Conjugation of Cytotoxic Agents by Screw Connection

Abstract

Bis-linked (double-linked) conjugates of cytotoxic agents and cell-binding molecules are provided. Bis-linking methods for producing conjugates of cell-binding agents and cytotoxic agent molecules in a specific manner are provided. Applications of the conjugates for the treatment of cancer, autoimmune diseases, or infectious diseases are also provided. The present invention provides a bis-linked compound of formula (I). JPEG2023061938000454.jpg37116

Claims

**Claim 1**: A method for producing a conjugate compound of formula (I) by reacting two or more residues of a cell-binding agent / molecule with a reactive bis-linker compound of formula (II) simultaneously or sequentially: 【Chemical 1】 【Chemical Formula 10】 Wherein: 【Chemical 11】 represents a single bond; 【Chemical 12】 is optionally either a single bond, double bond, or triple bond, or may optionally not be present; 【Chemical 13】 When representing a triple bond, Lv １ and Lv ２ both do not exist; n and m1 are independently 1 to 20; The cell-binding agent / molecule is an antibody, single-chain antibody; an antibody fragment that binds to a target cell; a monoclonal antibody; a single-chain monoclonal antibody; or a monoclonal antibody fragment that binds to a target cell; a chimeric antibody; a chimeric antibody fragment that binds to a target cell; a domain antibody; a domain antibody cross-section that binds to a target cell; an adnectin mimicking an antibody; or DARPins; The cytotoxic or functional molecule within the parentheses is a drug / molecule / drug for treatment; or a protein / molecule for immunotherapy; or a cell surface receptor-binding ligand; or a functional molecule for enhancing binding or stabilizing the cell-binding agent; a chemotherapeutic compound, antibody or antibody fragment; or an siRNA or DNA molecule; or a tubulysin, calicheamicin, auristatin, maytansinoid, CC-1065 analog, morpholinodoxorubicin, taxane, cryptophycin, amatoxin, epothilone, eribulin, geldanamycin, duocarmycin, daunomycin, methotrexate, vindesine, vincristine, and benzodiazepine dimer (including dimers of pyrrolobenzodiazepine (PBD), tomamycin, indolinobenzodiazepine, imidazobenzothiadiazepine, or oxazolidinobenzodiazepine) containing therapeutic agents; X and Y independently represent functional groups that are the same or different and are linked to the cytotoxic drug via a peptide, ester, carbamate, carbonate, or amide bond; Z1 and Z2 are independently functional groups that are the same or different and bind to the cell-binding agent / molecule to form a disulfide bond; L1 and L2 are independently the same or different, C1-C8 alkyl; C2-C8 heteroalkyl, peptide, alkylcarbonyl; 1 to 8 amino acids; or polyethyleneoxy having the formula (OCH2CH2)p or (OCH2-CH(CH3))p, wherein p is an integer from 0 to about 500, or a combination thereof; Alternatively, L1 and L2 independently have a non-self-destructive linker component containing one of the following structures: 【Chemical Formula 5】 Wherein the atom labeled with (*) is a binding point with an additional spacer or releasable linker unit, a cytotoxic agent, and / or a cell adhesion molecule (CBA); the definitions of X1, Y1, U1, R5, and R5' are as described above; r is 0 to 100; m and n are each independently 0 to 6; Furthermore, the L1 or L2 can be independently composed of one or more of the following components: 【Chemical Formula 6】 【Chem.】 And an L- or D-, natural or unnatural peptide containing 1 to 20 amino acids; Wherein The bond in the center of the carbon atom bond means that it can bond with either of the adjacent carbon atoms; the wavy line is the place where it can be connected within another bond; Alternatively, X, Y, L1, L2, Z1, or Z2 may not exist independently, but L1 and Z1, or L2 and Z2, or L1 and X, or L2 and Y cannot exist simultaneously, The conjugate of the formula (I) particularly excludes the following structures: 【Chemical Formula 9】 Wherein n = 1 to 30; m'' = 1 to 3; R''' = H, CH3, or C2H5. Lv １ and Lv ２ represent a leaving group that can react with the thiol group of the same or different cell binding agent / molecule; R １ is H, C １ -C ８ alkyl, C ２ -C ８ alkenyl, heteroalkyl, alkylcycloalkyl, or heterocycloalkyl; C ３ -C ８ aryl, Ar-alkyl, heterocycle, carbocycle, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl, or heteroallyl, or C ２ -C ８ ester, ether, or amide; or a peptide containing 1 to 8 amino acids; or a polyethyleneoxy unit having the formula (OCH ２ CH ２ ) ｐ or (OCH ２ CH(CH ３ )) ｐ where p is an integer from 0 to about 5000, or a combination thereof, The compound of the formula (II) particularly excludes the following structures: 【Chemical Formula 15】 wherein, m'' = 1 to 3; R''' = H, CH ３ , or C ２ H ５ is as follows. **Claim 2**: A method for producing a conjugate compound, comprising reacting two or more functional groups of a cytotoxic or functional molecule with a reactive bis-linker compound of the following formula (III) simultaneously or sequentially to obtain the conjugate compound of the formula (I) according to claim 1: 【Chemical 16】 Wherein m １ , n, 【Chemical 17】 , cell-binding agent / molecule, L １ , L ２ , Z1, and Z ２ are defined the same as in claim 1; X' and Y' are functional groups that can react independently with the residues of a cytotoxic or functional molecule simultaneously or sequentially to form X and Y respectively, wherein X and Y are defined in formula (I). **Claim 3**: A method for producing a conjugate compound, comprising reacting a cytotoxic or functional molecule and a cell-binding agent / molecule with a reactive bis-linker compound of the following formula (IV) independently, or simultaneously, or sequentially to obtain the conjugate compound of the formula (I) according to claim 1: 【Chemical Formula 19】 Wherein 【Chemical 20】 , m １ , L １ , L ２ , Lv1, Lv2, Z １ , and Z ２ have the same definitions as in claim 1; X' and Y' have the same definitions as in claim 2, The compound of the formula (IV) particularly excludes the following structures: 【Chemical 21】 Wherein m'' = 1 to 3. **Claim 4** The method according to any one of claims 1 to 3, wherein the conjugate compound of formula (I) has a structure represented by the following formula (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g), (I-h), (I-i), (I-j), (I-p), (I-q), (I-r), (I-s), (I-t), or (I-u): 【Chemical 22】 【Chem.】 【Chem.】 Wherein, X ７ and Y ７ are independently CH, CH ２ , NH, O, S, NHNH, N(R １ ), and N; a chemical bond connecting S in the middle of two carbon atoms means that it can connect either of the two adjacent carbon atoms; 【Chemical 23】 , X, Y, R １ , n, L １ , and L ２ has the same definition as in claim 1; the cytotoxic and / or functional molecule is the same as the cytotoxic and / or functional molecule described in claim 1.

5. The method according to claim 1, wherein the compound of formula (II) has a structure represented by formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (II-h), (II-i), (II-j), (II-k), (II-l), (II-t), (II-u), (II-v), (II-w), (II-x), (II-y), (II-z), or (II-a1): 【Chemical 24】 [Chemical] Wherein, X ７ and Y ７ are independently CH, CH ２ , NH, O, S, NHNH, N(R １ ), and N; the chemical bond connecting to Br in the middle of two carbon atoms means that it can connect either of the two adjacent carbon atoms; 【Chemical 25】 , cytotoxic / or functional molecule, R １ , X, Y, L １ , L ２ , Lv １ , and Lv ２ are defined the same as in claims 1 and 2.

6. The method according to claim 2, wherein the compound of formula (III) has a structure represented by the following formula (III-a), (III-b), (III-c), (III-d), (III-e), (III-f), (III-g), (III-h), (III-i), (III-j), (III-p), (III-q), (III-r), (III-s), (III-t), or (III-u): 【Chemical 26】 【Chem.】 【Chem.】 Wherein, X ７ and Y ７ are independently CH, CH ２ , NH, O, S, NHNH, N(R １ ), and N; a chemical bond connecting S located between two carbon atoms means that it can connect either of the two adjacent carbon atoms; R １ , X', Y', n, L １ , and L ２ have the same definitions as in claims 1 and 2.

7. The method according to claim 3, wherein the compound of formula (IV) has a structure represented by the following formula (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-i), (IV-j), (IV-k), (IV-l), (IV-t), (IV-u), (IV-v), (IV-w), (IV-x), (IV-y), (IV-z), or (IV-a1): 【Chemical 27】 Wherein, X ７ and Y ７ are independently CH, CH ２ , NH, O, S, NHNH, N(R １ ), and N; 【Chemical 28】 , R １ , X', Y', n, L １ , and L ２ have the same definitions as in claims 1 and 2.

8. The method according to any one of claims 1 to 3, wherein the cytotoxic or functional molecule is selected from the following: (1) A chemotherapeutic agent selected from the group consisting of the following: a) An alkylating agent selected from the following group: nitrogen mustards: chlorambucil, chloronaphazine, cyclophosphamide, dacarbazine, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, mannomustine, mitobronitol, melphalan, mitolactol, pipobroman, nobenbiotin, phenesterine, prednimustine, thiotepa, trofosfamide, uracil mustard; CC-1065 and adozelesin, carzelesin, bizelesin, or synthetic analogs thereof; duocarmycin and synthetic analogs thereof, KW-2189, CBI-TMI, or CBI dimers; benzodiazepine dimers or (pyrrolobenzodiazepine (PBD) dimers, tomatimycin dimers, indolinobenzodiazepine dimers, imidazobenzothiadiazepine dimers, or oxazolidinobenzodiazepine dimers; nitrosourea compounds including carmustine, lomustine, chloroozotocin, fotemustine, nimustine, ranimustine; alkyl sulfonates including busulfan, treosulfan, improsulfan, and piposulfan; triazenes or dacarbazine; platinum-containing compounds including carboplatin, cisplatin, oxaliplatin; aziridines, benzodopa, carboquone, metsuredopa, or uredopa; ethyleneimines, and methylmelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide, and trimethylolmelamine; b) Plant alkaloids selected from the following group: vinca alkaloids including vincristine, vinblastine, vindesine, vinorelbine, navelbine; taxoids including paclitaxel, docetaxel, and analogs thereof; maytansinoids including DM1, DM2, DM3, DM4, DM5, DM6, DM7, maytansine, ansamitocin, and analogs thereof; cryptophycins (including the group consisting of cryptophycin 1 and cryptophycin 8); epothilones, erythrobins, discodermolide, bryostatins, drostatins, auristatins, tubulysins, cephalostatins; pancratistatin; sarcodictyin; spongistatin; c) A DNA topoisomerase inhibitor selected from the following group: 9-aminocamptothecin, camptothecin, crisnatol, daunomycin, etoposide, etoposide phosphate, irinotecan, mitoxantrone, novantrone, retinoic acid (or retinols), teniposide, topotecan, 9-nitrocamptothecin, or epipodophyllins including RFS 2000; or mitomycins and their analogs; d) An antimetabolite selected from the following group: {[Antifolates: (methotrexate, trimethoprim, denopterin, pteropterin, aminopterin (4-aminopteroic acid), or a DHFR inhibitor including folic acid analogs); IMP dehydrogenase inhibitors (including mycophenolic acid, thiazofurin, ribavirin, EICAR); ribonucleotide reductase inhibitors (including hydroxyurea, deferoxamine)]; [Pyrimidine analogs: Uracil analogs: (including ancitabine, azacitidine, 6-azauridine, capecitabine (Xeloda), carmofur, cytarabine, didoxuridine, doxifluridine, enocitabine, 5-fluorouracil, floxuridine, raltitrexed (Tomudex)); Cytosine analogs: (including cytarabine, cytosine arabinoside, fludarabine); Purine analogs: (including azathioprine, fludarabine, mercaptopurine, thiampurine, thioguanine)]; Folic acid supplements, folinic acid}; e) A hormonal therapy agent selected from the following group: {Receptor antagonists: [Anti-estrogens: (including megestrol, raloxifene, tamoxifen); LHRH agonists: (including goserelin, leuprolide acetate); Anti-androgens: (including bicalutamide, flutamide, castasterone, drostanolone propionate, epitostanol, goserelin, leuprolide, mepitiostane, nilutamide, testolactone, trilostane, and other androgen inhibitors)]; Retinoids / deltoid muscles: [Vitamin D3 analogs: (including CB1093, EB1089, KH1060, cholecalciferol, ergocalciferol); Photodynamic therapy agents: (including verteporfin, phthalocyanine, photosensitizer Pc4, demethoxy-hypocrellin A); Cytokines: (including interferon α, interferon γ, tumor necrosis factor (TNF), TNF domain-containing human proteins)]}; f) A kinase inhibitor selected from the following group: BIBW2992 (anti-EGFR / Erb2), imatinib, gefitinib, pegaptanib, sorafenib, dasatinib, sunitinib, erlotinib, nilotinib, lapatinib, axitinib, pazopanib, vandetanib, E7080 (anti-VEGFR2), mubritinib, ponatinib (AP24534), bafetinib (INNO-406), bosutinib (SKI-606), cabozantinib, visimodegib, iniparib, luxolitinib, CYT387, axitinib, tibosutinib, sorafenib, bevacizumab, cetuximab, trastuzumab, ranibizumab, panitumumab, ispinesib; g) A poly(ADP-ribose) polymerase (PARP) inhibitor selected from the group consisting of olaparib, niraparib, iniparib, talazoparib, veliparib, CEP9722 (Cephalon), E7016 (Eisai), BGB-290 (BeiGene), or 3-aminobenzamide; h) An antibiotic selected from the following group: enediyne antibiotics (selected from the group consisting of calicheamicins, calicheamicin γ1, δ1, α1 and β1; dynemicin including dynemicin A and deoxydynemicin; esperamicin, kedarcidin, C-1027, mazlopeptin, and neocarzinostatin chromophore and related pigment protein enediyne antibiotic chromophores), actinomycins, actinomycin, anthramycin, azaserine, bleomycins, cactinomycin, carabicin, calminomycin, cardinophilin; chromomycins, daunorubicin, daunomycin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin, morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, queramycin, rhodomycin, streptozocin, streptozocin, tubercidin, ubenimex, dinostatin, zorubicin; i) Polyketides (acetogenins), bullatacin and bullatacinone; gemcitabine, epoxomicins (including carfilzomib), bortezomib, thalidomide, lenalidomide, pomalidomide, tosedostat, zibotentan, PLX4032, STA-9090, Stimuvax, allovectin-7, zygeba, probenecid, erbitux, isoprenylation inhibitors and lovastatin, dopaminergic neurotoxins and 1-methyl-4-phenylpyridinium ion, cell cycle inhibitors (selected from staurosporine), actinomycins (including the group consisting of actinomycin D, dactinomycin), bleomycins (including the group consisting of bleomycin A2, bleomycin B2, peplomycin), anthracyclines (including the group consisting of daunorubicin, doxorubicin (adriamycin), idarubicin, epirubicin, pirarubicin, zorubicin.), mitoxantrone, MDR inhibitors or verapamil, Ca ２＋ An ATP inhibitor or thapsigargin, a histone deacetylase inhibitor (including the group consisting of vorinostat, romidepsin, panobinostat, valproic acid, mocetinostat (MGCD0103), belinostat, PCI-24781, entinostat, SB939, resminostat, givinostat, AR-42, CUDC-101, sulforaphane, trichostatin A); thapsigargin, celecoxib, glitazones, epigallocatechin gallate, disulfiram, salinosporamide A, anti-adrenal drugs (including the group consisting of aminoglutethimide, mitotane, trilostane); aceglatone; aldophosphamide cricoside; aminolevulinic acid; amsacrine; arabinoside, bestrabucil; bisantrene; edatrexate; defofamine, demeclocycline, diazicon, difluoromethylornithine (DFMO), elfomycin; ellipticine acetate, etoclucid; gallium nitrate; gacitosine; hydroxyurea; ibandronate, lentinan; lonidamine; mitoguazone; mitoxantrone; mopidamol; nitraerine; pentostatin; phenamet; pirarubicin; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK (registered trademark); razoxane; lysocine; schizophyllan; spirogermanium; tenuazonic acid; triazicon; 2,2',2''-trichloroethylamine; trichothecenes (including the group consisting of T2 toxin, verrucarin A, roridin A, and anguidine); urethane, siRNA, antisense pharmaceuticals; (2) Anti-autoimmune disease drugs: Cyclosporine, cyclosporine A, aminocaproic acid, azathioprine, bromocriptine, chlorambucil, chloroquine, cyclophosphamide, corticosteroids (including the group consisting of amcinonide, betamethasone, budesonide, hydrocortisone, flunisolide, fluticasone propionate, fluocortodanazole, dexamethasone, triamcinolone acetonide, beclomethasone dipropionate), DHAE, etanercept, hydroxychloroquine, infliximab, meloxicam, methotrexate, mycophenolate mofetil, prednisone, sirolimus, tacrolimus; (3) Anti-infective drugs: a) Aminoglycosides: Amikacin, Astromicin, Gentamicins (Netilmicin, Sisomicin, Isepamicin), Hygromycin B, Kanamycins (Amikacin, Arbekacin, Bekanamycin, Dibekacin, Tobramycin), Neomycins (Framycetin, Paromomycin, Ribostamycin), Netilmicin, Spectinomycin, Streptomycin, Tobramycin, Vedalamycin; b) Amphenicols: Azidamfenicol, Chloramphenicol, Florfenicol, Thiamphenicol; c) Ansamycins: Geldanamycin, Herbimycin; d) Carbapenems: Biapenem, Doripenem, Ertapenem, Imipenem / Cilastatin, Meropenem, Panipenem; e) Cephems: Carbacephems (Loracarbef), Cefacetrile, Cefaclor, Cefradine, Cefadroxil, Cefalonium, Cefaloridine, Cefalothin or Cephalosporin, Cefalexin, Cefaloglycin, Cefamandole, Cefapirin, Cefatrizine, Cefazafur, Cefazedone, Cefazolin, Cefbuperazone, Cefcapene, Cefdaloxime, Cefepime, Cefminox, Cefoxitin, Cefprozil, Cephalosporin, Ceftezole, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefepime, Cefetamet, Cefmenoxime, Cefodizime, Cefonicid, Cefoperazone, Ceforanide, Cefotaxime, Cefothiam, Cefozopran, Cefalexin, Cefpimizole, Cefpiramide, Cefpiram, Cefpodoxime, Cefprozil, Cefquinome, Cefsulodin, Cefotaxime, Cefazone, Cefamycin (Cefoxitin, Cefotetan, Cefmetazole), Oxacephems (Flomoxef, Latamoxef); f) Glycopeptides: Bleomycin, Vancomycin (Oritavancin, Telavancin), Teicoplanin (Dalbavancin), Lantibiotics; g) Glycylcyclines: Tigecycline; h) β-Lactamase inhibitors: Penams (Sulbactam, Tazobactam), Clavams (Clavulanic acid); i) Lincosamides: Clindamycin, Lincomycin; j) Lipopeptides: Daptomycin, A54145, Calcium-dependent antibiotic (CDA); k) Macrolides: Azithromycin, Cethromycin, Clarithromycin, Dirithromycin, Erythromycin, Flurithromycin, Josamycin, Ketolides (Telithromycin, Cethromycin), Midecamycin, Myocamycin, Oleandomycin, Rifamycins (Rifampicin, Rifampin, Rifabutin, Rifapentine), Roxithromycin, Roxithromycin, Spectinomycin, Spiramycin, Tacrolimus (FK506), Troleandomycin, Telithromycin; l) Monobactams: Aztreonam, Tigemonam; m) Oxazolidinones: Linezolid; n) Penicillins: Amoxicillin, Ampicillin, Pivampicillin, Hetacillin, Bacampicillin, Methicillin, Talampicillin, Azidocillin, Azlocillin, Benzylpenicillin, Benzathine benzylpenicillin, Benzathine phenoxymethylpenicillin, Cromocillin, Procaine benzylpenicillin, Carbenicillin (Carindacillin), Cloxacillin, Dicloxacillin, Epicillin, Flucloxacillin, Mesylinam (Pivmecillinam), Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penamecillin, Penicillin, Phenethicillin, Phenoxymethylpenicillin, Piperacillin, Propicillin, Sulbenicillin, Temocillin, Ticarcillin; o) Polypeptides: Bacitracin, Colistin, Polymyxin B; p) Quinolones: Alatrofloxacin, Balofloxacin, Ciprofloxacin, Clinafloxacin, Danofloxacin, Difloxacin, Enoxacin, Enrofloxacin, Fleroxacin, Garenoxacin, Gatifloxacin, Gemifloxacin, Grepafloxacin, Canofloxacin, Levofloxacin, Lomefloxacin, Marbofloxacin, Moxifloxacin, Nadifloxacin, Norfloxacin, Orbifloxacin, Ofloxacin, Perfloxacin, Trovafloxacin, Grepafloxacin, Sitafloxacin, Sparfloxacin, Temaflloxacin, Tosufloxacin, Trovafloxacin; q) Streptogramins: Pristinamycin, Quinupristin / Dalfopristin; r) Sulfonamides: mafenide, prontosil, sulfacetamide, sulfamethizole, sulfanilamide, sulfasalazine, sulfisoxazole, trimethoprim, trimethoprim - sulfamethoxazole (cotrimoxazole); s) Steroid antibacterial agents: selected from fusidic acid; t) Tetracyclines: doxycycline, chlortetracycline, chromocycline, demeclocycline, lymecycline, meclocycline, methacycline, minocycline, oxytetracycline, penimepicycline, rolitetracycline, tetracycline, glycylcyclines (including tigecycline); u) Other types of antibiotics: annonacin, arsphenamine, bacteriophage inhibitor (bacitracin), DADAL / AR inhibitor (cycloserine), dactiostatin, discodermolide, eleutherobin, epothilone, ethambutol, etoposide, faropenem, fusidic acid, furazolidone, isoniazid, laurimolide, metronidazole, mupirocin, mycolactone, NAM synthesis inhibitor (fosfomycin), nitrofurantoin, paclitaxel, platensimycin, pyrazinamide, quinupristin / dalfopristin, rifampin (rifampicin), tazobactam tinidazole, uvaricin; (4) Antiviral drugs: a) Entry / fusion inhibitors: apravirine, maraviroc, vicriviroc, gp41 (enfuvirtide), PRO140, CD4 (ibalizumab); b) Integrase inhibitors: raltegravir, elvitegravir, globoidnan A; c) Maturation inhibitors: bevirimat, vicafor; d) Neuraminidase inhibitors: oseltamivir, zanamivir, peramivir; e) Nucleosides and nucleotides: abacavir, acyclovir, adefovir, amdoxovir, apricitabine, brequinar, cidofovir, clevudine, decitabine, didanosine (DDI), emtricitabine, entecavir, famciclovir, fluorouracil (5-FU), 3'-fluoro-substituted 2',3'-dideoxynucleoside analogs (including the group consisting of 3'-fluoro-2',3'-dideoxythymidine (FLT) and 3'-fluoro-2',3'-dideoxyguanosine (FLG)), homoharringtonine, ganciclovir, idoxuridine, lamivudine (3TC), L-nucleosides (including the group consisting of β-L-thymidine and β-L-2'-deoxycytidine), penciclovir, rasburicase, ribavirin, stavudine, stavudine set (d4T), talibuvirine (viramidine), telbivudine, tenofovir, trifluridine, valacyclovir, valganciclovir, zalcitabine (ddC), zidovudine (AZT); f) Non-nucleosides: amantadine, atetoviridine, capravirine, diarylpyrimidine (etravirine, rilpivirine), delavirdine, docosanol, emivirine, efavirenz, foscarnet (phosphonoformic acid), imiquimod, interferon α, lobucavir, lodenosine, metisazone, nevirapine, NOV-205, peginterferon α, podophyllotoxin, rifampicin, rimantadine, resiquimod (R-848), tromantadine; g) Protease inhibitors: amprenavir, atazanavir, boceprevir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, preclinavir, ritonavir, saquinavir, telaprevir (VX-950), tipranavir; h) Other antiviral drugs: abzyme, arbidol, calanolide A, celastrol, cyanovirin-N, diarylpyrimidine, epigallocatechin gallate (EGCG), foscarnet, griffithsin, talibuvirine (viramidine), hydroxyurea, KP-1461, miltefosine, preclinavir, portmanteau inhibitor, ribavirin, sericlib; (5) ３ H, １１ C, １４ C, １８ F, ３２ P, ３５ S, ６４ Cu, ６８ Ga, ８６ Y, ９９ Tc, １１１ In, １２３ I, １２４ I, １２５ I, １３１ I, １３３ Xe, １７７ Lu, ２１１ At, or ２１３ a radioisotope (radionuclide) that can be selected from Bi; (6) A chromophore molecule having the ability to absorb UV light, fluorescent light, IR light, near-IR light, and visible light; a class or subclass of xanthophores, erythrophores, iridophores, leucophores, melanophores, cyanophores, and phosphors, wherein the phosphor is a fluorescent chemical substance that re-emits light with light, a visually light-sensitive molecule, a luminescent molecule, a luminescence molecule, a class or subclass of luciferin compounds, a visible light-transmitting molecule, a luminescent molecule, a luminescence molecule, a luciferin compound; for example, the following non-protein organic phosphors: xanthene derivatives (including fluorescein, rhodamine, Oregon Green, eosin, and Texas Red); cyanine derivatives (including cyanine, indocarbocyanine, oxacarbocyanine, thiacarbocyanine, and merocyanine); squalene derivatives and ring-substituted squaraines (including Seta, SeTau, and Squarene dyes); naphthalene derivatives (including dansyl and prodan derivatives); coumarin derivatives; oxadiazole derivatives (including pyridyloxazole, nitrobenzoxadiazole, and benzoxadiazole); anthracene derivatives (including anthraquinones including DRAQ5, DRAQ7, and CyTRAK Orange); pyrene derivatives (cascade blue); oxazine derivatives (including Nile Red, Nile Blue, cresyl violet, and oxazine 170). Acridine derivatives (including proflavine, acridine orange, and acridine yellow). Arylmethine derivatives (including auramine, crystal violet, and malachite green). Tetrapyrrole derivatives (including porphyrin, phthalocyanine, bilirubin); any analogs and derivatives of the following phosphor compounds: CF dyes, DRAQ and CyTRAK probes, BODIPY, Alexa Fluor, DyLight Fluor, Attto and Trancy, FluorProbes, Abberior dyes, DY and MegaStokes dyes, SulfoCy dyes, HiLyte Fluor, Seta, SeTa and Square dyes, Quasar and Cal Fluor dyes, SureLight dyes (APC, RPE-PerCP, phycobilisomes), APC, APCXL, RPE, BPE, allophycocyanin (APC), aminocoumarin, APC-Cy7 conjugate, BODIPY-FL, cascade blue, Cy2, Cy3, Cy3.5, Cy3B, Cy5, Cy5.5, Cy7, fluorescein, FluorX, hydroxycoumarin, rhodamine B, lucifer yellow, methoxycoumarin, NBD, Pacific Blue, Pacific Orange, PE-Cy5 conjugate, PE-Cy7 conjugate, PerCP, R-phycoerythrin (PE), Red613, Seta-555-azide, Seta-555-DBCO, Seta-555-NHS, Seta-580-NHS, Seta-680-NHS, Seta-780-NHS, Seta-APC-780, Seta-PerCP-680, Seta-R-PE-670, SeTau380-NHS, SeTau405-maleimide, SeTau405-NHS, SeTau425-NHS, SeTau647-NHS, Texas Red, TRITC, TruRed, X-rhodamine, 7-AAD (7-aminoactinomycin D, CG selectivity), acridine orange, chromomycin A3, CyTRAK orange (red excitation dark), DAPI, DRAQ5, DRAQ7, ethidium bromide, Hoechst 33258, Hoechst 33342, LDS751, mitramycin, propidium iodide (PI), SYTOX blue, SYTOX green, SYTOX orange, thiazole orange, TO-PRO: cyanine monomer, TOTO-1, TO-PRO-1, TOTO-3, TO-PRO-3, YOseta-1, YOYO-1;Fluorescent dyes containing the following compounds or their derivatives: DCFH (2',7'-dichlorodihydro-fluorescein, oxidized form), DHR (dihydrorhodamine 123, oxidized form, photocatalytic oxidation), Fluo-3 (AM ester, pH > 6), Fluo-4 (AM ester, pH 7.2), Indo-1 (AM ester, low / high calcium (Ca; ２＋ )), SNARF (pH 6 / 9), allophycocyanin (APC), AmCyan1 (tetramer, Clontech), AsRed2 (tetramer, Clontech), Azami Green (monomer), azurite, B-phycoerythrin (BPE), celestine, CyPet, DsRed monomer (Clontech), DsRed2 ("RFP"), EBFP, EBFP2, ECFP, EGFP (weak dimer), emerald (weak dimer), EYFP (weak dimer), GFP (S65A mutant), GFP (S65C mutant), GFP (S65L mutant), GFP (S65T mutant), GFP (Y66F mutant), GFP (Y66H mutant), GFP (Y66W mutant), GFP ｕｖ , HcRed1, J-Red, catusya, Kusabira Orange (monomer, MBL), mCFP, mCherry, mCitrine, Midoriishi Cyan (dimer, MBL), mKate (TagFP635, monomer), mKeima-Red (monomer), mKO, mOrange, mPlum, mRaspberry, mRFP1 (monomer), mStrawberry, mTFP1, mTurquoise2, P3 (phycobilisome complex), peridinin chlorophyll (PerCP), R-phycoerythrin (RPE), T-Sapphire, TagCFP (dimer), TagGFP (dimer), TagRFP (dimer), TagYFP (dimer), tdTomato (tandem dimer), tops, TurboFP602 (dimer), TurboFP635 (dimer), TurboGFP (dimer), TurboRFP (dimer), TurboYFP635 (dimer), Venus, wild-type GFP, YPet, ZsGreen1 (tetramer), ZsYellow1 (tetramer). (7) A cell-binding ligand or receptor agonist that can be selected from the following: folic acid derivatives; glutamic acid urea derivatives; somatostatin and its analogs (selected from the group consisting of octreotide (Sandostatin) and lanreotide (Somatuline)); aromatic sulfonamides; pituitary adenylate cyclase-activating peptide (PACAP) (PAC1); vasoactive intestinal peptide (VIP / PACAP) (VPAC1, VPAC2); melanocyte-stimulating hormone (α-MSH); cholecystokinin (CCK) / gastrin receptor agonist; bombesin (Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2 (selected from the group consisting of); gastrin-releasing peptide (GRP); neurotensin receptor ligand (NTR1, NTR2, NTR3); substance P (NK1 receptor) ligand; neuropeptide Y (Y1 - Y6); RGD (Arg-Gly-Asp), NGR (Asn-Gly-Arg), dimeric and multimeric cyclic RGD peptides (selected from cRGDfV), TAASGVRSMH and LTLRWLVGLMS (chondroitin sulfate proteoglycan NG2 receptor ligand) and homing peptides including F3 peptide; cell-penetrating peptides (CPPs); luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, and gonadotropin-releasing hormone (GnRH) agonists that act by targeting follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the same way as testosterone production, and are selected from the group consisting of buserelin (Pyr-His-Trp-Ser-Tyr-D-Ser(OtBu)-Leu-Arg-Pro-NHEt), gonadorelin (Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 ), goserelin (Pyr-His-Trp-Ser-Tyr-D-Ser(OtBu)-Leu-Arg-Pro-AzGly-NH2), histrelin (Pyr-His-Trp-Ser-Tyr-D-His(N-benzyl)-Leu-Arg-Pro-NHEt), leuprorelin (Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt), nafarelin (Pyr-His-Trp-Ser-Tyr-2Nal-Leu-Arg-Pro-Gly-NH 2 ), tryptorelin (Pyr-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH 2 ), nafarelin, deslorelin, abarelix (Ac-D-2Nal-D-4-chloroPhe-D-3-(3-pyridyl)Ala-Ser-(N-Me)Tyr-D-Asn-Leu-isopropyl-Pro-DAla-NH 2 ), cetrorelix (Ac-D-2Nal-D-4-chloroPhe-D-3-(3-pyridyl)Ala-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH 2 ), degarelix (Ac-D-2Nal-D-4-chloroPhe-D-3-(3-pyridyl)Ala-Ser-4-amioPhe(L-hydroorotyl)-D-4-amioPhe(carbamoyl)-Leu-isopropyl Lys-Pro-D-Ala-NH 2 ), and ganirelix (Ac-D-2Nal-D-4-chloroPhe-D-3-(3-pyridyl)Ala-Ser-Tyr-D-(N9, N10-diethyl)-homoArg-Leu-(N9, N10-diethyl)-homoArg-Pro-D-Ala-NH 2 ); a peptide hormone selected from the group consisting of; a pattern recognition receptor (PRR) selected from the group consisting of Toll-like receptor (TLR) ligands, C-type lectins, and Nod-like receptor (NLRs) ligands; a calcitonin receptor agonist; an integrin receptor and its receptor subtypes (α Ｖ β １ α Ｖ β ３ α Ｖ β ５ , α Ｖ β ６ , α ６ β ４ , α ７ β １ , α Ｌ β ２ , α ＩＩｂ β ３ is selected from the group consisting of.) Agonists (GRGDSPK, cyclo(RGDFV)(L1) and its derivatives [cyclo(-N(Me)R-GDFV), cyclo(R-Sar-DFV), cyclo(RG-N(Me)D-fV), cyclo(RGD-N(Me)f-V), cyclo(RGDF-N(Me)V-)(cilengitide)]; nanobodies (derivatives of VHH(camel Ig)); domain antibodies (dAb, derivatives of VH or VL domains), bispecific T cell engagers (BiTE, bispecific antibodies); bispecific affinity retargeting (DART, bispecific antibodies); tetravalent tandem antibodies (TandAb, dimerized bispecific antibodies); anticalins (derivatives of lipocalins); adnectins (tenth FN3(fibronectin)); designed ankyrin repeat proteins (DARPins); avimers; EGF receptor and VEGF receptor agonists. (8) A pharmaceutically acceptable salt, acid, derivative, hydrate or hydrated salt of any of the above drugs; or a crystal structure; or an optical isomer, racemate, diastereomer, or enantiomer.

9. The method according to any one of claims 1 to 3, wherein the cytotoxic or functional molecule is a polyalkylene glycol (including poly(ethylene glycol) (PEGs), poly(propylene glycol), copolymers of ethylene oxide or propylene oxide, or analogs thereof).

10. The method according to any one of claims 1 to 3, wherein the cytotoxic or functional molecule is a cell-binding ligand, a cell receptor agonist, or a cell receptor-binding molecule, and the conjugate is used as a target conductor / director for delivery to malignant cells or for modulating or costimulating a desired immune response or altering a signaling pathway. Claim 11 The cytotoxic or functional molecule is selected from tubulysins, calicheamicins, auristatins, maytansinoids, CC-1065 analogs, daunorubicin and doxorubicin compounds, taxanoids (taxanes), cryptophycins, epothilones, benzodiazepine dimers (pyrrolobenzodiazepine dimers (PBD), tomamycin dimers, anthramycin dimers, indolinobenzodiazepine dimers, imidazobenzothiadiazepine dimers, or oxazolidinobenzodiazepine dimers, and derivatives thereof), calicheamicins and enediyne antibiotics, actinomycins, amanitins, azaserines, bleomycins, epirubicins, tamoxifen, idarubicin, dolastatin / auristatin (monomethyl auristatin E, MMAE, MMAF, auristatin PYE, auristatin TP, auristatin 2-AQ, 6-AQ, EB (AEB), and EFP (AEFP), and derivatives thereof), duocarmycins, geldanamycins, methotrexate, thiotepa, vinca alkaloids (vindesines), vincristines, hemiasterlins, nazumamides, microginins, radiosumins, alterobactins, microsclerodermins, theonellamides, esperamicins, siRNA, miRNA, piRNA, nucleolytic enzymes, and / or pharmaceutically acceptable salts, acids, and / or analogs, derivatives, hydrates or hydrated salts of any of the above molecules; or crystal structures; or optical isomers, racemates, diastereomers or enantiomers, the method according to any one of claims 1 to 3.

12. The cell-binding agent / molecule is selected from antibodies, the method according to any one of claims 1 to 3.

13. The method according to any one of claims 1 to 3, wherein the cell binding agent / molecule is selected from the group consisting of an antibody, an antibody-like protein, a full-length antibody (polyclonal antibody, monoclonal antibody, dimer, multimer), or a multispecific antibody (selected from bispecific antibody, trispecific antibody, or tetravalent antibody); a single-chain antibody, an antibody fragment that binds to a target cell, a monoclonal antibody, a single-chain monoclonal antibody, a monoclonal antibody fragment that binds to a target cell, a chimeric antibody, a chimeric antibody fragment that binds to a target cell, a domain antibody, a domain antibody fragment that binds to a target cell, a surface remodeling antibody, a single-chain surface remodeling antibody, a surface remodeling antibody fragment that binds to a target cell, a humanized antibody or a surface remodeling humanized antibody, a single-chain humanized antibody or a humanized antibody fragment that binds to a target cell, and an anti-idiotype (anti-Id) antibody.

14. The method according to any one of claims 1 to 3, wherein the cell binding agent / molecule can target tumor cells, virus-infected cells, microbe-infected cells, parasite-infected cells, autoimmune disease cells, activated tumor cells, bone marrow cells, activated T cells, or melanocytes, or cells expressing one or more of the following antigens or receptors: CD2, CD2R, CD3, CD3γδ, CD3ε, CD4, CD5, CD6, CD7, CD8, CD8α, CD8β, CD9, CD10, CD11a, CD11b, CD11c, CD12, CD12w, CD13, CD14, CD15, CD15s, CD15u, CD16, CD16a, CD16b, CD17, CDw17, CD18, CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD26, CD27, CD28, CD29, CD30, CD31, CD32, CD33, CD34, CD35, CD36, CD37, CD38, CD39, CD40, CD41, CD42, CD42a, CD42b, CD42c, CD42d, CD43, CD44, CD44R, CD45, CD45RA, CD45RB, CD45RO, CD46, CD47, CD47R, CD48, CD49a, CD49b, CD49c, CD49e, CD49f, CD50, CD51, CD52, CD53, CD54, CD55, CD56, CD57, CD58, CD59, CD60, CD60a, CD60b, CD60c, CD61, CD62E, CD62L, CD62P, CD63, CD64, CD65, CD65s, CD66, CD66a, CD66b, CD66c, CD66d, CD66e, CD66f, CD67, CD68, CD69, CD70, CD71, CD72, CD73, CD74, CD74, CD75, CD75s, CD76, CD77, CD78, CD79, CD79a, CD79b, CD80, CD81, CD82, CD83, CD84, CDw84, CD85, CD86, CD87, CD88, CD89, CD90, CD91, CD92, CDw92, CD93, CD94, CD95, CD96, CD97, CD98, CD99, CD99R, CD100, CD101, CD102, CD103, CD104, CD105, CD106, CD107, CD107a, CD107b, CD108, CD109, CD110, CD111, CD112, CD113, CDw113,CD114, CD115, CD116, CD117, CD118, CD119, CDw119, CD120a, CD120b, CD121a, CD121b, CDw121b, CD122, CD123, CDw123, CD124, CD125, CDw125, CD126, CD127, CD128, CDw128, CD129, CD130, CD131, CDw131, CD132, CD133, CD134, CD135, CD136, CDw136, CD137, CDw137, CD138, CD139, CD140a, CD140b, CD141, CD142, CD143, CD144, CD145, CDw145, CD146, CD147, CD148, CD149, CD150, CD151, CD152, CD153, CD154, CD155, CD156a, CD156b, CDw156c, CD157, CD158a, CD158b, CD159a, CD159b, CD159c, CD160, CD161, CD162, CD162R, CD163, CD164, CD165, CD166, CD167, CD167a, CD168, CD169, CD170, CD171, CD172a, CD172b, CD172g, CD173, CD174, CD175, CD175s, CD176, CD177, CD178, CD179, CD180, CD181, CD182, CD183, CD184, CD185, CD186, CDw186, CD187, CD188, CD189, CD190, CD191, CD192, CD193, CD194, CD195, CD196, CD197, CD198, CDw198, CD199, CDw199, CD200, CD200a, CD200b, CD201, CD202, CD202b, CD203, CD203c, CD204, CD205, CD206, CD207, CD208, CD209, CD210, CDw210, CD212, CD213a1, CD213a2, CDw217, CDw218a, CDw218b, CD220, CD221, CD222, CD223, CD224, CD225, CD226, CD227, CD228, CD229, CD230, CD231, CD232, CD233, CD234, CD235a, CD235ab, CD235b, CD236, CD236R, CD238, CD239, CD240, CD240CECD240D, CD241, CD242, CD243, CD244, CD245, CD246, CD247, CD248, CD249, CD252, CD253, CD254, CD256, CD257, CD258, CD261, CD262, CD263, CD265, CD266, CD267, CD268, CD269, CD271, CD273, CD274, CD275, CD276 (B7-H3), CD277, CD278, CD279, CD280, CD281, CD282, CD283, CD284, CD289, CD292, CDw293, CD294, CD295, CD296, CD297, CD298, CD299, CD300a, CD300c, CD300e, CD301, CD302, CD303, CD304, CD305, CD306, CD309, CD312, CD314, CD315, CD316, CD317, CD318, CD319, CD320, CD321, CD322, CD324, CDw325, CD326, CDw327, CDw328, CDw329, CD331, CD332, CD333, CD334, CD335, CD336, CD337, CDw338, CD339, 4-1BB, 5AC, 5T4 (trophoblast glycoprotein, TPBG, 5T4, Wnt activation inhibitory factor 1 or WAIF1), adenocarcinoma antigen, AGS-5, AGS-22M6, activin receptor-like kinase 1, AFP, AKAP-4, ALK, alpha integrin, alphavbeta6, aminopeptidase N, amyloid beta, androgen receptor, angiopoietin 2, angiopoietin 3, annexin A1, anthrax toxin protective antigen, anti-transferrin receptor, AOC3 (VAP-1), B7-H3, anthrax, BAFF (B-cell activating factor), BCMA, B-lymphocytes, bcr-ab1, bombesin, BORIS, C5, C242 antigen, CA125 (carbohydrate antigen 125, MUC16), CA-IX (or CAIX, carbonic anhydrase 9), CALLA, CanAg, canine IL31, carbonic anhydrase IX, cardiac myosin, CCL11 (C-C motif chemokine 11), CCR4 (CC chemokine receptor type 4, CD194), CCR5, CD3E (epsilon), CEA (carcinoembryonic antigen), CEACAM3, CEACAM5 (carcinoembryonic antigen), CFD (factor D), Ch4D5, cholecystokinin 2 (CCK2R)CLDN18 (Claudin-18), Clamping factor A, cMet, CRIPTO, FCSF1R (Colony Stimulating Factor 1 Receptor, CD115), CSF2 (Colony Stimulating Factor 2, Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)), CSP4, CTLA4 (Cytotoxic T Lymphocyte Associated Protein 4), CTAA16.88 Tumor Antigen, CXCR4 (CD184), CXC Chemokine Receptor Type 4, cADP Ribose Hydrolase, Cyclin B1, CYP1B1, Cytomegalovirus, Cytomegalovirus Glycoprotein B, Dabigatran, DLL3 (Delta-like Ligand 3), DLL4 (Delta-like Ligand 4), DPP4 (Dipeptidyl Peptidase 4), DR5 (Death Receptor 5), Escherichia coli Shiga Toxin Type 1, Escherichia coli Shiga Toxin Type 2, ED-B, EGFL7 (EGF-like Domain Containing Protein 7), EGFR, EGFRII, EGFRvIII, Endoglin, Endothelin B Receptor, Endotoxin, EpCAM (Epithelial Cell Adhesion Molecule), EphA2, Epithin, ERBB2 (Epidermal Growth Factor Receptor 2), ERBB3, ERG (TMPRSS2ETS Fusion Gene), Escherichia coli, ETV6-AML, FAP (Fibroblast Activation Protein α), FCGR1, α-Fetoprotein, Fibrin II, β Chain, Fibronectin External Domain B, FOLR (Folate Receptor), Folate Receptor α, Folate Hydrolase, RSV Fos-related Antigen 1 F Protein, Frizzled Receptor, Fucosyl GM1, GD2 Ganglioside, G-28 (Cell Surface Glycolipid Antigen), GD3 Idiotype, GloboH, Glypican 3, N-Glycolylneuraminic Acid, GM3, GMCSF Receptor α Chain, Growth Differentiation Factor 8, GP100, GPNMB (Transmembrane Protein NMB), GUCY2C (Guanylate Cyclase 2C, Guanylate Cyclase C (GC-C), Intestinal Guanylate Cyclase, Guanylate Cyclase-C Receptor, Heat Stable Enterotoxin Receptor (hSTAR)), Heat Shock Protein, Hemagglutinin, Hepatitis B Surface Antigen, Hepatitis B Virus, HER1 (Human Epidermal Growth Factor Receptor 1), HER2, HER2 / neu, HER3 (ERBB-3), IgG4, HGF / SF (Stem Cell Growth Factor / Scatter Factor), HHGFGR, HIV-1, Histone Complex, HLA-DR (Human Leukocyte Antigen), HLA-DR10, HLA-DRB,HMWMAA, human chorionic gonadotropin, HNGF, human cell scattering factor receptor kinase, HPV E6 / E7, Hsp90, hTERT, ICAM-1 (intercellular adhesion molecule 1), idiotype, IGF1R (IGF-1, insulin-like growth factor 1 receptor), IGHE, IFN-γ, influenza hemagglutinin, IgE, IgE Fc region, IGHE, interleukins (including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-6R, IL-7, IL-8, IL-9, IL-10, IL-11, L-12, IL-13, IL-15, IL-17, IL-17A, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-27, or IL-28.), IL-31RA, ILGF2 (insulin-like growth factor 2), integrin (α4, α, ＩＩＩｂ β ３ αvβ3, α ４ β ７ , α5β1, α6β4, α7β7, αIIβ3, α5β5, ανβ5), interferon γ-induced protein, ITAGA2, ITGB2, KIR2D, Kappa Ig, LCK, Le, legumain, Lewis-Y antigen, LFA-1 (lymphocyte function-associated antigen 1, CD11a), LHRH, LINGO-1, lipoteichoic acid, LIV1A, LMP2, LTA, MAD-CT-1, MAD-CT-2, MAGE-1, MAGE-2, MAGE-3, MAGEA1, MAGEA3, MAGE4, MART1, MCP-1, MIF (macrophage migration inhibitory factor or glycosylation inhibitory factor (GIF)), MS4A1 (membrane-spanning 4-domain subfamily A member 1), MSLN (mesothelin), MUC1 (mucin 1, cell surface-associated (MUC1) or Polymorphic epithelial mucin (PEM)), MUC1-KLH, MUC16 (CA125), MCP1 (monocyte chemoattractant protein 1), MelanA / MART1, ML-IAP, MPG, MS4A1 (membrane-spanning type 4-domain subfamily A), MYCN, myelin-associated glycoprotein, myostatin, NA17, NARP-1, NCA-90 (granulocyte antigen), Nectin-4 (ASG-22ME), NGF, nerve apoptosis regulatory protease 1, NOGO-A, Notch receptor, nucleolin, Neu oncogene product, NY-BR-1, NY-ESO-1, OX-40, OxLDL (oxidized low-density lipoprotein), OY-TES1, P21, p53 non-mutant, P97, Page4, PAP, paratope against (N-glycolylneuraminic acid), PAX3, PAX5, PCSK9, PDCD1 (PD-1, programmed cell death tan Protein 1), PDGF-Rα, (platelet-derived growth factor receptor α), PDGFR-β, PDL-1, PLAC1, PLAP-like testicular alkaline phosphatase, platelet-derived growth factor receptor β, sodium phosphate cotransporter, PMEL17, polysialic acid, proteinase 3 (PR1), prostate cancer, PS (phosphatidylserine), prostate cancer cells, Pseudomonas aeruginosa, PSMA, PSA, PSCA, rabies virus glycoprotein, RHD (Rh polypeptide 1 (RhPI)), rhesus factor, RANKL, PhoC, Ras variant, RG55, ROBO4, RS virus, RON, ROR1, sarcoma metastasis breakpoint, SART3, sclerostin, SLAMF7 (SLAM family member 7), selectin P, SDC1 (syndecan 1), sLe(a), somatomedin C, SIP (sphingosine-1-phosphate), somatostatin, sperm protein 17, SSX2, STEAP1 (six-transmembrane epithelial antigen of prostate 1), STEAP2, STn, TAG-22 (tumor-associated glycoprotein 72), survivin, T cell receptor, T cell transmembrane protein, TEM1 (tumor epithelial marker 1), TENB2, tenascin C (TN-C), TGF-α, TGF-β (transforming growth factor β), TGF-β1, TGF-β2 (transforming growth factor β2), Tie (CD202b), Tie2, TIM-1 (CDX-014), TN, TNF, TNF-α, TNFRSF8, TNFRSF10B (tumor necrosis factor receptor superfamily member 10B), TNFRSF13B (tumor necrosis factor receptor superfamily member 13B), TPBG (trophoblast glycoprotein), TRAIL-R1 (tumor necrosis apoptosis-inducing ligand receptor 1), TRAILR2 (death receptor 5 (DR5)), tumor-associated calcium signal transducer 2, tumor-specific glycosylation of MUC1, TWEAK receptor, TYRP1 (glycoprotein 75), TRP-2, tyrosinase, VCAM-1, VEGF, VEGF-A, VEGF-2, VEGFR-1, VEGFR2, or vimentin, WT1, XAGE1, or any insulin growth factor receptor-expressing cells, or any epithelial growth factor receptor.

15. The method according to claim 14, wherein the tumor cells are selected from lymphoma cells, myeloma cells, renal cells, breast cancer cells, prostate cancer cells, ovarian cancer cells, colorectal cancer cells, gastric cancer cells, squamous cell carcinoma cells, small cell lung cancer cells, non-small cell lung cancer cells, or testicular cancer cells.

16. The method according to any one of claims 1 to 3, wherein the cell-binding molecule / agent is selected from IgG antibodies, monoclonal antibodies, or IgG antibody-like proteins, and the conjugate compound of formula (I) has the following structure, the structure of ST1, ST2, ST3, ST4, ST5, or ST6: 【Chemical 56】 【Chem.】 In the formula, Z １ 、Z ２ 、X, Y, L １ 、L ２ 、 【Chemical 57】 , m １ , and the cytotoxic and / or functional molecule have the same definition as in claim 1.

17. The method according to claim 1, wherein the compound of formula (II) has any of the following structures: 【Chemical Formula 58】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 [Chemical] 【Chem.】 【Chem.】 [Chemical] 【Chem.】 【Chem.】

18. The method according to any one of claims 1 to 3, wherein the conjugate compound of formula (I) has the formula of 103, 113, 117, 120, 127, 129, 131, 133, 135, 140, 142, 150, 152, 169, 177, 186, 190, 197, 217a, 217b, 217c, 217d, 217e, 217f, 223a, 223b, 223c, 223d, 223e, 223f, 245a, 245b, 245c, 245d, 245e, 245f, 255, 303a, 303b, 303c, 303d, 303e, 303f, 312a, 312b, 312c, 316a, 316b, 316c, 316d, 316e, 316f, 320a, 320b, 320c, 325a, 325b, 325c, 340a, 340b, 340c, 342a, 342b, 342c, 356, 384, 386, 393, 395a, 395b, 397, 399a, 399b, 399c, 401, 404, 407, 411, 413, 416, 419, 421, 424, A-3a, A-4a, A-5a, B-3a, B-6a, B-9a, B-12a, B-15a, B-18a, B-19a, B-20a, B-21a, B-22a, B-23a, B-24a, B-25a, B-26a, B-28a, D-1a, or D-2a shown below: 【Chemical Formula 59】 【Chem.】 [Chemical] 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 【Chem.】 In the formula, when m is not shown in the formula, it is 0 to 20; mAb is an antibody; m1 and n have the same definitions as in claim 1.

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