.14 21.98 10.93 Conclusion: In mice transplanted with a single A431 tumor, the ADC synthesized according to the invention had significant antitumor effects. 176 / 177 Petition 870250075555, dated 08 / 26 / 2025, pp. 183 / 279 177 / 177

[00299] The above embodiments are used only to illustrate, but not to limit, the technical solutions of the invention. Any equivalent modification or substitution of the technical solutions of the invention without departing from the purpose and scope of the technical solutions of the invention shall fall within the scope of the invention.

Claims

1. A ligand-drug conjugate of formula I or a pharmaceutically acceptable solvate or salt thereof, Ab-(LD)n Formula I, characterized in that Ab is a ligand unit; L is a ligand for covalently connecting Ab to D; n is selected from integers or decimals between 1 and 40; wherein W is an oxygen atom or a sulfur atom, R1 and R2 are the same or different, and are each independently selected from: hydrogen atom, alkyl, alkoxy, alkenyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, -C(O)-Q1-Q2 and SO2-Q1-Q2, wherein Q1 is selected from the group consisting of O, N, S atoms and a chemical bond, Q2 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl and heteroaryl;Optionally, the alkyl, alkoxy, alkenyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, aryl and heteroaryl groups are each independently substituted by one or more substituents selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; or R1 and R2, together with a nitrogen atom connected thereto, form a heterocyclyl group of 3 to 8 members; Optionally, the heterocyclyl group is replaced by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms;R3 is selected from the group consisting of hydrogen, alkyl, acyl, sulfonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl atoms; optionally, the alkyl, acyl, sulfonyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups are each independently substituted by one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl atoms.

2. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to claim 1, characterized in that the Ab ligand unit is selected from the group consisting of an antibody, an antibody fragment or a protein; the antibody is preferably selected from the group consisting of a murine antibody, a rabbit antibody, a phage display-derived antibody, a yeast display-derived antibody, a chimeric antibody, a humanized antibody, a fully human antibody, an antibody fragment, a bispecific antibody and a multispecific antibody.

3. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to claim 1 or 2, characterized in that the antibody is a monoclonal antibody, selected, without limitation, from: anti-EGFRvIII antibody, anti-PD-1 antibody, anti-PD-L1 antibody, anti-DLL-3 antibody, anti-PSMA antibody, anti-CD70 antibody, anti-MUC16 antibody, anti-Petition 870250075555, dated 08 / 26 / 2025, page 1. 186 / 279 3 / 84 ENPP3, anti-TDGF1 antibody, anti-ETBR antibody, anti-MSLN antibody, anti-TIM-1 antibody, anti-LRRC15 antibody, anti-LIV-1 antibody, anti-CanAg / AFP antibody, anti-claudin 18.2 antibody, anti-Mesothelin antibody, anti-HER2(ErbB2) antibody, anti-EGFR antibody, anti-c-MET antibody, antibody anti-SLITRK6, anti-KIT / CD117 antibody, anti-STEAP1 antibody, anti-SLAMF7 / CS1 antibody, anti-NaPi2B / SLC34A2 antibody, anti-GPNMB antibody, antiHER3(ErbB3) antibody, anti-MUC1 / CD227 antibody, anti-AXL antibody, anti-CD166 antibody,anti-B7-H3(CD276) antibody, anti-PTK7 / CCK4 antibody, anti-PRLR antibody, anti-EFNA4 antibody, anti-5T4 antibody, anti-NOTCH3 antibody, anti-Nectin 4 antibody, anti-TROP-2 antibody, anti-CD142 antibody, anti-CA6 antibody, anti-GPR20 antibody, anti-CD174 antibody, anti-CD71 antibody, anti-EphA2 antibody, anti-LYPD3 antibody, anti-FGFR2 antibody, anti-FGFR3 antibody, anti-FRα antibody, anti-CEACAMs antibody, anti-GCC antibody, anti-Integrin Av antibody, anti-CAIX antibody, anti-Pcadherin antibody, anti-GD3 antibody, anti-Cadherin 6 antibody, anti-LAMP1 antibody, anti-FLT3 antibody, anti-BCMA antibody, antiCD79b, anti-CD19 antibody, anti-CD33 antibody, antiCD56 antibody, anti-CD74 antibody, anti-CD22 antibody, anti-CD30 antibody, anti-CD37 antibody, anti-CD47 antibody, anti-CD138 antibody, anti-CD352 antibody, anti-CD25 antibody or anti-CD123 antibody., 4. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to claim 1, characterized in that L has a structure shown in formula IV: O p Formula IV wherein, Petition 870250075555, dated 08 / 26 / 2025, page 187 / 279 4 / 84 M is a covalently bonding unit connected to Ab; Z is selected from the group consisting of -C1-C10 alkylene-, -C3-C8 carbocyclo-, -arylene-, 3- to 8-membered heterocyclyl-, -(CH2CH2O)r-, sulfonyl, amide, a chemical bond, Χ2 γ2 and any combinations thereof, wherein Xi and X2 are selected from the group consisting of -C1-C10 alkylene-, -C3-C8 carbocyclo-, -arylene-, 3- to 8-membered heterocyclyl-, (CH2CH2O)r-, -NR4-, carbonyl and any combinations thereof, wherein R4 is selected from the group consisting of hydrogen atom, deuterium atom, alkyl and substituted alkyl;Optionally, the 3- to 8-membered C1-C10 alkylene-, C3-C8 carbocyclo-, and heterocyclyl- groups are each independently substituted with one or more substituents selected from the group consisting of hydrogen atom, deuterium atom, halogen, hydroxyl, cyano, nitro, amino, alkyl, heteroalkyl, substituted alkyl, alkoxy, carboxy, and cycloalkyl; each heterocyclyl independently contains 1 to 3 atoms selected from the group consisting of N, O, and S; Y1 is a hydrophilic structure selected from the group consisting of carboxyl, phosphoric acid, polyphosphoric acid, phosphoric acid, sulfonic acid, sulfinic acid, polyethylene glycol (PEG), and any combinations thereof; Y2 is selected from the following structures: Petition 870250075555, dated 08 / 26 / 2025, p. 188 / 279 5 / 84 D 0 I 0 °Ϋ° ο , ο, οθ \ / e; r θ selected from integers between 1 and 10; qi and q2 are selected from integers between 1 and 8; and is selected from integers between 1 and 20;A is a peptide residue consisting of 2 to 7 amino acids; G is a spacer unit connected to D; ep is 0 or 1.

5. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to claim 4, characterized in that the linking unit M has a succinimide structure as represented by Formula a, or a structure as represented by Formula b or Formula c in which the ring in the succinimide group is in the open form: Formula a Formula b Formula c Formula a, Formula b or Formula c, a wavy line on the left indicates connection to a binding site at Ab, and a wavy line on the right indicates connection to a binding site at Z.

6. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to claim 4 or 5, characterized in that A is a polypeptide residue composed of 2 to 7 amino acids selected from the group consisting of phenylalanine, glycine, valine, lysine, citrulline, serine, glutamic acid, aspartic acid and cysteic acid.

7. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 4 to 6, characterized in that the spacer unit G is selected from the group consisting of structures represented by Formulas Va, Vb, Vc and Vd and any combinations thereof: R5R6R7 Formula Va Formula Vb Formula Vc Formula Vd wherein a wavy line on the left represents a binding site between an oxygen atom and peptide residue A, a wavy line on the right represents a binding site between an oxygen atom and drug D, and W is an oxygen atom or a sulfur atom and is a junction group between drug D and the spacer unit G; R5, R5', R6 and R7 are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl and substituted alkyl.

8. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 7, characterized in that the ligand-drug conjugate has a structure represented by Formula VI or Formula VII: Formula VI Petition 870250075555, dated 08 / 26 / 2025, page 190 / 279 7 / 84 Formula VII where, Ab, Z, A, R5, R6, R7, R3 and W are as defined in any one of claims 1 to 7; m, n2 and n3 are independently selected from integers or decimals between 0 and 40, ni, n2 and n3 are not 0 at the same time, and ni + n2 + n3 < 40.

9. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any of claims 4 to 8, characterized in that Z is selected from the group consisting of -C1-C10 alkylene-, -(CH2CH2O)r-, amide, NH2, and any combinations thereof; preferably, Z is -C2-alkylene or -C5-alkylene; preferably, Z is Xk yi, wherein, qi is selected. Petition 870250075555, dated 08 / 26 / 2025, p.191 / 279 8 / 84 of integers between 1 and 8; preferably, qi is 1; Preferably, q1 is 1, and -NH-X1-Y1 comprises the hydrophilic structural unit Aci, Aci is selected, without limitation, from the group consisting of (D / L) alanine, (D / L) leucine, (D / L) isoleucine, (D / L) valine, (D / L) phenylalanine, (D / L) proline, (D / L) tryptophan, (D / L) serine, (D / L) tyrosine, (D / L) cysteine, (D / L) cystine, (D / L) arginine, (D / L) histidine, (D / L) methionine, (D / L) asparagine, (D / L) glutamine, (D / L) threonine, (D / L) aspartic acid, (D / L) glutamic acid, derivatives of natural or non-natural amino acids and the following structures: preferably, q1 is 1, and -NH-X1-Y1 comprises the hydrophilic structural unit Aci, Aci is selected from the following structures: and H OH N.Preferably, Z is selected from integers between 1 and 8; preferably, q2 is 1; preferably, X2 is -(C1-C10 alkylene)-(CH2CH2O)r-(C=O)- or -(C1C10 alkylene)-(CH2CH2O)r-NR4-; preferably, q2 is 1, and -X2-Y2 comprises the hydrophilic structural unit Ac2, Ac2 is selected, without limitation, from Petition 870250075555, dated 08 / 26 / 2025, page 192 / 279 9 / 84 COOH OH J o ; r is selected from integers between 1 and 10 ; and is selected from integers between 1 and 0, I „OH P o J COOH j 20; preferably, q2 is 1, and -X2-Y2 makes up the hydrophilic structural unit Ac2, AC2 is selected from the following structures: HOOCD „ , , , 4 o Io LJ \ H 11 H11 cooh jo eo .

10. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 4 to 9, characterized in that A is a polypeptide residue composed of 2 to 5 amino acids selected from the group consisting of phenylalanine, glycine, valine, lysine, citrulline, serine, glutamic acid, aspartic acid and cysteic acid; preferably, A is a peptide residue formed by 2 to 4 amino acids selected from phenylalanine and glycine; more preferably, A is a tetrapeptide residue composed of glycine (G), glycine (G), phenylalanine (F) and glycine (G); and most preferably, A is -GGFG-.

11. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any of claims 1 to 10, characterized in that W is an oxygen atom or a sulfur atom, R1 and R2 are the same or different, and are each independently selected from the group consisting of: hydrogen atom, alkyl, alkoxy, alkenyl, cycloalkyl, -C(O)-Q1-Q2 and -SO2-Q1-Q2, wherein Q1 is selected from the group consisting of O and a chemical bond, and Q2 is selected from the group consisting of alkyl, heterocyclyl, alkenyl, aryl, heteroaryl and cycloalkyl; Optionally, the alkyl, heterocyclyl, alkenyl, aryl, heteroaryl, and cycloalkyl groups are each independently substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, halogen, deuterium, mercapto, amino, aryl, and hydroxy atoms;or R1 and R2 together with a nitrogen atom connected to it form a 3- to 6-membered heterocycline, and optionally the heterocycline is substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, hydroxyl, cycloalkyl and heterocycline atoms; R3 is selected from the group consisting of hydrogen and alkyl atoms, and optionally the alkyl is substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, hydroxyl, cycloalkyl and heterocycline atoms;Preferably, W is an oxygen atom, R1 and R2 are the same or different, and are each independently selected from the group consisting of: hydrogen atom, alkyl, alkenyl, haloalkyl, -C(O)-Q1-Q2 and -SO2-Q1-Q2, wherein Q1 is selected from the group consisting of O and a chemical bond, Q2 is selected from the group consisting of 3 to 8 membered alkyl, alkenyl, aryl and cycloalkyl, and optionally, the alkyl, alkenyl, aryl and cycloalkyl are each independently substituted with one or more substituents selected from the group consisting of hydrogen atom, alkyl, hydroxyl, halogen, aryl, and hydroxyl; or R1 and R2 together with a nitrogen atom connected to it form a 3- to 6-membered heterocycline containing one to two nitrogen atoms and optionally an oxygen atom;Optionally, the 3- to 6-membered heterocycline is substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, and haloalkyl atoms; R3 is selected from the group consisting of hydrogen and alkyl atoms, and the alkyl is substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, deuterium, amino, and hydroxyl atoms.

12. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 11, characterized in that W is an oxygen atom, R1 and R2 are the same or different, and are each independently selected from the group consisting of: hydrogen atom, C1-C4 alkyl (such as methyl, ethyl), C2-C4 alkenyl (such as allyl), C1-C4 haloalkyl (such as difluoroethyl) and the following structures: O O- Petition 870250075555, dated 08 / 26 / 2025, page.195 / 279 12 / 84 and or R1 and R2, together with a nitrogen atom connected thereto, form a 3- to 6-membered heterocyclyl containing one to two nitrogen atoms and optionally an oxygen atom (such as aziclopropyl, piperidinyl, piperazinyl, morpholinyl); optionally, the 3- to 6-membered heterocyclyl is substituted with one or more substituents selected from the group consisting of hydrogen atom, C1-C4 alkyl (e.g., methyl), and C1-C4 haloalkyl (e.g., trifluoromethyl); and R3 is selected from the group consisting of hydrogen atom and methyl.

13. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 7 to 12, characterized in that R5, R6 and R7 are each independently selected from the group consisting of hydrogen atom, deuterium atom, alkyl, haloalkyl, deuterated alkyl and hydroxyalkyl; and preferably, R5, R6 and R7 are simultaneously hydrogen atoms.

14. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula VIa or Formula VIIa: Petition 870250075555, dated 08 / 26 / 2025, page 196 / 279 13 / 84 Formula VIa Formula VIIa where, R1, R2, R3, n1, n2 and n3 are as defined in any one of claims 1 to 13.

15. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula VIb or Formula VIIb: Formula VIb where, R1, R2, R3, n1, n2 and n3 are defined as in any one of claims 1 to 13; Aci is a hydrophilic structural unit having the structure shown in formula d: ^'NH Formula d198 / 279 15 / 84 Xi and Yi are as defined in claim 4; preferably, Aci is selected, without limitation, from the group consisting of (D / L)alanine, (D / L)leucine, (D / L)isoleucine, (D / L)valine, (D / L)phenylalanine, (D / L)proline, (D / L)tryptophan, (D / L)serine, (D / L)tyrosine, (D / L)cysteine, (D / L)cystine, (D / L)arginine, (D / L)histidine, (D / L)methionine, (D / L)asparagine, (D / L)glutamine, (D / L)threonine, (D / L)aspartic acid, (D / L)glutamic acid, natural or non-natural amino acid derivatives and the following structures: and preferably, Aci is selected from the following structures: e.

16. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula Vic: Petition 870250075555, dated 08 / 26 / 2025, page 199 / 279 16 / 84 Formula Vic where Ri, R2, ni, Π2 and ri3 are defined in any one of claims 1 to 13.

17. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula Vld: Formula Vld wherein Ri, R2, ni, n2 and O3 are as defined in any one of claims 1 to 13.

18. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula VIe: Formula VIe wherein, Ri, R2, m, n2 and n3 are as defined in any of claims 1 to 13; Ac2 is a hydrophilic structural unit composed of -X2Y2, and X2 and Y2 are as defined in claim 4; preferably, Ac2 is selected, without limitation, from Petition 870250075555, dated 26 / 08 / 2025, p. 201 / 279 18 / 84 D ° °Ϋ° 0 ι H oe H o ; where r is selected from integers between 1 and 10; and is selected from integers between 1 and 20; preferably, AC2 is selected from the following structures: cooh , ο θo .

19. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula Vlf, wherein R1, R2, R1, O2 and O3 are as defined in any one of claims 1 to 13; Aci is a hydrophilic structural unit having the structure shown in formula d: ^'NH Formula d Petition 870250075555, dated 08 / 26 / 2025, page 202 / 279 19 / 84 Xi and Yi are as defined in claim 4; preferably, Aci is as defined in claim 15; Ac2 is a hydrophilic structural unit composed of -X2Y2, and X2 and Y2 are as defined in claim 4; Preferably, Ac2 is selected, without limitation, from .COOH , OH , o ; where r is selected from integers between 1 and 10; and is selected from integers enO .I „OH PO , COOH COOH , between 1 and 20; and preferably, Ac2 is selected from the following structures: cooh , o eo .

20. Ligand-drug conjugate or pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 13, characterized in that the ligand-drug conjugate has a structure represented by Formula VIg: Petition 870250075555, dated 08 / 26 / 2025, page 203 / 279 20 / 84 Formula VIg where, R1, R2, n1, n2 and n3 are as defined in any one of claims 1 to 13; Aci is a hydrophilic structural unit having the structure shown in formula d: ^'NH I Xk Yi Formula d Xi and Yi are as defined in claim 4; and preferably, Aci is as defined in claim i5. 2i. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 1a 20, characterized in that the ligand-drug conjugate is selected from the following structures: Petition 870250075555, dated 08 / 26 / 2025, p. 204 / 279 21 / 84 Petition 870250075555, dated 08 / 26 / 2025, p.205 / 279 22 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 206 / 279 23 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 207 / 279 24 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 208 / 279 25 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 209 / 279 26 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 210 / 279 27 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 211 / 279 28 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 212 / 279 29 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 213 / 279 30 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 214 / 279 31 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 215 / 279 32 / 84 COOH COOH HOOC NHOHNNHOHO MeO OH ' HOHHO COOH HO HNNNHOOO COOH COOH COOH HOOC HNNHOHNNHOO MeO OH - OHHO MeO OH ' NOH ' HHOOH' O MeO OH HO a H ' HOH COOH HO HNNNHOOO COOH MeO OH ' ' HOH MeO OH ' HO ' HHO . H Petition 870250075555, dated 08 / 26 / 2025, p. 216 / 279 33 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 217 / 279 34 / 84 Petition 870250075555, dated 08 / 26 / 2025, p.218 / 279 35 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 219 / 279 36 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 220 / 279 37 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 221 / 279 38 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 222 / 279 39 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 223 / 279 40 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 224 / 279 41 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 225 / 279 42 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 226 / 279 43 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 227 / 279 44 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 228 / 279 45 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 229 / 279 46 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 230 / 279 47 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 231 / 279 48 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 232 / 279 49 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 233 / 279 50 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 234 / 279 51 / 84 Petition 870250075555, dated 08 / 26 / 2025, p.235 / 279 52 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 236 / 279 53 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 237 / 279 54 / 84 wherein chiral carbons in positions 2 and 3 independently have R or S configuration; preferably, the chiral carbon in position 2 has S configuration, and the chiral carbon in position 3 has S configuration.

22. A ligand-drug conjugate or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 21, characterized in that the Ab ligand unit is an antibody, the antibody being an anti-TROP-2 antibody; preferably, the antibody consists of heavy chains and light chains, the light chains comprising CDR-L1, CDR-L2 and CDR-L3 having amino acid sequences established at SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3; preferably, the heavy chains comprise CDRH1, CDR-H2 and CDR-H3 having amino acid sequences established at SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6; Preferably, the light chain comprises a variable light chain region having an amino acid sequence of SEQ ID NO: 7; more preferably, the light chain further comprises a constant light chain region having an amino acid sequence of SEQ ID NO: 8;Preferably, the amino acid sequence of the light chain is SEQ ID NO: 9; preferably, the light chain comprises a variable light chain region having an amino acid sequence of SEQ ID NO: 10; more preferably, the light chain further comprises a constant light chain region having an amino acid sequence of SEQ ID NO: 11; preferably, the amino acid sequence of the light chain is SEQ ID NO: 12; preferably, the heavy chain comprises a variable heavy chain region having an amino acid sequence of SEQ ID NO: 13; more preferably, the heavy chain further comprises a constant heavy chain region having an amino acid sequence of SEQ ID NO: 14; preferably, the amino acid sequence of the heavy chain is SEQ ID NO:

15.

23. A ligand-drug conjugate of formula VIII or formula IX, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof, Petition 870250075555, dated 08 / 26 / 2025, pp. 239 / 279 56 / 84, characterized in that Mi is a ligand unit, and Z, p, A, G, W, Ri, R2 and R3 are as defined in any one of claims 1 to 13.

24. A drug-ligand conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23, characterized in that the drug-ligand conjugate has a structure represented by Formula VIII-1 or Formula IX-1: Petition 870250075555, dated 08 / 26 / 2025, p. 240 / 279 57 / 84 Formula IX-1 where Z, A, R1, R2, R3, R5, R6 and R7 are as defined in any of claims 1 to 13.

25. A drug-ligand conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the drug-ligand conjugate has a structure represented by Formula Villa or Formula IXa: Formula VIIIa Formula IXa wherein R1, R2 and R3 are as defined in any of claims 1 to 13.

26. A drug-ligand conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the drug-ligand conjugate has a structure represented by Formula VIIIb or Formula IXb: Formula VIIIb Formula IXb wherein, R1, R2 and R3 are as defined in any of claims 1 to 13; Aci is a hydrophilic structural unit having the structure shown in formula d: ^'NH Formula d Xi and Y1 are as defined in claim 4; preferably, Aci is as defined in claim 15. Petition 870250075555, dated 26 / 08 / 2025, p. 242 / 279 59 / 84 27. A ligand-drug conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the ligand-drug conjugate has a structure represented by Formula VIIIc: VIIIc wherein R1 and R2 are as defined in any one of claims 1 to 13.

28. A drug-ligand conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the drug-ligand conjugate has a structure represented by Formula VIIId: VIIId wherein R1 and R2 are as defined in any of claims 1 to 13. Petition 870250075555, dated 08 / 26 / 2025, p. 243 / 279 60 / 84 29. Ligand-drug conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the ligand-drug conjugate has a structure represented by Formula VIIIe: Formula VIIIe wherein, Ri and R2 are as defined in any of claims 1 to 13; Ac2 is a hydrophilic structural unit composed of -X2Y2, X2 and Y2 are as defined in claim 4; preferably, Ac2 is as defined in claim 9 or 18.

30. A ligand-drug conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the ligand-drug conjugate has a structure represented by Formula VIIIf: Petition 870250075555, dated 08 / 26 / 2025, p. 244 / 279 61 / 84 Formula Vlllf wherein, R1 and R2 are as defined in any of claims 1 to 13; Aci is a hydrophilic structural unit composed of -XiYi, and Xi and Yi are as defined in claim 4; preferably, Aci is as defined in claim i5; Ac2 is a hydrophilic structural unit composed of -X2Y2, and X2 and Y2 are as defined in claim 4; Preferably, Ac2 is as defined in claim 9 or i8. 3i.A ligand-drug conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to claim 23 or 24, characterized in that the ligand-drug conjugate has a structure represented by Formula VIIg: Formula VIIIg wherein, R1 and R2 are as defined in any of claims 1a i3; Aci is a hydrophilic structural unit composed of -XiYi, and Xi and Yi are as defined in claim 4; preferably, Aci is as defined in claim 5.

32. A ligand-drug conjugate, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof according to any of claims 23 to 3i, characterized in that the ligand-drug conjugate is selected from the following structures: [Petition 870250075555, dated 26 / 08 / 2025, p. 245 / 279 62 / 84] 247 / 279 64 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 248 / 279 65 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 249 / 279 66 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 250 / 279 67 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 251 / 279 68 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 252 / 279 69 / 84 Petition 870250075555, dated 08 / 26 / 2025, p. 253 / 279 70 / 84 O HO-A , PO HO Petition 870250075555, dated 08 / 26 / 2025, p. 254 / 279 71 / 84 Petition 870250075555, dated 08 / 26 / 2025, p.255 / 279 72 / 84 Petition 870250075555, dated 08 / 26 / 2025, pg. 256 / 279 73 / 84 Petition 870250075555, dated 08 / 26 / 2025, pg. 257 / 279 74 / 84 Petition 870250075555, dated 08 / 26 / 2025, pg. 258 / 279 75 / 84 wherein chiral carbons in positions 2 and 3 independently have R or S configuration; preferably, the chiral carbon in position 2 has S configuration, and the chiral carbon in position 3 has S configuration.

33. Compound of formula X, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or a pharmaceutically acceptable solvate or salt thereof, Formula X characterized in that W is an oxygen atom or a sulfur atom, and preferably, W is an oxygen atom; R1 and R8 are each independently selected from the group consisting of: hydrogen atom, alkyl, acyl, sulfonyl, cycloal Petition 870250075555, dated 08 / 26 / 2025, page 259 / 279 76 / 84 chyla, heterocyclyl, aryl and heteroaryl, and are not simultaneously hydrogen; Optionally, the alkyl, acyl, sulfonyl, cycloalkyl, aryl, and heteroaryl groups are each independently substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxy, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms; preferably, R1 is alkyl, and R8 is H;R2 is -C(O)-Q1-Q2 or -SO2-Q1-Q2, where Q1 is selected from the group consisting of O, N and S atoms and a chemical bond; in a case where Q1 is selected from the group consisting of O, N and S atoms, Q2 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl and heteroaryl, and optionally the alkyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl and heteroaryl are each independently substituted with one or more substituents selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxy, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; In a case where Q1 is a chemical bond, Q2 is selected from the group consisting of alkyl, benzyl, cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl, and heteroaryl;In a case where Q2 is an alkyl group, the alkyl group is substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, cyano, azido, nitro, carboxyl, acyl, carbonyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl atoms;In a case where Q2 is selected from the group consisting of cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, alkenyl, aryl and heteroaryl, the cycloalkyl, heterocyclyl, spirocyclyl, bridging ring, Petition 870250075555, dated 08 / 26 / 2025, page. 260 / 279 77 / 84 ponte, alkenyl, aryl and heteroaryl are each independently substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, deuterium, amino, cyano, hydroxy, mercapto, azido, nitro, carboxyl, acyl, carbonyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl atoms, and in a case where Q2 is a cycloalkyl with the substituent being a hydroxyl, an amino or a mercapto, the substituent is in any position except a carbon atom connected to -C(O)-.; 34. Compound of formula X, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to claim 33, characterized in that the compound is a compound of formula XIa or formula XIb, or an isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, MeO Formula XIa Formula XIb wherein Ri is an alkyl, and preferably Ri is a methyl, Q1 is an O atom or a chemical bond; in a case where Q1 is an O atom, Q2 is selected from the group consisting of alkyl, cycloalkyl, alkenyl and aryl, and optionally the alkyl, cycloalkyl, alkenyl and aryl are each independently substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxy, hydroxyalkyl and aryl atoms;In a case where Q1 is a chemical bond, Q2 is selected from the group consisting of alkyl, benzyl, cycloalkyl, alkenyl and aryl; in a case where Q2 is an alkyl, the alkyl is substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, deuterium, azide, nitro and aryl atoms; and in a case where Q2 is selected from the group consisting of cycloalkyl, alkenyl and aryl, the cycloalkyl, alkenyl and aryl are each independently substituted with one or more substituents selected from the group consisting of hydrogen, alkyl, halogen, hydroxyl, hydroxyalkyl and aryl atoms, and in a case where Q2 is a cycloalkyl with the substituent being a hydroxyl, an amino or a mercapto, the substituent is in any position except a carbon atom connected to -C(O)-.; 35. Compound of formula X, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to claim 33 or 34, characterized in that the compound is selected from the following structures: Petition 870250075555, dated 08 / 26 / 2025, pp. 262 / 279 79 / 84 Petition 870250075555, dated 08 / 26 / 2025, pp. 263 / 279 80 / 84 36. Use of the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 23 to 32, or the compound or the isomer, mesomer, racemate or enantiomer of the same or a mixture thereof or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 33 to 35, characterized in that it is an intermediate for the preparation of a drug-ligand conjugate, and the drug-ligand conjugate is as defined in any one of claims 1 to 22.

37. A drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 1 to 22, or the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 23 to 32, or the compound, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof according to any one of claims 33 to 35, characterized in that: the pharmaceutically acceptable salts include sodium, potassium, calcium or magnesium salts formed by acidic functional groups in the structural formula and acetates, trifluoroacetates, citrates, oxalates, tartrates, malates, nitrates, chlorides, bromides, iodides, sulfates, bisulfates, phosphates, lactates, oleates, ascorbates, salicylates, formates, glutamates, methanesulfonates,Ethane sulfonates, benzene sulfonates, or p-toluene sulfonates formed by basic functional groups in their structure.

38. Pharmaceutical composition, characterized in that it comprises the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof as defined in any of claims 1 to 22, or the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or the mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any of claims 23 to 32, Petition 870250075555, dated 08 / 26 / 2025, pp. 265 / 279 82 / 84 or the compound, or the isomer, mesomer, racemate or enantiomer thereof, or the mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any of claims 33 to 35, and optionally further comprising a pharmaceutically acceptable carrier.

39. Pharmaceutical formulation, characterized in that it comprises the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 1 to 22, or the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or the mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 23 to 32, or the compound, or the isomer, mesomer, racemate or enantiomer thereof, or the mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 33 to 35.

40. Use of the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 1 to 22, or the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or the mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 23 to 32, or the compound, or the isomer, mesomer, racemate or enantiomer thereof, or the mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 33 to 35, characterized in that it is in the preparation of a medicament for the treatment or prevention of a cancer or tumor; preferably, the cancer or tumor is a solid tumor or a hematological tumor; Preferably, the cancer or tumor is selected from Petition 870250075555, dated 08 / 26 / 2025, page 1.266 / 279 83 / 84 neocarcinoma, ovarian cancer, cervical cancer, uterine cancer, prostate cancer, kidney cancer, urinary tract cancer, bladder cancer, liver cancer, stomach cancer, endometrial cancer, salivary gland cancer, esophageal cancer, lung cancer, colon cancer, rectal cancer, colorectal cancer, bone cancer, skin cancer, thyroid cancer, pancreatic cancer, melanoma, glioma, neuroblastoma, glioblastoma multiforme, sarcoma, lymphoma, leukemia and hypopharyngeal cancer.

41. A method for preventing or treating a cancer or tumor, characterized in that it comprises administering to an individual in need thereof a prophylactic or therapeutically effective amount of the drug-ligand conjugate or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 1 to 22, or the drug-ligand conjugate, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 23 to 32, or the compound, or the isomer, mesomer, racemate or enantiomer thereof, or a mixture thereof, or the pharmaceutically acceptable solvate or salt thereof as defined in any one of claims 33 to 35; preferably, the cancer or tumor is a solid tumor or a hematological tumor;Preferably, the cancer or tumor is selected from adenocarcinoma, ovarian cancer, cervical cancer, uterine cancer, prostate cancer, renal cancer, urinary tract cancer, bladder cancer, liver cancer, stomach cancer, endometrial cancer, salivary gland cancer, esophageal cancer, lung cancer, colon cancer, rectal cancer, colorectal cancer, bone cancer, skin cancer, thyroid cancer, pancreatic cancer, melanoma, glioma, neuroblastoma, glioblastoma multiforme, sarcoma, lymphoma, leukemia, and hypopharyngeal cancer.

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