Branched ligature and conjugate of amanita toxin

JP2026097851APending Publication Date: 2026-06-16HANGZHOU DAC BIOTECH CO LTD
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
HANGZHOU DAC BIOTECH CO LTD
Filing Date
2026-02-13
Publication Date
2026-06-16

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Abstract

This invention provides a side-chain coupled compound of a cell-binding molecule having a branched linker and an amanita toxin compound. [Solution] A side-chain conjugated compound of formula (I), TIFF2026097851000286.tif25170 In one embodiment, a side-chain conjugated compound is provided, in which T is a cell-binding agent / molecule, W is a C1-C18 extension unit, and D is an amanita toxin, or an isotope of a chemical element, or a pharmaceutically acceptable salt, hydrate, or hydrated salt; or a polymorphic crystal; or an optical isomer, racemate, diastereomer, or enantiomer thereof.
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Claims

1. Side-chain conjugated compounds of formula (I): 【Chemistry 1】 During the ceremony, 【Chemistry 2】 represents a single bond; n is between 1 and 30; T stands for antibody; single-chain antibody; antibody fragment that binds to target cells; monoclonal antibody. Single-chain monoclonal antibody; monoclonal antibody fragment that binds to target cells; Mela antibody; chimeric antibody fragment that binds to target cells; domain antibody; binds to target cells. Domain antibody fragments; antibody-mimicking adnectin; DARPins; lymphocytes Cain; hormones; vitamins; growth factors; colony-stimulating factors; nutrient transport molecules (transfers) (Ferrin); and / or albumin, polymers, dendrimers, liposomes, nanoparticles, small Small molecules, cell-binding peptides, or proteins attached to cells or (viral) capsids It is a cell-binding agent / molecule selected from the group consisting of chlorine; L １ and L ２ These are independently, identical or different, O, NH, N, S, P, NNH, NHN H、N(R ３ )、N(R １２ )、N(R １２ )N(R １２’ )、CH、CO、C(O)N H, C(O)O, NH C(O)NH, NH C(O)O, or the formula (OCH ２ CH ２ ) ｐ OR １２ (OCH ２ CH(CH ３ )) ｐ OR １２ ,NH(CH) ２ CH ２ O) ｐ R １２ ,NH (CH ２ CH(CH ３ )O) ｐ R １２ 、N[(CH ２ CH ２ O) ｐ R １２ ]-[(CH ２ CH ２ O) ｐ’ R １２’ ], (OCH ２ CH ２ ) ｐ COOR １２ , or CH ２ CH ２ (OCH ２ CH ２ ) ｐ COOR １２ Polyethylene oxy units (wherein p and p' are independent) And an integer selected from 0 to approximately 1000), or a combination thereof; C １ -C ８ Alkyl; C ２ -C ８ Heteroalkyl, alkylcycloalkyl, heterocycloalkyl ; C ３ -C ８ Aryl, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, hetero Alkylcycloalkyl, alkylcarbonyl, or heteroaryl; or (Aa)r( r = 1 to 12 (1 to 12 amino acid units), composed of natural or non-natural amino acids, the same or These are dipeptides, tripeptides, tetrapeptides, pentapeptides, and hexapeptides with different sequences. Butyrates, heptapeptides, octapeptides, nonapeptides, decapeptides, undecapeptides (A cydo or dodecapeptide unit, independently selected from;) W is C １ ~C １８ It is an expansion unit, usually a self-destructing spacer, peptide unit , hydrazone, disulfide, thioether, ester, or amide bond; w is 1 or 2 or 3; V １ and V ２ These are independently O, NH, S, C １ ~C ８ Alkyl, C ２ ~C ８ Heterozygous Kill, Alkenil, or Alkinil, C ３ ~C ８ Aryl, heterocycle, carbocyclic, cycloal Kill, alkylcycloalkyl, heterocycloalkyl, heteroaralkyl, heteroal chlorocycloalkyl, or alkylcarbonyl, or (Aa)r (r = 1 to 12 (1 to 1 (2 amino acid units), and (Aa)r is a natural or non-natural amino acid, or the same or These are dipeptides, tripeptides, tetrapeptides, pentapeptides, and hexapeptides with different sequences. Butyrates, heptapeptides, octapeptides, nonapeptides, decapeptides, undecapeptides It is composed of cydo or dodecapeptide units. (CH) or (CH ２ CH ２ O) ｐ (p = A spacer unit selected from 0 to 1000; v １ and v ２ 0 is independent. 1 or 2, however, v １ and v ２ Both are 0 at the same time; v １ or v ２ If it is 0, side Chain Q １ Or Q ２ This means that one of the fragments is missing; Q １ and Q ２ These two can be expressed independently by equation (I - q1): 【Transformation 3】 During the ceremony, 【Chemistry 4】 is, L １ or L ２ This is the site where it connects; G １ and G ２ They are independent of OC(O) and NHC. (O)、C(O)、CH ２ 、NH, OC(O)NH, NHC(O)NH, O, S, B, P (O)(OH)、NHP(O)(OH)、NHP(O)(OH)NH、CH ２ P(O)( OH)NH、OP(O)(OH)O、CH ２ P(O)(OH)O、NHS(O) ２ 、NH S(O) ２ NH、CH ２ S(O) ２ NH、OS(O) ２ O、CH ２ S(O) ２ O、Ar、 ArCH ２ , ArO, ArNH, ArS, ArNR １ , or (Aa) ｑ１ is; G ３ はH、SH、! １２ 、S １２ 、C()) １２ 、\C()R １２ 、(()) R １２ 、CH ３ 、NH ２ 、NR １２ 、 ＋ NH(R １２ )、 ＋ N(R １２ )(R １２’ ) 、C(O)OH、C(O)NH ２ 、NHC(O)NH ２ 、BH ２ 、BR １２ R １２’ 、P (O)(OH) ２ 、NHP(O)(OH) ２ 、NHP(O)(NH ２ ) ２ 、S(O) ２ ( OH)、(CH ２ ) ｑ１ C(O)OH、(CH ２ ) ｑ１ P(O)(OH) ２ 、C(O)( CH ２ ) ｑ１ C(O)OH、OC(O)(CH ２ ) ｑ１ C(O)OH、NHC(O)(C H ２ ) ｑ１ C(O)OH、CO(CH ２ ) ｑ１ P(O)(OH) ２ 、NHC(O)O(C H ２ ) ｑ１ C(O)OH、OC(O)NH(CH ２ ) ｑ１ C(O)OH、NHCO(CH ２ ) ｑ１ P(O)(OH) ２ 、NHC(O)(NH)(CH ２ ) ｑ１ C(O)OH, CO NH(CH ２ ) ｑ１ P(O)(OH) ２ 、NHS(O) ２ (CH ２ ) ｑ１ C(O)OH、 CO(CH ２ ) ｑ１ S(O) ２ (OH)、NHS(O) ２ NH(CH ２ ) ｑ１ C(O)O H, OS(O) ２ NH(CH) ２ ) ｑ１ C(O)OH、NHCO(CH ２ ) ｑ１ S(O) ２ (OH)、NHP(O)(OH)(NH)(CH ２ ) ｑ１ C(O)OH、CONH(CH ２ ) ｑ１ S(O)(OH)、OP(O)(OH) ２ 、(CH ２ ) ｑ１ P(O)(NH) ２ 、NHS(O) ２ (OH)、NHS(O) ２ NH ２ 、CH ２ S(O) ２ NH ２ 、OS(O ) ２ OH、OS(O) ２ OR １ 、CH ２ S(O) ２ OR １２ 、Ar、ArR １２ 、ArO H, ArNH ２ , ArSH, ArNHR １２ , or (Aa) ｑ１ (Aa) ｑ１ X is a peptide containing identical or different sequences of natural or non-natural amino acids; １ and X ２ O, CH are independent of each other. ２ , S, S(O), NHNH, NH, N(R １２ ), ＋ NH R １２ )、 ＋ N(R １２ )(R １２’ )、C(O)、OC(O)、OC(O)O、OC (O)NH, NHC(O)NH; Y ２ O, NH, NR １２ ,CH ２ , S, NH NH, Ar; R １２ , R １２’ , R １３ , and R １３’ H and C are independent of each other. １ ~C ８ Alkyl; C ２ ~C ８ Heteroalkyl or heterocyclic; C ３ ~C ８ Aryl, Ar-A Lulkyl, cycloalkyl, alkylcycloalkyl, heterocycloalkyl, heteroal It is chlorocycloalkyl, carbocyclic, or alkylcarbonyl; Y ２ O, NH, NR １ ,CH ２ , S, NHNH, Ar; p １ , p ２ , and p ３ Each is independently between 0 and 100, but not simultaneously 0; q １ and q ２ The values ​​are independently between 0 and 24; Or, Q １ and Q ２ C is independent ２ ~C １００ Polycarboxylic acid; C ２ ~C １００ Polyalkylamine; C ６ ~C １００ Oligosaccharides or polysaccharides; C ６ ~C １００ Zwitterion betta Zwitterionic poly(()) Sulfobetaine) (PSB); (Poly(lactic acid / glycolic acid) (PLGA), Poly(A A copolymer of acrylate, chitosan, and N-(2-hydroxypropyl)methacrylamide. Poly[2-(methacryloyloxy)ethylphosphorylcholine] (PMPC), Poly -L-glutamic acid, poly(lactide-co-glycolide) (PLG), poly(lactide- Poly(ethylene glycol) (PEG), Poly(propylene glycol) (PPG), poly(lactide-co-glycol), poly(ethylene glycol) modification Peptides, amino acids, or poly(ethylene glycol), poly(ethylene glycol) containing peptides Recall) Modified lipids, poly(ethylene glycol) modified alkyl carboxylic acids, poly(ethylene glycol) Lenglycol-modified alkylamine, poly(lactide-co-glycolide, hyaluronic acid) (HA) (glycosaminoglycan), heparin / heparan sulfate (HSGAG), chondro Ithin sulfate / dermatan sulfate (CSGAG), poly(ethylene glycol)-modified alkyl Poly(ethylene glycol) sulfate, poly(ethylene glycol)-modified alkyl phosphate, or poly(ethylene glycol) (Recall) - C composed of modified alkylquaternary ammonium ６ ~C １００ Biodegradable polymer -is; Alternatively, W, Q １ Q ２ , L １ , L ２ , V １ , or V ２ One or more of the following are independent It may be absent, Q １ and Q ２ It is impossible for them to be absent at the same time; D is the amanita toxin of formula (II) below, or an isotope of a chemical element, or a pharmaceutically acceptable substance. A salt, hydrate, or hydrated salt; or a polymorphic crystalline structure; or its optical isomer. They are racemic mixtures, diastereomers, or enantiomers: 【Transformation 5】 During the ceremony, 【Transformation 6】 This is an independent linking site that connects with W; A single bond on an aromatic (indole) ring is bonded to any one of the carbon positions on the aromatic ring. It means; 【Transformation 7】 The symbol () can optionally indicate a single bond or the absence of a bond; R １ and R ２ These are independently H, OH, and CH ２ OH, CH(OH)CH ２ OH, CH(C H ３ )CH ２ OH, CH(OH)CH ３ , C １ -C ８ Alkyl, -OR １２ (ether) , C ２ -C ８ Alkenyl, Alkinyl, Heteroalkyl, -OCOR １２ (ester), -OC (=O) OR １２ (Carbonate), -OC(=O)NHR １２ (Carbamate) ; C ３ -C ８ Aryl, heterocyclic, carbocyclic, cycloalkyl, heterocycloalkyl, hetero Selected from loralkyl and alkylcarbonyl; R ３ and R ４ These are independently H, OH, -OR １２ (Ether), -OCOR １２ (S Tel), - OCOCH ３ (Acetate), -OCOR １２ (Carbonate), -OC( =O)NHR １２ (Carbamate), -OP(O)(OR １２ ) (OR12') (phosphate) ), OP(O)(NHR １２ ) (NHR １２’ (Phosphamide), O-SO ３ － , or Selected from O-glycosides; R ５ は、H、OH、NH ２ NHOH, NHNH ２ 、-OR １２ 、-NHR １２ ,NH NHR １２ , -NR １２ R １２’ , N(H)(R １２ ) R １３ CO(Aa) ｐ (amino acid Alternatively, select from the following: (where Aa is an amino acid or polypeptide, and p is 0-6.) To be done; R ６ は、H、OH、CH ２ OH、CH(OH)CH ２ OH、CH(CH ２ OH) ２ 、C H(CH) ３ )OH, CH ２ CH ２ OH, PrOH, BuOH, C １ ~C ８ Alkyl, -O R １２ (Ether), C ２ ~C ８ Alkenyl, Alkinyl, Heteroalkyl, -OCOR １２ (Ester); C ３ ~C ８ Selected from aryl, heterocyclic, or carbocyclic compounds; R ７ , R ８ , and R ９ These are independently H, OH, and CH ３ , CH (CH ３ ) ２ , CH (CH ３ )CH ２ CH ３ 、CH ２ OH、CH(OH)CH ２ OH、CH ２ CH(OH)CH ２ O H、CH(CH ２ OH) ２ 、CH ２ C(OH)(CH ２ OH) ２ 、CH ２ C(OH)(C H ３ )(CH ２ OH)、CH ２ C(OH)(CH(CH ３ ) ２ )(CH ２ OH)、CH ２ H ２ OH、PrOH、BuOH、CH ２ CO2、CO2 ２ H ２ COOH、CH(OH COOK, CH ２ CONG ２ CH ２ CH ２ CONG ２ CH ２ CH ２ CH ２ CH ２ N H ２ ,CH ２ CH ２ CH ２ NHC (=NH)NH ２ , C １ ~C ８ Alkyl, CH ２ Ar, CH ２ SH、CH ２ SR １２ 、CH ２ SSR １２ 、CH ２ SSAr、CH ２ CH ２ SCH ３ , -OR １２ (Ether), C ２ ~C ８ Alkenyl, Alkinyl, Heteroalkyl, - OCOR １２ (Ester); C ３ ~C ８ Selected from aryl, heterocyclic, or carbocyclic rings. ； R １０ and R １１ H and NH are independent. ２ OH, SH, NO ２ , halogen, -NHO H, -N ３ (Azide); -CN (Cyano); C １ ~C ８ Alkyl, C ２ ~C ８ Alkenil , alkynyl, heteroalkyl; C ３ ~C ８ Aryl, heterocyclic, or carbocyclic; -OR １２ (Ether), -OCOR １２ (Ester), -OCOCH ３ (Acetate), -OC( O) OR １２ (Carbonate), -OC(O)CH(R １２ ) NHAa (Aa is an amino acid) group), -NR １２ R １２’ (amine), -NR １２ COR １２’ (amine), -R １２ N HCOR １２’ (alkylamide), -R １２ NHR １２’ (amine), -NHR １２ N HR １２■’ NHR １２’’ (amine); -R １２ NCO-NR １２’ (urea), -R １ ２ NCOOR １２’ (Carbamate), -OCONR １２ R １２’ (Carbamate); - NR １２ (C=NH)NR １２’ R １２’’ (Guanidinium); -R １２ NHCO (A a) ｐ , -R １２ NHR １２’ CO(Aa) ｐ , -NR １２ CO(Aa) ｐ ,(amino acid (or peptide, where Aa represents an amino acid or polypeptide, and p represents 0-6); -N (R １２ ) CONR １２’ R １２’’ (Urea);-OCSNHR １２ (Thioccarbamate); -R １ ２ SH (thiol); -R １２ SR １２’ (Sulfide); -R １２ SSR １２’ (Jisoo Luffy) ;-S(O)R １２ (Sulfoxide); -S(O ２ ) R １２ (Sulfone); - SO ３ HSO ３ HSO ２ , or HSO ３ － SO ３ ２－ , or -HSO ２ － salt (Sulfites); -OSO ３ － ;-N(R １２ ) SOOR １２’ (Sulfonamide); H ２ S ２ O ５ or S ２ O ５ ２－ Salt of (metabethulfite); PO ３ SH ３ , PO ２ S ２ H ２ , P OS ３ H ２ PS ４ H ２ , or PO ３ S ３－ , PO ２ S ２ ３－ POS ３ ３－ PS ４ ３ － Salts of (mono-, di-, tri-, and tetrathiophosphates); (R １２ O) ２ POS R １２’ (Thiophage ester); HS ２ O ３ or S ２ O ３ ２－ (Thiosulfate); HS ２ O ４ or S ２ O ４ ２－ (Dithionite); (P (=S) (OR １２ )(S)(OH ) or a salt formed with a cation (phosphodithioate); -N(R １２ ) OR １２’ ( Hydroxylamine derivatives); R １２ Salts formed by C(=O)NOH or cations (H (Droxamic acid); (HOCH ２ SO ２ － or its salt (formaldehyde sulfoxylate) ); -N(R １２ ) COR １２’ (Amid); R １２ R １２’ R １２’’ NPO ３ H (T (lyalkylphosphoramide or phosphoramidic acid); or ArAr'Ar''NPO ３ H (triarylphosphonium); OP(O)(OM) １ ) (OM ２ ), OCH ２ OP ( O) (OM １ ) (OM ２ ), OSO ３ M １ O-glycoside (glucoside, galactoside) (e.g., mannoside, glucuronoside, alloside, fructoside), NH-glycoside, S- Glycoside, or CH ２ - Glycoside; M １ and M ２ These are independently H, Na, K, Ca, Mg, NH ４ , NR １’ R ２’ R ３’ And here, R １’ , R ２’ , and R ３’ is German Standing, H, C １ ~C ８ It is alkyl; Ar, Ar', and Ar'' are C ３ -C ８ a It is a reel or heteroaromatic group; In the formula, R １２ , R １２’ , and R １２’’ H and C are independent of each other. １ -C ８ Alkyl; C ２ -C ８ Heteroalkyl, alkylcycloalkyl, heterocycloalkyl; C ３ -C ８ a Lille, Ar-alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcyclo Alkyl, alkylcarbonyl, heteroaryl; or esters having 1 to 8 carbon atoms, -tel or amide; or formula (OCH ２ CH ２ ) ｐ Or (OCH ２ CH (CH ３ )) ｐ Polyethylene oxy units (p is an integer from 0 to approximately 1000), or combinations of the above. Either selected from the available options, or none exist; X is S, O, NH, SO, SO ２ , or CH ２ It is; m' is either 0 or 1.

2. Side-chain conjugated compounds of formula (III): 【Transformation 8】 In the formula, D, W, w, L １ , L ２ Q １ Q ２ , V １ , V ２ , v １ , v ２ n, T is a claim This is the same definition as in item 1.

3. It can readily react with cell-binding molecule T to form a conjugate of formula (I), and formula (IV ) Side-chain linked compounds: 【Chemistry 9】 During the ceremony, D, W, w, L １ , L ２ Q １ Q ２ , V １ , V ２ , v １ , v ２ , and n are as per claim 1 This is the same definition; Lv １ These are thiols, amines, carboxylic acids, selenols, and phenols on cell-binding molecules. It is a reactive group that can react with a hydroxyl group. Lv １ is OH; F; Cl; Br; I ; Nitrophenol; N-hydroxysuccinimide (NHS); Phenol; Dinitro Phenol; pentafluorophenol; tetrafluorophenol; difluorophenol Imidazole; monofluorophenol; pentachlorophenol; triflate; imidazole Dichlorophenol; Tetrachlorophenol; 1-Hydroxybenzotriazole; Tosylate; Mesylate; 2-ethyl-5-phenylisoxazolium-3'-sulfone , self-formed, or combined with other anhydrides, such as acetic anhydride or formic anhydride. Anhydrous formed in; or for peptide coupling reactions, or for Mitsunobu reactions The intermediate molecule is selected from the intermediate molecules produced by the condensation reagent for EDC. (N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide), DCC (disyl Chlohexylcarbodiimide, N,N'-diisopropylcarbodiimide (DIC) N-cyclohexyl-N'-(2-morpholinoethyl)carbodiimide meso-p-tolu Ensulfonate (CMC, or CME-CDI), 1,1'-carbonyldiimidazo Lu (CDI), TBTU (O-(benzotriazole-1-yl)-N,N,N',N' -Tetramethyluronium tetrafluoroborate), N,N,N',N'-Tetramethyl LU-O-(1H-benzotriazole-1-yl)uronium hexafluorophosph (HBTU), (benzotriazole-1-yloxy)tris(dimethylamino) Suphonium hexafluorophosphate (BOP), (benzotriazole-1-ylo Tripyrrolidinophosphonium hexafluorophosphate (PyBOP), Dietary Lucyanophosphonate (DEPC), chloro-N,N,N',N'-tetramethylform Amidinium hexafluorophosphate, 1-[bis(dimethylamino)methylene]- 1H-1,2,3-Triazolo[4,5-b]pyridinium-3-oxidehexafluor Lophosphat (HATU), 1-[(dimethylamino)(morpholino)methylene]-1 H-[1,2,3]triazolo[4,5-b]pyridine-1-ium-3-oxidehex Safluorophosphate (HDMA), 2-chloro-1,3-dimethylimidazolidinium Muhexafluorophosphate (CIP), chlorotripyrrolidinophosphonium hexaf Luolophosphate (PyClOP), fluoro-N,N,N',N'-bis(tetramethyl) Thiene)formamidinium hexafluorophosphate (BTFFH), N,N,N' N'-tetramethyl-S-(1-oxide-2-pyridyl)thiuronium hexafluor Lophosphate, O-(2-oxo-1(2H)pyridyl)-N,N,N',N'-teto Lamethylthiuronium tetrafluoroborate (TPTU), S-(1-oxide-2- Pyridyl)-N,N,N',N'-tetramethylthiuronium tetrafluoroborate, O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethylamine Tyluronium hexafluorophosphate (HOTU), (1-cyano-2-ethoxy) -2-Oxoethylideneaminooxy)dimethylamino-morpholino-carbeniumhexyl Safluorophosphat (COMU), O-(benzotriazole-1-yl)-N,N ,N',N'-bis(tetramethylene)uronium hexafluorophosphate (HBP yU), N-benzyl-N'-cyclohexylcarbodiimide (along with polymer bonds, (Ihanashi), dipyrrolidino(N-succinimidyloxy)-carbenium hexafluor Lophosphat (HSPyU), chlorodipyrrolidinocarbenium hexafluorophosph Art (PyCIU), 2-chloro-1,3-dimethylimidazolinium tetrafluoro Borate (CIB), (benzotriazole-1-yloxy)dipiperidinocarbenyl Muhexafluorophosphate (HBPipU), O-(6-chlorobenzotriazole) -1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate ( TCTU), bromotris(dimethylamino)phosphonium hexafluorophosphate (BrP), propylphosphonic anhydride (PPACA, T3P®), 2-Mo Ruhorinoethyl isocyanide (MEI), N,N,N',N'-tetramethyl-O-(N - succinimidyl) uronium hexafluorophosphate (HSTU), 2-bromo -1-ethylpyridinium tetrafluoroborate (BEP), O-[(ethoxycal [Bonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetra Fluoroborate (TOTU), 4-(4,6-dimethoxy-1,3,5-triazine- 2-yl)-4-methylmorpholinium chloride (MMTM, DMTMM), N,N,N ',N'-tetramethyl-O-(N-succinimidyl)uroniumtetrafluorobore (TSTU), O-(3,4-dihydro-4-oxo-1,2,3-benzotriazine) N-3-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TDBTU), 1,1'-(azodicarbonyl)dipiperidine (ADD), di-(4- Chlorobenzyl azodicarboxylate (DCAD), di-tert-butyl azodicarboxylate Luboxylate (DBAD), diisopropyl azodicarboxylate (DIAD), di Selected from ethyl azodicarboxylate (DEAD). Lv １ This is due to the acid itself or other C １ ~C ８ Anhydrous substances formed by anhydrous substances are also acceptable; Lv １ Preferably, Select from below: 【Chemistry 10】 【change】 In the formula, X １’ is F, Cl, Br, I, or Lv ３ is; X ２’ is O, NH, N(R １ ), or CH ２ is; R ３ H is independently an aromatic, a heteroaromatic, or one or more The H atom independently becomes -R １ -Halogen, -OR １ , -SR １ , -NR １ R ２ , -NO ２ , -S(O)R １ , -S(O) ２ R １ , or -COOR １ Aromatic groups substituted by Yes; Lv ３ F, Cl, Br, I, nitrophenol; N-hydroxysuccinimi (NHS); phenol; dinitrophenol; pentafluorophenol; tetraf Luolophenol; difluorophenol; monofluorophenol; pentachlorophenol Nol; Triflate; Imidazole; Dichlorophenol; Tetrachlorophenol; 1-Hydroxybenzotriazole; Tosylate; Mesylate; 2-Ethyl-5-Phenylate Luisoxazolium-3'-sulfonate, self-formed or other anhydrous, For example, anhydrous formed with acetic anhydride or formic anhydride; or peptide cups Intermediate molecules produced by condensation reagents for ring reactions or Mitsunobu reactions. It is a leaving group that is selected from among them.

4. It can readily react with cell-binding molecule T to form a conjugate of formula (III), formula ( V) Side-chain linked compounds: 【Chemistry 11】 During the ceremony, D, W, w, L １ , L ２ Q １ Q ２ , V １ , V ２ , v １ , v ２ , and n are as per claim 1 This is the same definition; Lv １ and Lv ２ Lv in formula (IV) of claim 3 is independent of Lv １ It has the same definition In equation (V), Lv １ and Lv ２ Both may be the same or different.

5. Side chain Q according to claim 1, 2, 3, or 4 １ and Q ２ This is from Iq-01 to Iq-35. Selected independently: 【Chemistry 12】 【change】 During the ceremony, R ２５ and R ２５’ These are independently H;HC(O), CH ３ C(O), CH ３ C (NH) NH-(C) １ -C １８ ) Alkyl, C(O)NH-(C １ -C １８ ) alkyl, C(O ) - (C １ -C １８ ) Alkyl, C １ -C １８ Alkyl, C １ -C １８ Alkyl, Alky Lou-Y １ -SO ３ H, C １ -C １８ Alkyl-Y １ -PO ３ H ２ , C １ -C １８ Alkyl -Y １ -CO ２ H, C １ -C １８ Alkyl-Y １ -N ＋ R １２ R １３ R １３’ R １４ , C １ -C １８ Alkyl-Y １ -CONH ２ , C ２ -C １８ Alkylene, C ２ -C １８ Esthetician Ru, C ２ -C １８ Ether, C ２ -C １８ Amine, C ２ -C １８ Alkylcarboxyl Mido, C ３ -C １８ Ariel, C ３ -C １８ Cyclic alkyl, C ３ -C １８ Complex algebras, 1-2 4 amino acids; C ２ -C １８ lipid, C ２ -C １８ fatty acids, or C ２ -C １８ Fat ammonium Selected from lipids; X １ and X ２ These are independently NH, N(R1'), O, CH ２ , S, C(O), S(O) , S (O ２ ), P(O)(OH), NHNH, CH=CH, Ar, or (Aa)q １ from Selected, q １ = 0 to 24 (0 to 24 amino acids, q １ (=0 means absence); X １ , X ２ , X ３ , X ４ , Y １ , Y ２ , and Y ３ These are independently NH, N(R) １ '), O 、C(O)、CH ２ 、S, S(O), NHNH, C(O), OC(O), OC(O)O, OC(O)NH, NHC(O)NH, Ar or Ar or (Aa)Q １ Selected from, X １ , X ２ , X ３ , X ４ , Y １ , Y ２ , and Y ３ It is independent and does not need to exist; p １ , p ２ , and p ３ Independently, they range from 0 to 100, but are not simultaneously 0; q １ , q ２ , and q ３ These range independently from 0 to 24; R １２ , R １３ , R １３’ , and R １４’ H and C are independent of each other. １ -C ６ From alkyl Selected; Aa is a natural or unnatural amino acid; Ar or (Aa)x １ These are identical or different sequences of peptides, and q １ = 0 is (Aa) q １ It means that there is nothing.

6. The D (amanita toxin structure) described in claim 1, 2, 3, or 4 is IIa, IIb, II c, II-01, II-02, II-03, II-04, II-05, II-06, II -07, II-08, II-09, II-10, II-11, II-12, II-13, II-14, II-15, II-16, II-17, II-18, II-19, II-2 0, II-21, II-22, II-23, II-24, II-25, II-26, or Isotopes of one or more chemical elements, pharmaceutically acceptable salts, hydrates, and hydrated salts; compounds of these elements. Polymorphic crystalline structure; or optical isomers, racemates, diastereomers, or enantiomers. Selected from: 【Chemistry 13】 【change】 【change】 【change】 【change】 【change】 【change】 During the ceremony, Z ２ is oxygen or a lone pair of electrons; R １５ H, NHR １２ , OR １２ , C １ -C ８ Linear or branched alkyl or hetero Alkyl; C ２ -C ８ Linear or branched alkenyl, alkynyl, alkylcycloalkyl , heterocycloalkyl; C ３ -C ８ Linear or branched aryl, Ar-alkyl, complex Cyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl , heteroaryl; carbonate (-R １ C(O)OR １２ ), carbamate (-R １２ C(O)NR １２’ R １３ ); or carboxylates, esters, ethers having 1 to 8 carbon atoms, or amide; or 1 to 8 amino acids; or formula (OCH ２ CH ２ ) ｐ Or (OCH ２ CH (CH ３ )) ｐ Polyethylene oxy units having (p is an integer from 0 to approximately 1000) It is; Z １ is H, O, S, NH, NHNH, or R １２ It is either true or not true; R ２１ COR １２ , NHCOR １２ COOR １２ CONHR １２ , R １２ , R １２ It is NH; R ２２ R １２ , SR １２ , SCH(CH ３ ) R １２ SC (CH ３ ) ２ R １２ dea ru; X is O, S, NH, NHNH, or CH ２ It is; R １ 、R ２ 、R ３ 、R ４ 、R ５ 、R ６ 、R ７ 、R ８ 、R ９ 、R １０ 、R １１ 、R １２ 、 R １２’ , R １３ , and X １ This is the same definition as above.

7. W, L according to claim 1, 2, 3, or 4 １ , L ２ , V １ , and V ２ They are independent, 1 or less The following linked components may be included: 【Chemistry 14】 【change】 【change】 During the ceremony, 【Chemistry 15】 This is a binding site; X ２ , X ３ , X ４ , X ５ , or X ６ These are independently NH;NHNH;N(R １２ ); N( R １２ )N(R １２’ ) ; O ; S ; C １ -C ６ Alkyl; C ２ -C ６ Heteroalkyl, A Lucylcycloalkyl, heterocycloalkyl; C ３ -C ８ Aryl, Ar-alkyl, Heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkylcarbonyl , heteroaryl; or selected from 1 to 8 amino acids; Here, R １２ and R １２’ H;C １ -C ８ Alkyl; C ２ -C ８ hetero Alkyl, alkylcycloalkyl, heterocycloalkyl; C ３ -C ８ Aryl, Ar - Alkyl, heterocyclic, carbocyclic, cycloalkyl, heteroalkylcycloalkyl, alkyl Carbonyl, heteroaryl; or esters, ethers, or ammonium compounds having 1 to 8 carbon atoms. Do; or formula (OCH ２ CH ２ ) ｐ Or (OCH ２ CH (CH ３ )) ｐ Poly Telenoxy units (where p is an integer from 0 to approximately 1000); or combinations thereof. That is the case.

8. W, L according to claim 1, 2, 3, or 4 １ , L ２ , V １ , and V ２ The following are independent of the above: Includes: (A): Self-destructing component, peptide unit, hydrazone bond, disulfide, ester, oxy A shim, amide, or thioether bond. The aforementioned self-destructing unit contains 2-aminoimidazo Lu-5-methanol derivatives, heterocyclic PAB analogs, β-glucuronides, and o- or p- - The electronic structure of aminobenzyl acetals, etc. is similar to that of para-aminobenzylcarbamoyl (PAB). Aromatic compounds similar to the group; or any one of the following structures: 【Chemistry 16】 In the formula, ( ＊ ) Atoms are additional spacers or releaseable linked units, cytotoxic agents, and / or the binding site of the binding molecule (CBA); X １ , Y １ Z ２ , and Z ３ Independent , NH, O, or S; Z １ H and NHR are independent. １ , OR １ , SR １ COX １ R １ And here X １ and R １ The definition is as above; v is 0 or 1; U １ teeth Independently, H, OH, C １ ~C ６ Alkyl, (OCH ２ CH ２ ) ｎ , F, Cl, Br, I 、OR ５ 、SR ５ 、NR ５ R ５ ’、N=NR ５ 、N=R ５ 、NR ５ R ５ ’、NO ２ 、SO R ５ R ５ ’、SO ２ R ５ 、SO ３ R ５ 、OSO ３ R ５ 、PR ５ R ５ ’、POR ５ R ５ ’、 PO ２ R ５ R ５ ’, OPO (OR ５ )(OR ５ ’), or OCH ２ PO (OR ５ (OR ５ ')) and here, R ５ and R ５ ' is independent of H, C １ ~C ８ Alkyl; C ２ ~C ８ Alkenyl, alkynyl, heteroalkyl, or amino acid; C ３ ~C ８ Aryl, complex Cyclic, carbocyclic, cycloalkyl, heterocycloalkyl, heteroaralkyl, alkyl Selected from carbonyl or glycoside; or medicinal cationic salt; (B): Non-destructible conjugate component containing one of the following structures: 【Chemistry 17】 【change】 In the formula, ( ＊ Atoms labeled with ) are bond points; X １ , Y １ , U １ , R ５ and R ５’ of The definition is as stated above; r is between 0 and 100; m and n are independently between 0 and 20; (C): At least one bond that can break down under physiological conditions; pH instability, acid Instability, basic instability, oxidative instability, metabolic instability, biochemical instability, or enzyme A releaseable linkage containing an unstable bond and having one of the following structures: -(CR １５ R １６ ) ｍ (A) ｒ (CR) １７ R １８ ) ｎ (OCH) ２ CH ２ ) ｔ -、-(CR １５ R １ ６ ) ｍ (CR) １７ R １８ ) ｎ (A) ｒ (OCH) ２ CH ２ ) ｔ -、-(A]) ｒ -(CR) １５ R １６ ) ｍ (CR) １７ R １８ ) ｎ (OCH) ２ CH ２ ) ｔ -、-(CR １５ R １６ ) ｍ (CR) １７ R １８ ) ｎ (OCH) ２ CH ２ ) ｒ (A) ｔ -、-(CR １５ R １６ ) ｍ (C) R １７ =R １８ )(CR １９ R ２０ ) ｎ (A) ｔ (OCH) ２ CH ２ ) ｒ -、-(CR １ ５ R １６ ) ｍ (NR) １１ COON ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ - 、-(CR １５ R １６ ) ｍ (A) ｔ (NR) ２１ CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-(CR １５ R １６ ) ｍ (OCO)(Aa) ｔ (CR １９ R ２０ ) ｎ (O CH ２ CH ２ ) ｒ -、-(CR １５ R １６ ) ｍ (OCNR １７ )(Aa) ｔ (CR １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-(CR １５ R １６ ) ｍ (C) (A) ｔ -(CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-(CR １５ R １６ ) ｍ (NR) ２１ CON) ) ｔ (CR １９ R ２０ ) ｎ (OCH ２ CH ２ ) ｒ -、-(CR １５ R １６ ) ｍ (O. )(Aa) ｔ (CR) １９ R ２０ ) ｎ -(OCH ２ CH ２ ) ｒ -、-(CR １５ R １６ ) ｍ (OCNR) １７ )(Aa) ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-(CR １ ５ R １６ ) ｍ (C) (A) ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-(C R １５ R １６ ) ｍ -phenyl-(CO)(Aa) ｔ (CR １７ R １８ ) ｎ -, - (CR １ ５ R １６ ) ｍ -furyl-(CO)(Aa) ｔ (CR １７ R １８ ) ｎ -, -(CR １５ R １ ６ ) ｍ -Oxazolyl-(CO)(Aa) ｔ (CR １７ R １８ ) ｎ -, - (CR １５ R １ ６ ) ｍ - Thiazolyl - (CO) (Aa) ｔ (CCR １７ R １８ ) ｎ -, - (CR １５ R １ ６ ) ｔ -Thenyl-(CO)(CR １７ R １８ ) ｎ -, - (CR １５ R １６ ) ｔ - Imida Zolyl-(CO)(CR １７ R １８ ) ｎ -, - (CR １５ R １６ ) ｔ - Morpholino - (C O) (Aa) ｔ (CR １７ R １８ ) ｎ -, - (CR １５ R １６ ) ｔ -Piperadino- (CO ) (Aa) ｔ (CR １７ R １８ ) ｎ -, - (CR １５ R １６ ) ｔ -N-methylpiperazine -(3O)(Aa) ｔ (32) １７ 2 １８ ) ) ｎ -、-(32 １５ 2 １６ ) ) ｍ -(Aa) ｔ フ Enyl-,-(CR １５ R １６ ) ｍ - (Aa) ｔ Frills -, - (CR １５ R １６ ) ｍ - O Xazolyl (Aa) ｔ -, - (CR １５ R １６ ) ｍ - Thiazolyl (Aa) ｔ -, - (CR １５ R １６ ) ｍ - Thienil (Aa) ｔ -, - (CR １５ R １６ ) ｍ -Imidazolyl (Aa ) ｔ -, - (CR １５ R １６ ) ｍ - Morpholino - (Aa) ｔ -, - (CR １５ R １６ ) ｍ -Piperadino- (Aa) ｔ -, - (CR １５ R １６ ) ｍ -N-methylpiperazino-(Aa ) ｔ -、-K(CR １５ R １６ ) ｍ (A) ｒ (CR) １７ R １８ ) ｎ (OCH) ２ CH ２ ) ｔ -、-K(CR １５ R １６ ) ｍ (CR) １７ R １８ ) ｎ (A) ｒ (OCH) ２ CH ２ ) ｔ -、-K(Aa) ｒ (CR) １５ R １６ ) ｍ (CR) １７ R １８ ) ｎ (OCH) ２ CH ２ ) ｔ - ,-K(CR １５ R １６ ) ｍ (CR) １７ R １８ ) ｎ (OCH) ２ CH ２ ) ｒ (A) ｔ -、 -K(CR １５ R １６ ) ｍ (CR １７ =R １８ )(CR １９ R ２０ ) ｎ (Aa) ｔ (OC H ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (NR １１ CO)(Aa) ｔ (CR １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR ５ R ６ ) ｍ (A) ｔ (NR) ２１ CO)( CR １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (OCO)(A (a) ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (OC) NR １７ )(Aa) ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (C) (A) ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (NR) ２１ COON ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (O) (A) ｔ (CR) １９ R ２０ ) ｎ (OCH) ２ C H ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (OCNR １７ )(Aa) ｔ (CR １９ R ２０ ) ｎ (OCH) ２ CH ２ ) ｒ -、-K(CR １５ R １６ ) ｍ (C) (A) ｔ (CR) １９ R ２０ ) ｎ (OCH ２ CH ２ ) ｒ -, -K (CR １５ R １６ ) ｍ -phenyl-(CO)(A a) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｍ -Frill- (CO) (Aa) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｍ -Oxazolyl-(CO)(Aa ) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｍ - Thiazolyl - (CO) (Aa ) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｔ -Thenyl-(CO)(CR １ ７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｔ -Imidazolyl-(CO)(CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｔ - Morphorino - (CO) (Aa) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｔ -Piperadino-(CO)(Aa) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｔ -N-methylpiperazine-(CO)(Aa) ｔ (CR １７ R １８ ) ｎ -, -K (CR １５ R １６ ) ｍ - (Aa) ｔ Phenyl-,-K (CR １５ R １６ ) ｍ - (Aa) ｔ Frill-,-K (CR １５ R １６ ) ｍ -Oxazolyl (Aa) ｔ -, -K (CR １５ R １６ ) ｍ - Thiazolyl (Aa) ｔ -, -K (CR １５ R １６ ) ｍ - Thenil (Aa) ｔ -, -K (CR １５ R １６ ) ｍ - Imidazolyl (Aa) ｔ -, -K ( CR １５ R １６ ) ｍ - Morpholino - (Aa) ｔ -, -K (CR １５ R １６ ) ｍ - Piperaji ノ-(Aa) ｔ G-、-K(CR ５ R ６ ) ｍ -N-methylpiperazino-(Aa) ｔ -; In the formula, m, Aa, m, n, R １３ , R １４ , and R １５ The definition is as above; t and r are independently between 0 and 100; R １６ , R １７ , R １８ , R １９ , and R ２０ H; halide; C １ ~C ８ Alkyl; C ２ ~C ８ Aryl, alkenyl, alkynyl, ether, ester, amine , or an amide, and one or more halides, CN, NR １２ R １２’ CF ３ , OR １ ２ aryl, heterocyclic ring, S(O)R １２ SO ２ R １２ , -CO ２ H, -SO ３ H, -O R １２ , -CO ２ R １２ , -CONR １２ , -PO ２ R １２ R １２ , -PO ３ H, or P (O)R １２ R １２’ R １３ Selected from those arbitrarily substituted; K is NR １２ , -SS-, -C(=O)-, -C(=O)NH-, -C(=O)O-, -C=NH-O -, -C=N-NH-, -C(=O)NH-NH-, O, S, Se, B, Het (complex ring) or C ３ ~C １２ It is a peptide containing a heteroaromatic ring (or 1 to 20 amino acids).

9. The following a-01 to a-40, 78a to c, 91, 95, 97, 114, 117, 12 ６、１３２、１４６、１５４、１６７、１７９、１８１、１９７、１９８、２０６、２４ A conjugate of formula (I) according to claim 1, having the structure of 7, 250, 258, 260, 262 Compounds, or isotopes of one or more chemical elements, pharmaceutically acceptable salts, hydrates, etc. or hydrated salts; or polymorphic crystalline structures of these compounds; or optical isomers, racemates, di Astereomers, or enantiomers: [Chemistry 18] 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 In the formula, X ８ is O, S, NH, NHNH, NHR １２ , SR １２ SSR １２ , SSCH (CH ３ ) R １２ , SSC (CH ３ ) ２ R １２ , or R １２ It is; m １ The range is 0 to 20. ru; X １ , X ２ , X ３ , X ４ , X ５ , p １ , p ２ , q １ , q ２ , m, n, R ２５ , and m Ab is the same as above; Aa is a natural or unnatural amino acid; r is between 0 and 100. If r > 2, then (Aa)r is a peptide containing the same or different amino acid sequences; r = 0 means that (Aa)r does not exist.

10. The structure described in claim 2, having the following structures b-01 to b-22, 216, 221, and 240. A conjugated compound of formula (III), or an isotope of one or more chemical elements, pharmaceutically acceptable Salts, hydrates, or hydrated salts of these compounds; or polymorphic crystalline structures of these compounds; or optical Isomers, racemates, diastereomers, or enantiomers: 【Chemistry 19】 【change】 【change】 【change】 【change】 【change】 In the formula, X ８ is O, S, NH, NHNH, NHR １２ , SR １２ SSR １２ , SSCH (CH ３ ) R １２ , SSC (CH ３ ) ２ R １２ , or R １２ is; X １ , X ２ , X ３ , X ４ 、X ５ 、R １２ 、R １２’ 、R １３ 、R １３’ 、R ２５ 、R ２５’ 、p １ 、p ２ 、q １ , q ２ , m, m １ n and mAb are the same as above; Aa is a natural or non-natural amino acid. It is an acid; r is between 0 and 12; if r > 2, (Aa)r are the same or different amino acids. It is a peptide containing the sequence; r=0 means that (Aa)r does not exist.

11. The following are c-01 through c-40, 71, 76, 77, 90, 94, 96, 113, and 116. 、１２６、１３１、１４５、１５３、１６６、１７８、１８０、１９５、１９６、２０５ The formula (IV) described in claim 3, having the structure of 246, 249, 257, 259, 261 ) compounds, or isotopes of one or more chemical elements, pharmaceutically acceptable salts, hydrates, or hydrated salts; or polymorphic crystalline structures of these compounds; or optical isomers, racemates, diastereomers, or enantiomers: 【Chemistry 20】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 In the formula, X １ X ２ X ３ X ４ X ５ X ８ Z ２ Z ３ p, p １ p ２ p ３ q １ , q ２ Lv ３ , m, n, R １２ , R １２’ , R ２５ , R ２５’ , (Aa)r, and m Ab is the same as above.

12. The structure described in claim 4, having the following structures d-01 to d-25, 215, 220, and 239. Compounds of formula (V) shown, or isotopes of one or more chemical elements, or pharmaceutically acceptable salts. , hydrates or hydrated salts; or polymorphic crystalline structures of these compounds; or optical isomers, Racemic mixture, diastereomer, or enantiomer: 【Chemistry 21】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 In the formula, X １ X ２ X ３ X ４ X ５ X ８ Z ２ Z ３ p, p １ p ２ p ３ q １ 、q ２ 、Lv １ 、Lv ２ 、Lv ３ 、Lv ３’ 、m、n、R １２ 、R １２’ 、R １５ 、R ２５ , R ２５’ (Aa)r and mAb are the same as above.

13. (A); Antibodies, proteins, probodies, nanobodies, vitamins (including folic acid), Peptides, polymer micelles, liposomes, lipoprotein drug carriers, nanoparticle drug carriers, The above components bound to or coated with dendrimers and cell-binding ligands. A child or particle, or a group consisting of the above combinations; (B); Antibody-like proteins, full-length antibodies (polyclonal antibodies, monoclonal antibodies, Antibody dimers, antibody macromers), multispecific antibodies (bispecific antibodies, triplicity antibodies, or quadruple specific antibodies) Selected from specific antibodies: single-chain antibodies, antibody fragments that bind to target cells, monoclonal antibodies. Monoclonal antibodies, single-chain monoclonal antibodies, monoclonal antibody fragments that bind to target cells, chimeric antibodies Antibody, chimeric antibody fragment that binds to target cells, domain antibody, domain that binds to target cells Antibody fragments, surface-reconstituted antibodies, single-chain surface-reconstituted antibodies, surface-reconstituted antibodies that bind to target cells Antibodies, humanized antibodies, surface-reconstituted humanized antibodies, single-chain humanized antibodies, human antibodies that bind to target cells Antibody fragments, anti-idiotype (anti-Id) antibodies, CDRs, bispecific antibodies, trispecific antibodies Body, four-specific antibodies, mini-antibodies, probody, probody fragment, small immunoprotein (SIP) ), lymphokines, hormones, vitamins, growth factors, colony-stimulating factors, nutrient transport factors, Large molecular weight proteins, fusion proteins, kinase inhibitors, gene targeting agents, nanoparticles, and polymers modified with antibodies or large molecular weight proteins; (C) Cell-binding ligand or receptor agonist selected from the following: folic acid derivative; gluconyl sulfate Urea tamic acid derivatives; somatostatin and its analogues (octreotide (sandostatin) Selected from the group consisting of ) and lanreotide (somatrin). ); aromatic sulfone amino acids D; Pituitary adenylate cyclase-activating peptide (PACAP) (PAC1); Vasoactive Sexual intestinal peptides (VIP / PACAP) (VPAC1, VPAC2); melanocyte stimulation Hormones (α-MSH); cholecystokinin (CCK) / gastrin receptor agonists; Bombesin (Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2 Consists of (Selected from the group consisting of gastrin-releasing peptides (GRPs).) Neurotensin receptor ligands (NTR1, NTR2, NTR3); Substance P (NK1 receptor) ligand; neuropeptide Y (Y1-Y6); RGD (Arg-Gly-Asp) ), NGR (Asn-Gly-Arg), dimer and polymeric cyclic RGD peptide (from cRGDfVc) Selected.), TAASGVRSMH and LTLRWVGLMS (chondroitin sulfate) Homing peptides containing proteoglycan NG2 receptor ligand and F3 peptide; Cell-permeable peptides (CPPs); luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, as well as gonadotropin-releasing hormone (GnRH) agonists Selected from the following groups, testosterone production, as well as follicle-stimulating hormone (FSH) and Buserelin (Pyr-His- Trp-Ser-Tyr-D-Ser(OtBu)-Leu-Arg-Pro-NHEt, gonadrelin (Pyr-His-Trp-Ser-Tyr-Gl y-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-NH) Et), leuprolide (Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt), nafrerin (Py r-His-Trp-Ser-Tyr-2Nal-Leu-Arg-Pro-Gly-NH 2 ), Triptorelin (Pyr-His-Trp-Ser-Ty rD-Trp-Leu-Arg-Pro-Gly-NH 2 ), Nafarelin, Deslorerin, Abarerix (Ac-D-2 Nal-D-4-chloroPhe-D-3-(3-pyridyl)Ala-Ser-(N-Me)Tyr-D-Asn-Leu-isopropyl-Pro-D Ala-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-Phe Lysyl)Ala-Ser-4-amioPhe(L-hydroorotyl)-D-4-amioPhe(carbamoyl)-Leu-isop Ropil Lys-Pro-D-Ala-NH 2 ), and Ganirelix (Ac-D-2Nal-D-4-chloroPhe-D-3-(3-Phe- Lysyl)Ala-Ser-Tyr-D-(N9,N10-diethyl)-homoArg-Leu-(N9,N10-diethyl)-homoArg-P ro-D-Ala-NH 2 Peptide hormones selected from the group consisting of ); Toll-like receptors (TLRs) Selected from the group consisting of ligands, C-type lectins, and Nod-like receptor (NLRs) ligands. Selected pattern recognition receptors (PRRs); calcitonin receptor agonists; integrating α receptors and their 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 Selected from the group consisting of ( ) Agonist ( 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-)(ciliate) )]; nanobody (derivative of VHH (camel Ig)); domain antibody (dAb, VH or VL domain derivatives), bispecific T cell induction (Bite, bispecific antibody); double parent Japanese retargeting (DART, bispecific antibody); tetravalent tandem antibody (TandA b. Dimerized bispecific antibody); anticarin (a derivative of lipocalin); adnectin (the FN3 (fibronectin) 10th; designed ankyrin repeat protein (DA RPins; avimer; EGF receptor and VEGF receptor agonist ； (D): Small molecules of cell-binding molecules / ligands or cell receptor agonis selected from the following. T: LB01 (folic acid), LB02 (PMSA ligand), LB03, represented by the following structures (PMSA ligand), LB04 (PMSA ligand), LB05 (somatostatin), LB06 (somatostatin), LB07 (octreotide, somatostatin analog), L B08 (lamaleotide, somatostatin analog), LB09 (bapreotide (Sambar)) (somatostatin analog), LB10 (CAIX ligand), LB11 (CAIX ligand) LB12 (Gastrin-releasing peptide receptor (GRPr), MBA), LB13 (Yellow Body-forming hormone-releasing hormone (LH-RH) ligand and GnRH), LB14 (corpus luteum form) Hormone-releasing hormone (LH-RH) and GnRH ligand), LB15 (GnRH ligand) Intagonist, Abalerix), LB16 (cobalamin, vitamin B12 analog), L B17 (cobalamin, vitamin B12 analog), LB18 (α ｖ β ３ Integrin receptors (for cyclic RGD pentapeptide), LB19 (heterodivalent for VEGF receptor) Peptide ligands), LB20 (neuromedin B), LB21 (G protein-coupled receptors) Bombecin for the body), LB22 (TLR for Toll-like receptors) ２ ), LB23 (A (for endogen receptors), LB24 (α ｖ Silengitide for integrin receptors (Cilengide) / Cyclo(-RGDfV-), LB23 (Fuldrocortisol) n), LB25 (rifabutin analog), LB26 (rifabutin analog), LB27 ( Rifabutin analogs), LB28 (fludrocortisone), LB29 (dexamethasone) LB30 (fluticasone propionate), LB31 (beclomethasone dipropionate) LB32 (triamcinolone acetonide), LB33 (prednisone), LB34 (prednisone) Rednisolone), LB35 (methylprednisolone), LB36 (betamethasone), LB 37 (irinotecan analog), LB38 (crizotinib analog), LB39 (bortezomi (Carfilzomib analogs), LB40 (carfilzomib analogs), LB41 (Carfilzomib analogue), LB42 (Leuprolide analogue), LB43 (Trypto Relin analogs), LB44 (clindamycin), LB45 (liraglutide analog), L B46 (semaglutide analog), LB47 (letapamrin analog), LB48 (indib Phosphorus analogs), LB49 (vinblastine analog), LB50 (lixisenatide analog) LB51 (osimertinib analog), LB52 (nucleoside analog), LB53 (e Lulotinib analogues), or LB54 (lapatinib analogues); 【Chemistry 22】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 【change】 During the ceremony, 【Chemistry 23】 This is the connection point with the side chain connector of this patent; X ４ and Y １ These are O, NH, and NHN, which are independent of each other. H, NR １ 、S、C(O)O,C(O)NH,OC(O)NH,OC(O)O,NHC( O)NH、NHC(O)S、OC(O)N(R １ )、N(R １ )C(O)N(R １ )、C H ２ , C(O)NHNHC(O), and C(O)NR １ is; X ５ H, CH ３ F, or Cl; M １ and M ２ These are independently H, Na, K, Ca, Mg, NH ４ , N(R １２ R １２’ R １３ R １３’ ) is; R １２ , R １２’ , R １３ , and R １３’ Claim This is the same definition as in 1.

14. The cell-binding molecule T according to claim 1, 2, or 13 is a molecule in which T is V of formulas (I) and (III). １ and / or V ２ When connected to, or V of formulas (I) and (III) １ and / or is V ２ It does not exist, and T is L １ and / or L ２ When directly connecting, the following connection structure Having one or more of the following: 【Chemistry 24】 【change】 In the formula, R ２０ and R ２１ C is independent １ ~C ８ Alkyl; C ２ ~C ８ Heteroalkyl , or a complex ring; C ３ ~C ８ Aryl, Ar-alkyl, cycloalkyl, alkyl Cycloalkyl, heterocycloalkyl, heteroalkylcycloalkyl, carbocyclic, young or alkylcarbonyl; or (CH ２ CH ２ O) ｐ C has the formula ２ -C １００ Poly It is ethylene glycol.

15. The cell-binding agent / molecule according to claim 1, 2, 9, or 10 is effective against tumor cells, virus-infected cells, and other similar cells. Cells, microbially infected cells, parasite-infected cells, autoimmune disease cells, activated tumor cells, bone marrow cells, Activated T cells, affected B cells, melanocytes, or the following antigens or receptors Any cell expressing any one of the following can be targeted: CD1, CD1a, CD 1b, CD1c, CD1d, CD1e, CD2, CD3, CD3d, CD3e, CD3g , CD4, CD5, CD6, CD7, CD8, CD8a, CD8b, CD9, CD10, CD11a, CD11b, CD11c, CD11d, CD12w, CD14, CD15, CD16, CD16a, CD16b, CDw17, CD18, CD19, CD20, CD 21, CD22, CD23, CD24, CD25, CD26, CD27, CD28, CD 29, CD30, CD31, CD32, CD32a, CD32b, CD33, CD34, CD35, CD36, CD37, CD38, CD39, CD40, CD41, CD42, CD42a, CD42b, CD42c, CD42d, CD43, CD44, CD45, C D46, CD47, CD48, CD49b, CD49c, CD49c, CD49d, CD 49f, CD50, CD51, CD52, CD53, CD54, CD55, CD56, C D57, CD58, CD59, CD60, CD60a, CD60b, CD60c, CD6 1, CD62E, CD62L, CD62P, CD63, CD64, CD65, CD65s , CD66, CD66a, CD66b, CD66c, CD66d, CD66e, CD66 f, CD67, CD68, CD69, CD70, CD71, CD72, CD73, CD7 4, CD75, CD75s, CD76, CD77, CD78, CD79, CD79a, C D79b, CD80, CD81, CD82, CD83, CD84, CD85, CD85a , CD85b, CD85c, CD85d, CD85e, CD85f, CD85g, CD8 5g, CD85i, CD85j, CD85k, CD85m, CD86, CD87, CD8 8, CD89, CD90, CD91, CD92, CD93, CD94, CD95, CD9 6、CD97、CD98、CD99、CD100、CD101、CD102、CD103 、CD104、CD105、CD106、CD107、CD107a、CD107b、C D108、CD109、CD110、CD111、CD112、CD113、CD114 、CD115、CD116、CD117、CD118、CD119、CD120、CD1 20a、CD120b、CD121、CD121a、CD121b、CD122、CD1 23、CD123a、CD124、CD125、CD126、CD127、CD128、 CD129、CD130、CD131、CD132、CD133、CD134、CD13 5、CD136、CD137、CD138、CD139、CD140、CD140a、C D140b、CD141、CD142、CD143、CD144、CD145、CDw1 45、CD146、CD147、CD148、CD149、CD150、CD151、C D152、CD153、CD154、CD155、CD156、CD156a、CD15 6b、CD156c、CD156d、CD157、CD158、CD158a、CD15 8b1、CD158b2、CD158c、CD158d、CD158e1、CD158e 2、CD158f2、CD158g、CD158h、CD158i、CD158j、CD 158k、CD159、CD159a、CD159b、CD159c、CD160、CD 161、CD162、CD163、CD164、CD165、CD166、CD167、 CD167a、CD167b、CD168、CD169、CD170、CD171、CD 172、CD172a、CD172b、CD172g、CD173、CD174、CD1 75、CD175s、CD176、CD177、CD178、CD179、CD179a 、CD179b、CD180、CD181、CD182、CD183、CD184、CD 185、CD186、CDw186、CD187、CD188、CD189、CD190 、CD191、CD192、CD193、CD194、CD195、CD196、CD1 97、CD198、CD199、CDw198、CDw199、CD200、CD201 、CD202、CD202(a,b)、CD203、CD203c、CD204、CD2 05、CD206、CD207、CD208、CD209、CD210、CDw210a 、㼣㼤㽗㼒㼑㼐㽂、㼣㼤㼒㼑㼑、㼣㼤㼒㼑㼒、㼣㼤㼒㼑㼓、㼣㼤㼒㼑㼓㽁㼑、㼣㼤㼒㼑㼓 a2、CD214、CD215、CD216、CD217、CD218、CD218a� CD218、CD21b9、CD220、CD221、CD222、CD223、CD2 24、CD225、CD226、CD227 、CD228、CD229、CD230、C D231、CD232、CD233、CD234、CD235、CD235a、CD23 5b、CD236、CD237、CD238、CD239、CD240、CD240ce 、CD240d、CD241、CD242、 CD243、CD244、CD245、CD 246, CD247, CD248, CD249, CD250, CD251, CD252 CD253、CD254、CD255、CD 256、CD257、CD258、CD25 9、CD260、CD261、CD262、 CD263、CD264、CD265、CD 266、CD267、CD268、CD269、CD270、CD271、CD272、 CD273、CD274、CD275、CD276、CD277、CD278、CD27 9、CD281、CD282、CD283、 CD284、CD285、CD286、CD 287, CD288, CD289, CD290, CD291, CD292, CD293 CD294、CD295、CD296、CD297、CD298、CD299、CD30 0、CD300a、CD300b、CD30 0c、CD301、CD302、CD303 、CD304、CD305、CD306、C D307、CD307a、CD307b、C D307c、CD307d、CD307e、 CD307f、CD308、CD309、C D310、CD311、CD312、CD3 13、CD314、CD315、CD316 、㼣㼤㼓㼑㼗、㼣㼤㼓㼑㼘、㼣㼤㼓㼑㼙、㼣㼤㼓㼒㼐、㼣㼤㼓㼒㼑、㼣㼤㼓㼒㼒、㼣㼤㼓 23、CD324、CD325、CD326 、CD327、CD328、CD329、C D330、CD331、CD332、CD333、CD334、CD335、CD336 、㼣㼤㼓㼓㼗、㼣㼤㼓㼓㼘、㼣㼤㼓㼓㼙、㼣㼤㼓㼔㼐、㼣㼤㼓㼔㼑、㼣㼤㼓㼔㼒、㼣㼤㼓 43、CD344、CD345、CD346 、CD347、CD348、CD349、C D350、CD351、CD352、CD353、CD354、CD355、CD356 , CD357, CD358, CD359, CD360, CD361, CD362, CD3 63, CD364, CD365, CD366, CD367, CD368, CD369, C D370, CD371, CD372, CD373, CD374, CD375, CD376 , CD377, CD378, CD379, CD381, CD382, CD383, CD3 84, CD385, CD386, CD387, CD388, CD389, CRIPTO, CRIPTO, CR, CR1, CRGF, CRIPTO, CXCR5, LY64, TDG F1, 4-1BB, APO2, ASLG659, BMPR1B, 4-1BB, 5AC, 5 T4 (villi glycoprotein, TPBG, 5T4, Wnt activator inhibitor 1, or WAIF1) ), adenocarcinoma antigen, AGS-5, AGS-22M6, activin receptor-like kinase 1, AFP AKAP-4, ALK, α-integrin, αvβ6, aminopeptidase N, amyloy Beta-β, androgen receptor, angiopoietin 2, angiopoietin 3, annexin A1, Anthrax toxin protective antigen, anti-transferrin receptor, AOC3 (VAP-1), B7-H3, Bacillus anthrax, BAFF (B-cell activating factor), BCMA, B-lymphoma cells, bcr-abl, 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 mo Chief chemokine 11), CCR4 (CC chemokine receptor type 4), CCR5, CD3E (Epsilon), CEA (carcinoembryonic antigen), CEACAM3, CEACAM5 (carcinoembryonic Antigen), CFD (Factor D), Ch4D5, Cholecystokinin 2 (CCK2R), CLDN 18 (Claudin-18), Clamping Factor A, cMet, CRIPTO, FCSF 1R (Colony-Stimulating Factor 1 Receptor), CSF2 (Colony-Stimulating Factor 2, Granulocyte Macrophages) colony-stimulating factor (GM-CSF)), CSP4, CTLA4 (cytotoxic T-lymphoid Sphere-related protein 4), CTAA16.88 tumor antigen, CXCR4, CXC chemokine receptor Form 4, cADP-ribose hydrolase, cyclin B1, CYP1B1, cytomega Lovirus, cytomegalovirus glycoprotein B, dabigatran, DLL4 (delta-like) Ligand 4), DPP4 (Dipeptidyl peptidase 4), DR5 (Death receptor 5) E. coli Shiga toxin type 1, E. coli Shiga toxin type 2, ED-B, EGFL7 (EGF-like domain) Proteins contained: 7), EGFR, EGFRII, EGFRvIII, Endoglin, En Doserin B receptor, endotoxin, EpCAM (epithelial cell adhesion molecule), EphA2, E Pysialin, ERBB2 (Epidermal Growth Factor Receptor 2), ERBB3, ERG (TMPRSS) 2ETS fusion gene), Escherichia coli, ETV6-AML, FAP (fibroblast-activating protein) α-fetoprotein, FCGR1, α-fetoprotein, fibrin II, β-chain, fibronectin External domain B, FOLR (folate receptor), folate receptor α, folate hydrolase, Fos-related RSV F antigen, Frizzled receptor, fucosyl GM1, GD2 ganglioside, G-28 (cell surface glycolipid antigen), GD3 idiotype, Gl oboH, 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), enteric guanylate cyclase Lase, guanylate cyclase-C receptor, thermostable enterotoxin receptor (hSTA) R)), heat shock protein, hemagglutinin, hepatitis B surface antigen, hepatitis B virus, H ER1 (Human Epidermal Growth Factor Receptor 1), HER2, HER2 / neu, HER3 (ERB) B-3), IgG4, HGF / SF (Stem cell growth factor / Cell dispersal factor), HHGFR, H IV-1, histone complex, HLA-DA (human leukocyte antigen), HLA-DR10, HL A-DRB, HMWMAA, human chorionic gonadotropin, NHGF, human cell scattering factor receptor body kinase, HPV E6 / E7, Hsp90, hTERT, ICAM-1 (intercellular Idiotype, IGF1R (IGF-1, insulin-like growth factor 1 receptor) ), IGHE, IFN-γ, influenza hemagglutinin, IgE, IgE Fc region, IGHE, interleukins (IL-1, IL-2, IL-3, IL-4, IL-5, I L-6, IL-6R, IL-7, IL-8, IL-9, IL-10, IL-11, IL- 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), I L-31RA, ILGF2 (insulin-like growth factor 2), integrin (α4, α ＩＩＩ ｂ b ３ ,αvβ3,α ４ b ７ ,α5β1,α6β4,α7β7,αIIβ3,α5β5, αvβ5), interferon-gamma-inducible protein, ITAGA2, ITGB2, KIR2 D, LCK, Le, Regmine, 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, MAG E4, MART1, MCP-1, MIF (macrophage migration inhibitor or glycosylated) Inhibitor (GIF), MS4A1 (Transmembrane 4-domain subfamily A member 1), MSLN (mesothelin), MUC1 (mucin 1, cell surface-related (MUC1) or polymorphism Pediculomycin (PEM), MUC1-KLH, MUC16 (CA125), MCP1 (monocyte) Chemotactic proteins 1), MelanA / MART1, ML-IAP, MPG, MS4A1 (Transmembrane 4-domain subfamily A), MYCN, myelin-related glycoprotein, myo Statins, NA17, NARP-1, NCA-90 (granulocyte antigen), Nectin-4 (AS G-22ME), NGF, neuronal apoptosis-regulating proteinase 1, NOGO-A, No tch receptor, nucleolin, Neu oncogene product, NY-BR-1, NY-ESO-1 OX-40, OxLDL (oxidized low-density lipoprotein), OY-TES1, P21, p 53 non-mutant, P97, Page4, PAP, anti(N-glycolylneuraminic acid) para Tope, PAX3, PAX5, PCSK9, PDCD1 (PD-1, programmed details Platelet death protein 1), PDGF-Rα, (platelet-derived growth factor receptor α), PDGF-R- β, PDL-1, PLAC1, PLAP-like testicular alkaline phosphatase, platelet-derived growth Factor receptor β, sodium phosphate cotransporter, PMEL17, polysialic acid, protein Ze3 (PR1), prostate cancer, PS (phosphatidylserine), prostate cancer cells, Pseudomonas aeruginosa, P SMA, PSA, PSCA, rabies virus glycoprotein, RHD (Rh polypeptide 1) (RhPI), Rhesus factor, RANKL, Ph C, Ras variant, RG55, ROBO4, RS virus, RON, sarcoma metastasis breakpoint Into, SART3, Sclerostine, SLAMF7 (SLAM Family Member 7) Selectin P, SDC1 (Syndecane 1), sLe(a), Somatomedin C, SIP ( Sphingosine-1-phosphate, somatostatin, sperm protein 17, SSX2 STEAP1 (prostate 1 6-transmembrane antigen), STEAP2, STn, TAG-2 2 (tumor-associated glycoprotein 72), survivor, 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 (T Growth-forming 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 Death factor receptor superfamily member 13B), TPBG (trophotrophic membrane glycoprotein), TRAIL-R1 (tumor necrosis apoptosis-inducing ligand receptor 1), TRAIL-R2 (tumor necrosis apoptosis-inducing ligand receptor 1), Bolar death receptor 5 (DR5), major associated calcium signaling transducer 2, MUC Tumor-specific glycosylation of 1, TWEAK receptor, TYRP1 (glycoprotein 75), T RP-2, tyrosinase, VCAM-1, VEGF, VEGF-A, VEGF-2, VE GFR-1, VEGFR2, or vimentin, WT1, XAGE1, or any insulin Cells expressing growth factor receptors, or any epidermal growth factor receptor.

16. The tumor cells described in claim 15 include lymphoma cells, myeloma cells, renal cells, breast cancer cells, prostate cancer cells. Adenocarcinoma 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, testicular cancer cells, malignant cells, or cells that grow and divide at an uncontrolled and rapid pace. A group of cells is selected from which any cells can cleave and cause cancer.

17. A therapeutically effective amount of the conjugate compound according to claim 1, 2, 9, or 10, and a pharmaceutically acceptable A combination of salts, carriers, diluents, or excipients, or conjugates, is included in cancer, autologous A pharmaceutical composition for the treatment or prevention of autoimmune diseases or infectious diseases.

18. By weight, 0.01% to 9% of one or more conjugates according to any one of claims 1, 2, 9, or 10 ９％； One or more polyols in an amount of 0.0% to 20.0%; One or more surfactants in an amount of 0.0% to 2.0%; One or more preservatives in a concentration of 0.0% to 5.0%; One or more amino acids in a concentration of 0.0% to 30%; One or more antioxidants in an amount of 0.0% to 5.0%; One or more metal chelating agents in an amount of 0.0% to 0.3%; One or more buffer salts are added to adjust the pH of the formulation to 4.5 to 7.5, in an amount of 0.0% to 30.0%. ； When reconstituted for administration to patients, the osmotic pressure should be between approximately 250 and 350 mOsm. One or more isotonic agents for adjustment, in an amount of 0.0% to 30.0%; Includes, The aforementioned polyols are fructose, mannose, maltose, lactose, and arabinose. Sucrose, xylose, ribose, rhamnose, galactose, glucose, sucrose, tre Halos, sorbose, melegitose, raffinose, mannitol, xylitol, E Lythritol, Maltitol, Lactitol, Erythritol, Treitol, Sorbitol Selected from glycerol, L-gluconate, or its metal salts; The surfactants mentioned above are polysorbate 20, polysorbate 40, polysorbate 65, Polysorbate 80, Polysorbate 81, or Polysorbate 85, Poloxamer Poly(ethylene oxide)-poly(propylene oxide), polyethylene-polypropylene Len, Triton; sodium dodecyl sulfate (SDS), sodium lauryl sulfate; octi Sodium glucoside; lauryl-, myristyl-, linoleyl-, or stearyl- Lu-sulfobetaine; lauryl-, myristyl-, linoleyl-, or stearyl- Sarcosine; linoleyl-, myristyl-, or cetyl-betaine; lauroamido Ropil-, Cocamidopropyl-, Linoleamidopropyl-, Myristamidopropyl-, Palmidopropyl- or isostearamidopropyl-betaine (lauroamide pro Pills); myristamidopropyl-, palmidopropyl-, or isostearamidopropyl Pyr-dimethylamine; sodium methyl cocoyl taurate or methyl oleyl taurate Disodium urate; dodecyl betaine, dodecyldimethylamine oxide, cocamide Propylbetaine and cocoamphoglycinate; or isostearyl ethylimidonium Muetosulfate; polyethyl glycol, polypropylene glycol, and ethylene Selected from copolymers of propylene glycol; The aforementioned preservatives are benzyl alcohol and octadecyldimethylbenzylammonium chloride. Hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, b Alkyl parabens such as methyl or propylparaben, ethyl and benzyl alcohol, catechins Cole, resorcinol, cyclohexanol, 3-pentanol, or m-cresol Selected from; The aforementioned amino acids are arginine, cystine, glycine, lysine, histidine, and ornithine. From isoleucine, leucine, alanine, glyceryl thamic acid, or aspartic acid Selected; The antioxidant is selected from ascorbic acid, glutathione, cystine, or methionine. To be done; The chelating agent is selected from EDTA or EGTA; The buffer salts mentioned above include citric acid, ascorbic acid, gluconic acid, carbonic acid, tartaric acid, succinic acid, and vinegar. Acids, or sodium, potassium, ammonium, or trihydroxy phthalates. Ethylamino salts; Tris or tromethamine hydrochloride, phosphate or sulfate; Argy Nin, glycine, glycylglycine, or histidine and anionic acetate, chloride, Selected from phosphates, sulfates, or succinates; The isotonic agents mentioned above are mannitol, sorbitol, sodium acetate, potassium chloride, and phosphorus. Select from sodium phosphate, potassium phosphate, trisodium citrate, or sodium chloride. The following is a liquid formulation or a formulated freeze-dried solid / powder as described in claim 17. A listed pharmaceutical composition.

19. In liquid or lyophilized solid form, vials, bottles, pre-filled syringes, or pre The pharmaceutical product according to claim 17 or 18, which is filled into a filled autoinjector syringe. composition.

20. In vitro, in vivo, or ex vivo (e The conjugate according to claim 1, 2, 9, or 10, which has cell-killing activity in x vivo. A body, or the form of the pharmaceutical composition according to claim 17 or 18.

21. Chemotherapy drugs, radiotherapy, immunotherapy drugs, autoimmune disease drugs, anti-infective drugs, or synergistically Other conjugates for treating or preventing cancer, autoimmune diseases, or infectious diseases A pharmaceutical composition according to claim 17 or 18, which is administered at times.

22. The chemotherapeutic agent according to claim 21 is selected from one or more of the following: (1) a) Alkylating agent selected from the following: Nitrogen mustard: Chlorambrane Sil, chlornafadin, cyclophosphamide, dacarbazine, estramustine, ifo Sphamide, Mechloretamine, Mechloretamine Oxide Hydrochloride, Mannomustine, Mitob Lonitol, Melphalan, Mitraktor, Pipobroman, Nobenbitin, Feneste Phosphorus, prednimustine, thiotepa, trophosphamide, uracil mustard; CC-1 065 and synthetic analogues of adzeresin, karzeresin and bizeresin; Duocalmy Syn and its synthetic analogs KW-2189 and CBI-TMI; benzodiazepines Dimers or pyrrolobenzodiazepine (PBD) dimers, tomaimycin dimers, indol Nobenzodiazepine dimer, imidazobenzothiadiazepine dimer, or oxazolidin Benzodiazepine dimers; carmustine, lomustine, chlorozotosine, fotemustine Nitrosourea compounds including nimustine and ranimustine; busulfan, treosulfa Alkyl sulfonates containing , immunosulfan, and biposulfan; triazenes Or dacarbazine; platinum-containing including carboplatin, cisplatin, and oxaliplatin. Compounds; aziridines, benzodopa, carboquan, metsuredopa, and uredopa; eth Lenymines, as well as altoretamine, triethylenemelamine, triethylenephosphorus Mido, triethylenethiophosphoramine, trimethylolomelamamine (trimethylo Methylamemines, including lomelamine; b) Plant alkaloids selected from the following group: vincristine, vinbras Vinca alkaloids including tin, vindesine, vinorelbine, and navelbine; paclitaxel Taxoids including cell and docetaxel, and their analogues; DM1, DM2, DM 3. Meitan containing DM4, DM5, DM6, DM7, meitansine, and anthamitosine. Synoids and their analogues; including the groups cryptophycin 1 and cryptophycin 8. Cryptophycins; epothyrons, erytherobins, discodermolides, brio Statins, drostatins, auristatins, tubulicins, cephalostatins Classes; pancratistatin; sarcodictiin; sponge statin; c) DNA topoisomerase inhibitor selected from the following: 9-aminocamptothecin Camptothecin, cristatol, daunomycin, etoposide, etoposide phosphate, Irinotecan, Mitoxantrone, Novantrone, Retinoic acid (retinols), Teni Epipodof containing Poside, Topotecan, 9-Nitrocamptothecin, or RFS 2000 Ylin compounds; and mitomycin compounds, and their analogues; d) Antimetabolites: {[Antifolic acid: (DHFR inhibitors: methotrexate, trimethotrex Sart, denopterin, pteropterin, aminopterin (4-aminopteroic acid), (or other folic acid analogues); IMP dehydrogenase inhibitors (mycophenolic acid) (including thiazophrine, ribavirin, and EICAR); ribonucleotide reductase inhibitors (Contains hydroxyurea and deferoxamine.) ]; [Pyrimidine analogs: Uracils Related substances (ancitabine, azacitidine, 6-azauridine, capecitabine, carmofur, Cytarabine, dideoxyuridine, doxifluridine, enocitabine, 5-fluoroura Contains cyl, floxuridine, and larcitrexed; cytosine analog: (cytarabine) , containing cytosine arabinoside and fludarabine; purine analogues: (azathiopurine, Contains fludarabine, mercaptopurine, thiamiprine, and thioguanine. Selected from the group consisting of {folic acid supplements such as acids}; e) Hormone therapy agents: Receptor antagonists: [Anti-estrogens: (Megestrol, Laroxine) (Contains cyfen, tamoxifen); LHRH agonists: (goserelin, leup acetate) (including lorid); antiandrogens: (bicalutamide, flutamide, carsterone, propionate) Dromostanorone onate, epithiostanol, goserelin, leuprolide, mepitio Stan, nilutamide, testolactone, trilostane, and other similar androgen inhibitors Contains the agent.)]; Retinoids / deltoid muscle: [Vitamin D3 analogues: (CB1093, EB (Contains 1089, KH1060, cholecalciferol, ergocalciferol); light Linear mechanical therapy agents: (Verteporfin, phthalocyanine, photosensitizer Pc4, demethoxyhir (Contains Pocrelin A); Cytokines: (Interferon α, Interferon γ, Selected from tumor necrosis factor (TNF), including human proteins containing the TNF domain. ru; f) Kinase inhibitors: BIBW2992 (anti-EGFR / Erb2), imatinib, germination Fitinib, pegaptanib, sorafenib, dasatinib, sunitinib, erlotinib, ni Rotinib, lapatinib, axitinib, pazopanib, vandetanib, E7080 (anti-VE) GFR2), mbritinib, ponatinib, bafetinib, bosutinib, cabozantinib, Bismodegib, Iniparib, Ruxolitinib, CYT387, Axitinib, Tivozanib sorafenib, bevacizumab, cetuximab, trastuzumab, ranibizumab, panit Selected from the group consisting of mumab and ispinesive; g) Olaparib, Niraparib, Iniparib, Thalazoparib, Beriparib, CEP97 22 (Cephalon), E7016 (Eisai), BGB-290 (Baygene), or 3 - Poly(ADP-ribose) polymerase selected from the group consisting of aminobenzamides (PARP) inhibitors; h) Endiyne antibiotics (calicheamicin derivatives, calicheamicin γ1, δ1, α 1, or β1; Dynemicin containing dynemicin A and deoxydynemicin; Espera Sewing machine, kedalcidin, C-1027, mazulopeptin, or neocardinostatin chloro Selected from chromophores and related pigment proteins, enediins, and antibiotics. ), acrasinomycin derivatives, actinomycin, anthramycin (autoramycin (in), azacerin, bleomycins, cactinomycin ), carabicin, carminomycin, cardinophilin; chromium Mycins, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxy So-L-norleucine, doxorubicin, morpholino-doxorubicin, cyanomorpholin Nodoxorubicin, 2-pyrrolinodoxorubicin and deoxydoxorubicin, epi Rubicin, eribulin, esorubicin, idarubicin, marcelomycin, maitomycin Nitomycins, mycophenolic acid, nogaramycin, olibomycins Peplomycin, Potphyllomycin, Puromycin, Queramycin, Rodolby Syn, streptonigrin, streptozosin, tuberculosis Antibiotics selected from cidin, ubenimex, dinostatin, and zolubicin; i) Polyketides (acetogenins), bula tasin and bula tasinone; gemcitabine, Epoxomicin derivatives and carfilzomib, bortezomib, thalidomide, lenalidomide, Pomalidomide, Tosedostat, Xyblestat, PLX4032, STA-909 0. Stimavax, Allovectin-7, Zygeba, Provenge, Elboy, isoprenylation inhibitors and lovastatin, dopaminergic neurotoxins and 1-methyl Tyl-4-phenylpyridine ion, cell cycle inhibitor (including staurosporine), A Cutinomycin derivatives (including actinomycin D and dactinomycin), amanitin derivatives, Bleomycin derivatives (including bleomycin A2, bleomycin B2, and peplomycin). ), anthracyclines (daunorubicin, doxorubicin (adriamycin), i Includes darbicin, epirubicin, pirarubicin, and zorubicin, mitoxantrone, MDR inhibitors or verapamil, Ca ２＋ ATP inhibitors or thapsigargin, histone deactivation Cetyltransferase inhibitors (vorinostat, romidepsin, panobinostat, valproic acid, Mosetinostat (MGCD0103), Bellinostat, PCI-24781, Enchi Nostat, SB939, Resminostat, Gibinostat, AR-42, CUDC- 101, containing sulforaphane and trichostatin A; thapsigargin, celecoxyl B, glitazones, epigallocatechin gallate, disulfiram, salinosporamide A, Anti-adrenal drugs (selected from the group consisting of aminoglutethimide, mitotane, and trilostanca) ;Aceglaton;Aldophosphamide cricoside;Aminolevulinic acid;Amsacrin (a msacrine; arabinoside, bestlovesil; bisantrene; edatrexate Defofamine; Demecolsin; Diazicon; Elfornithine (DFMO), Elf Omitin; eriptinium acetate; ethocluside, gallium nitrate, gasitosine, hydroxy Urea; ibandronate, lentinan; ronidamin; mitogazon; mopidamol; nitrate Laculin; Pentostatin; Fenamet; Pirarubicin; Podophyllic acid; 2-ethyl Hydrazide; Procarbazine; PSK (registered trademark); Lazoxane; Rhizoxin; Schizophy Lan; spirogermanium; tenuazonic acid; triadicone; 2,2',2''-tric Llorotriethylamine; Trichothecenes (T2 toxin, belcarin A, loridine A, and (Contains bianguidin); urethane, siRNA, antisense drugs; 2) Anti-autoimmune disease drugs: cyclosporine, cyclosporine A, aminocaproic acid, azalea Thioprine, bromocriptine, chlorambucil, chloroquine, cyclophosphamide, Luticoids (amcinonides, betamethasone, budesonide, hydrocortisone, flunico) Lido, fluticasone propionate, fluocortrondanazole (fluocortrondanazole) (Trolone danazol), dexamethasone, triamcinolone acetonide, di Contains beclomethasone propionate, DHEA, etanercept, hydroxychloro Kin, infliximab, meloxicam, methotrexate, mofetil, mycophenol Calcium acid, prednisone, sirolimus, tacrolimus; 3) Anti-infective drugs: a) Aminoglycosides: Amikacin, Astromycin, Gentamicin (Netyl Mycin, shisomycin, isepamycin), hygromycin B, kanamycin (Ami Casin, Arbekacin, Bekanamycin, Dibekacin, Tobramycin, Neomycin (Flamycin, Paromomycin, Ribostamycin), Netylmycin, Spectinoma Icin, streptomycin, tobramycin, verdamicin; b) Amphenicols: Azidamphenicol, Chloramphenicol, Florf Phenicol, thianphenicol; c) Ansamycins: geldanamycin, herbimycin; d) Carbapenems: biapenem, doripenem, ertapenem, imipenem, shiras Tachin, meropenem, panipenem; e) Cephalosporins: Carbasepom (loracalbef), cefacetril, cefaclor , cefradin, cephadroxyl, cephalonium, cephaloridine, cephalothin or Cephalothin, cephalexin, cephaloglysin, cephamandol, cefapillin, Cephatrizine, Cefazaflu, Cefazedone, Cefazolin, Cefbuperazone, Cefca Pen, cefdaroxime, cefepime, cefminox, cefoxitin, cefprodil, Cefuroxazine, ceftezol, cefuroxime, cefixime, cefdinir, cefditoren , cefepime, cefetamet, cefmenoxime, cefozidime, cefonisid, cefope Lazon, Cefolanide, Cefotaxime, Cefotiam, Cefozopran, Cephalexi Cefpimisole, cefpyramide, cefpirome, cefpodoxime, cefprodil, cef Quinom, Cefthulozine, Ceftazidime, Cefteram, Ceftibutene, Cefthiolen, Cef Tizoxim, ceftoviprol, ceftriaxone, cefuroxime, cefzonam, cefam Icin (including cefoxitin, cefotetan, and cefmetazole), oxacephalos ( (Fromoxef, Latamoxef); f) Glycopeptides: Bleomycin, Vancomycin (Oritavancin, Teravancin) Contains ), teicoplanin (darbavancin), lamopranin; g) Glycylcyclines: Tigecycline; h) β-lactamase inhibitors: Penam (sulbactam, tazobactam), Clavam ( Clavulanic acid; i) Lincosamides: clindamycin, lincomycin; j) Lipopeptides: Daptomycin, A54145, calcium-dependent antibiotics ( CDA); k) Macrolides: Azithromycin, cesromycin, clarithromycin, di Rithromycin, Erythromycin, Flurithromycin, Josamycin, Ketolide (Telithromycin, cesromycin), midecamycin, myocamycin, oleand Mycin, Rifamycin (Rifampicin, Rifampin, Rifabutin, Rifape (Lactin), rokitamycin, roxithromycin, spectinomycin, spiramycin tacrolimus (FK506), troleandomycin, telithromycin; l) Monobactams: aztreonam, tigemonam; m) Oxazolidinones: linezolids; n) Penicillins: Amoxicillin, ampicillin, pivanpicillin, hetacillin, Bacampicillin, Methampicillin, Tarampicillin, Azidocillin, Azurocillin, Ben Zilpenicillin, benzathine benzylpenicillin, benzathine phenoxymethylpenicillin N, clomethicillin, procaine benzylpenicillin, carbenicillin (kalindacillin) ), cloxacillin, dicloxacillin, epicillin, flucloxacillin, mesilinum (Pibmecillinum), mezlocillin, methicillin, nafcillin, oxacillin, penamecillin Phosphorus, penicillin, pheneticillin, phenoxymethylpenicillin, piperacillin, pro Picillin, Sulbenicillin, Temocillin, Ticarcillin; o) Polypeptides: bacitracin, colistin, polymyxin B; p) Quinolones: Alatrofloxacin, valofloxacin, ciprofloxacin, Clinafloxacin, danofloxacin, difloxacin, enoxacin, enrofloxacin Sacin, Floxin, Galenoxacin, Gatifloxacin, Gemifloxacin, Grepaf Roxacin, Canotorobafloxacin, Levofloxacin, Lomefloxacin, Marbof Roxacin, Moxifloxacin, Nadifloxacin, Norfloxacin, Orbifloxacin Sacin, ofloxacin, pefloxacin, trovafloxacin, grepafloxacin, Sitafloxacin, sparfloxacin, temafloxacin, tosufloxacin, trova Floxacin; q) Streptogramins: Pristinamycin, Quinupristine / Dalphopris Chin; r) Sulfonamides: Mafenide, prontosil, sulfacetamide, sulfame Tisol, sulfanilamide, sulfasalazine, sulfisoxazole, trimethop Limu, trimethoprim-sulfamethoxazole (co-trimoxazole); s) Steroidal antibacterial agents: Selected from fusidic acid; t) Tetracyclines: Doxycycline, Chlortetracycline, Chlortetracycline Clin, demeclocycline, rimecycline, meclocycline, metacycline, mi Nocycline, oxytetracycline, penimepicycline, lolitetracycline, Tetracyclines, glycylcyclines (including tigecyclines); u) Other antibiotics: annonasine, arsphenamine, bactoprenol inhibitors (Bacitracin), DADAL / AR inhibitor (cycloserine), dictyostatin, Discodermolide, eleuterobin, epothylone, ethambutol, etoposide, f Lopenem, Fusidic acid, Furazolidone, Isoniazid, Laurimalid, Metronidazole Mupirocin, mycolactone, NAM synthesis inhibitor (fosfomycin), nitrofurant In, paclitaxel, platensimycin, pyrazinamide, quinupristin / dalhop Listin, rifampicin (rifampin), tazobactamtinidazole, uvarcin; (4) Antiviral drugs: a) Invasion / fusion inhibitors: Apraviroc, Maraviroc, Vicriviroc, GP41 Enfvirtide), PRO140, CD4 (ibalizumab); b) Integrase inhibitors: raltegravir, elvitegravir, globoidnan A ； c) Maturation inhibitors: Bevirimat, Vivicon; d) Neuraminidase inhibitors: oseltamivir, zanamivir, peramivir; e) Nucleosides and nucleotides: abacavir, acyclovir, adefovir, a Mudoxovir, Applicitabine, Brivudine, Cidofovir, Klevudine, Dexerubushi Tabine, didanosine (DDI), erbucitabine, emtricitabine (FTC), enthe Kavir, famciclovir, fluorouracil (5-FU), 3'-fluorosubstituted 2', 3'-deoxynucleoside analog (3'-fluoro-2',3'-dideoxythymidine) (FLT) and 3'-fluoro-2',3'-dideoxyguanosine (FLG) (Includes the group:) Homivirsen, Ganciclovir, Idoxuridine, Lamivudine (3TC) , L-nucleoside (group consisting of β-L-thymidine and β-L-2'-deoxycytidine) Includes: penciclovir, rascivir, ribavirin, stampidine, stabidine set. (d4T), taribavirin (viramidine), terbivudine, tenofovir, trifluridine Mvalacyclovir, valganciclovir, zalcitabine (ddC), zidovudine (AZT) ）； f) Non-nucleosides: amantadine, ateviridine, capravirine, diarylpyri Midine (etravirine, rilpivirine), delavildin, docosanol, emibilin, e Favirenz, Foscarnet (phosphorylformate), Imiquimod, Interferon α, Robilide, rodenosine, methisazone, nevirapine, NOV-205, pegylated interferon α, podophyllotoxin, rifampicin, rimantadine, reciquimod (R-848) , tromantadine; g) Protease inhibitors: amprenavir, atazanavir, boceprevir, darunavir Lu, fosanprenavir, indinavir, lopinavir, nelfinavir, preconalil, Ritonavir, saquinavir, telaprevir (VX-950), tipranavir; h) Other types of antiviral drugs: Abzyme, Arbidol, Caranolid A, Celage Nin, cyanobilin-n, diarylpyrimidine, epigallocatechin gallate (EGCG) ), foscarnet, griffiscin, taribavirin (piramidine), hydroxycarb Mido, KP-1461, Miltefosine, Preconalil, Portmanto inhibitor, Ribavit Phosphate, sericiclib; (5) Salts, acids, derivatives, hydrates or hydrates of any of the above drugs that are pharmaceutically acceptable Salt; or crystalline structure; or optical isomer, racemic compound, diastereomer or enantiomeric compound Omar.

23. The synergistic agent described in claim 42 is selected from one or more of the following drugs: abatasep To, Abemaciclib, Abiraterone acetate, Abraxane, Acetaminophen / Hydroxyconate Don, acalabrutinib, aducanumab, adalimumab, ADXS31-142, AD XS-HER2, afatinib dimalate, aldesleukin, alectinib, Alem Tuzumab, alitretinoin, ad-tras tuzumab emtansine, amphetamine / de Xtroamphetamine, anastrozole, aripiprazole, anthracycline, Aripiprazole, atazanavir, atezolizumab, atorvastatin, avelumab, A xicabtageneciloleucel, axitinib, bellinostat, raw BC G, bevacizumab, bexarotene, blinatumomab, bortezomib, bosutinib, bren Tuximab vedotin, brigatinib, budesonide, budesonide / formoterol, bupre Norphin, cabazitaxel, cabozatinib, capmatinib, capecitabine, calfil Zomib, T (CAR-T) cells modified with chimeric antigen receptors, celecoxib, ceritini Bu, cetuximab, kidamide, cyclosporine, cinacalcet, crizotinib, cobimethoprim Tinib, Cosentyx, Crizotinib, Tisagenlecure, C TL019, dabigatran, dabrafenib, dacarbazine, daclizumab, dacomotinib Daptomycin, daratumumab, darbepoetin α, darunavir, dasatinib, den Roykindifutitox, denosumab, Depakote, Dexlansop Razole, Dexmethylphenidate, Dexamethasone, DigniCap Cooli ng System, dinutuximab, doxycycline, duloxetine, duberis B, durvalumab, elotuzumab, emtricibine / rilpivirine / tenofovir, fuma Disoproxil urate, emtricitabine / tenofovir / efavirenz, enoxaparin ensartinib, enzalutamide, epoetin α, erlotinib, esomeprazole, Eszopiclone, etanercept, everolimus, exemestane, everolimus, ex Senatide ER, Ezetimibe, Ezetimibe / Simvastatin, Fenofibrate, Phil Grastim, fingolimod, fluticasone propionate, fluticasone / salmeterol Lu, fulvestrant, Gazyva, gefitinib, glatiramer, guarella acetate Cerelin, Icotinib, Imatinib, Ibritumomab tiuxetan, Ibrutinib, Ide Larisib, Ifosfamide, Infliximab, Imiquimod, ImmuCyst, Im munoBCG, iniparib, insulin aspart, insulin detemir, insulin Glargine, insulin lispro, interferon α, interferon α-1b, Interferon α-2a, Interferon α-2b, Interferon β, Interf Interferon β1a, Interferon β1b, Interferon γ-1a, Lapatinib, Ip Limumab, Ipratropium bromide / Salbutamol, Ixazomib, Kanuma a) Lanreotide acetate, lenalidomide, lenariomide, lenvatinib mesylate, retro Zole, levothyroxine, levothyroxine, lidocaine, linezolid, liraglutide, li Sudexamfetamine, LN-144, lorlatinib, memantine, methylphenidate Metoprolol, Mekinist, Mericitabine / Rilpivirine / Tenofovir, Modafini Mometasone, Mycidac-C, Necitumumab, Neratinib, Nilotinib, Nirapa Rib, nivolumab, ofatumumab, obinutuzumab, olaparib, olmesartan, O Lumesartan / hydrochlorothiazide, omalizumab, omega-3 fatty acid ethyl ester, on Choline, oseltamivir, osimertinib, oxycodone, palbociclib, palivizma B, panitumumab, panobinostat, pazopanib, pembrolizumab, PD-1 antibody, PD-L1 antibody, pemetrexed, pertuzumab, pneumococcal conjugate vaccine, pomalidomide Pregabalin, ProscaVax, propranolol, quetiapine, rabeprazo Lu, radium-223 chloride, raloxifene, raltegravir, ramucirumab, raniviz Mab, regorafenib, ribociclib, rituximab, rivaroxaban, romidepsin, Rosuvastatin, ruxolitinib phosphate, salbutamol, savolitinib, semaglutide Sevelamer, sildenafil, siltuximab, ciplucel-T, sitagliptin sitagliptin / metformin, solifenacin, solanezumab, sonidegib, soraf Enib, sunitinib, tacrolimus, tacrimus, tadalafil, tamoxifen, taph Tafinlar, Talimogen Rachelpalebbek (laherparepvec), thalazoparib, telaprevir, thalazoparib, temozo Limid, Temsirolimus, Tenofovir / Emtricitabine, Disoproxil Fumarate Tenofo Hovir, testosterone gel, thalidomide, TICE BCG, tiotropium bromide, Tisagenlecleucel, toremifene, tramethicone Nib, trastuzumab, trabectedin (ecteinascidin 743), tra Metinib, tremelimumab, trifluridine / tipiracil, Uro-BCG, ustequin Mab, valsartan, veliparib, vandetanib, vemurafenib, venetoclax, Vorinostat, ziboo-aflibercept, and zostavax, and their analogues derivatives, pharmaceutically acceptable salts, carriers, diluents or excipients for these, or These combinations.