AR088328A1 - Agentes inductores de la apoptosis que pueden usarse para tratar el cancer y las enfermedades inmunes y autoinmunes - Google Patents
Agentes inductores de la apoptosis que pueden usarse para tratar el cancer y las enfermedades inmunes y autoinmunesInfo
- Publication number
- AR088328A1 AR088328A1 ARP120103812A ARP120103812A AR088328A1 AR 088328 A1 AR088328 A1 AR 088328A1 AR P120103812 A ARP120103812 A AR P120103812A AR P120103812 A ARP120103812 A AR P120103812A AR 088328 A1 AR088328 A1 AR 088328A1
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- nhc
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- independently selected
- nr8c
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Transplantation (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Compuestos que inhiben la actividad de las proteínas antiapoptóticas Bcl-xL, composiciones que contienen dichos compuestos y métodos para tratar enfermedades en las que se expresan las proteínas antiapoptóticas Bcl-xL. Reivindicación 1: Un compuesto caracterizado porque es de la fórmula (1) o una sal aceptable para terapia del mismo, o una sal aceptable para terapia del mismo, donde X es heteroarilo; donde el heteroarilo representado por X está opcionalmente sustituido con uno, dos, tres, o cuatro R⁴; Y¹ es fenileno, o heteroarileno C₅₋₆; opcionalmente fusionado con uno o dos anillos seleccionados entre el grupo que consiste en cicloalcano C₃₋₈, cicloalqueno C₃₋₈, benceno, heteroareno C₅₋₆, heterocicloalcano C₃₋₈, y heterocicloalqueno C₃₋₈; donde Y¹ está opcionalmente sustituido con uno, dos, tres, o cuatro sustituyentes seleccionados en forma independiente entre el grupo que consiste en R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; L¹ se selecciona entre el grupo que consiste en (CR⁶R⁷)q, (CR⁶R⁷)ₛ-O-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-C(O)-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-S-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-S(O)₂-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-NR⁶AC(O)-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-C(O)NR⁶A-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-NR⁶A-(CR⁶R⁷)ʳ, (CR⁶R⁷)ₛ-S(O)₂NR⁶A-(CR⁶R⁷)ʳ, y (CR⁶R⁷)ₛ-NR⁶AS(O)₂-(CR⁶R⁷)ʳ; e Y² se selecciona entre el grupo que consiste en alquilo C₃₋₁₁, de cadena ramificada, cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, fenilo, y heterociclilo C₃₋₇; donde cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, fenilo, y heterociclilo C₃₋₇ están opcionalmente fusionados con uno o dos anillos seleccionados entre el grupo que consiste en cicloalcano C₃₋₈, cicloalqueno C₃₋₈, benceno, heteroareno C₅₋₆, heterocicloalcano C₃₋₈, y heterocicloalqueno C₃₋₈; donde Y² está opcionalmente sustituido con uno, dos, tres, cuatro, o cinco sustituyentes seleccionados en forma independiente entre el grupo que consiste en R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, C(O)R⁸, CO(O)R⁸, OC(O)R⁸, OC(O)OR⁸, NH₂, NHR⁸, N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHS(O)₂R⁸, NR⁸S(O)₂R⁸, NHC(O)OR⁸, NR⁸C(O)OR⁸, NHC(O)NH₂, NHC(O)NHR⁸, NHC(O)N(R⁸)₂, NR⁸C(O)NHR⁸, NR⁸C(O)N(R⁸)₂, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, C(O)NHOH, C(O)NHOR⁸, C(O)NHSO₂R⁸, C(O)NR⁸SO₂R⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; o L¹ es un enlace; e Y² se selecciona entre el grupo que consiste en cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, fenilo, y heterociclilo C₃₋₇; donde cicloalquilo C₃₋₇, cicloalquenilo C₄₋₇, fenilo, y heterociclilo C₃₋₇ representado por Y² están opcionalmente fusionados con uno o dos anillos seleccionados entre el grupo que consiste en cicloalcano C₃₋₈, cicloalqueno C₃₋₈, benceno, heteroareno C₅₋₆, heterocicloalcano C₃₋₈, y heterocicloalqueno C₃₋₈; donde cada Y² y cada anillo fusionado con Y² están opcionalmente sustituidos con uno, dos, tres, cuatro, o cinco sustituyentes seleccionados en forma independiente entre el grupo que consiste en R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, C(O)R⁸, CO(O)R⁸, OC(O)R⁸, OC(O)OR⁸, NH₂, NHR⁸, N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHS(O)₂R⁸, NR⁸S(O)₂R⁸, NHC(O)OR⁸, NR⁸C(O)OR⁸, NHC(O)NH₂, NHC(O)NHR⁸, NHC(O)N(R⁸)₂, NR⁸C(O)NHR⁸, NR⁸C(O)N(R⁸)₂, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, C(O)NHOH, C(O)NHOR⁸, C(O)NHSO₂R⁸, C(O)NR⁸SO₂R⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; Z¹ se selecciona entre el grupo que consiste en C(O)OR⁹, C(O)NR¹⁰R¹¹, C(O)R¹¹, NR¹⁰C(O)R¹¹, NR¹⁰C(O)NR¹⁰R¹¹, OC(O)NR¹⁰R¹¹, NR¹⁰C(O)OR⁹, C(=NOR¹⁰)NR¹⁰R¹¹, NR¹⁰C(=NCN)NR¹⁰R¹¹, NR¹⁰S(O)₂NR¹⁰R¹¹, S(O)₂R⁹, S(O)₂NR¹⁰R¹¹, N(R¹⁰)S(O)₂R¹¹, NR¹⁰C(=NR¹¹)NR¹⁰R¹¹, C(=S)NR¹⁰R¹¹, C(=NR¹⁰)NR¹⁰R¹¹, halógeno, NO₂, y CN; o Z¹ se selecciona entre el grupo que consiste en el grupo de formulas (2); R¹, en cada instancia, se selecciona en forma independiente entre el grupo que consiste en halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; R², en cada instancia, se selecciona en forma independiente entre el grupo que consiste en deuterio, halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; dos R² que se unen al mismo átomo de carbono, junto con dicho átomo de carbono, forman opcionalmente un anillo seleccionado entre el grupo que consiste en heterocicloalquilo, heterocicloalquenilo, cicloalquilo, y cicloalquenilo; R³, en cada instancia, se selecciona en forma independiente entre el grupo que consiste en halo, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; R⁴, en cada instancia, se selecciona en forma independiente entre el grupo que consiste en NR¹²R¹³, OR¹², CN, NO₂, halógeno, C(O)OR¹², C(O)NR¹²R¹³, NR¹²C(O)R¹³, NR¹²S(O)₂R¹⁴, NR¹²S(O)R¹⁴, S(O)₂R¹⁴, S(O)R¹⁴ y R¹⁴; R⁵, en cada instancia, se selecciona en forma independiente entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, hidroxialquilo C₁₋₆, arilo, heterociclilo, cicloalquilo, y cicloalquenilo; R⁶A se selecciona en forma independiente entre el grupo que consiste en hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆; R⁶ y R⁷, en cada instancia, se seleccionan en forma independiente entre sí entre el grupo que consiste en hidrógeno, R¹⁵, OR¹⁵, SR¹⁵, S(O)R¹⁵, SO₂R¹⁵, C(O)R¹⁵, CO(O)R¹⁵, OC(O)R¹⁵, OC(O)OR¹⁵, NH₂, NHR¹⁵, N(R¹⁵)₂, NHC(O)R¹⁵, NR¹⁵C(O)R¹⁵, NHS(O)₂R¹⁵, NR¹⁵S(O)₂R¹⁵, NHC(O)OR¹⁵, NR¹⁵C(O)OR¹⁵, NHC(O)NH₂, NHC(O)NHR¹⁵, NHC(O)N(R¹⁵)₂, NR¹⁵C(O)NHR¹⁵, NR¹⁵C(O)N(R¹⁵)₂, C(O)NH₂, C(O)NHR¹⁵, C(O)N(R¹⁵)₂, C(O)NHOH, C(O)NHOR¹⁵, C(O)NHSO₂R¹⁵, C(O)NR¹⁵SO₂R¹⁵, SO₂NH₂, SO₂NHR¹⁵, SO₂N(R¹⁵)₂, CO(O)H, C(O)H, OH, CN, N₃, NO₂, F, Cl, Br y I; o R⁸, en cada instancia, se selecciona en forma independiente entre el grupo que consiste en alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, haloalquilo C₁₋₆, arilo, heterociclilo, cicloalquilo, y cicloalquenilo; donde R⁸ alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, y haloalquilo C₁₋₆ están opcionalmente sustituidos con uno, dos, tres, cuatro, cinco, o seis sustituyentes seleccionados en forma independiente entre el grupo que consiste en R¹⁶, OR¹⁶, SR¹⁶, S(O)R¹⁶, SO₂R¹⁶, C(O)R¹⁶, CO(O)R¹⁶, OC(O)R¹⁶, OC(O)OR¹⁶, NH₂, NHR¹⁶, N(R¹⁶)₂, NHC(O)R¹⁶, NR¹⁶C(O)R¹⁶, NHS(O)₂R¹⁶, NR¹⁶S(O)₂R¹⁶, NHC(O)OR¹⁶, NR¹⁶C(O)OR¹⁶,
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547165P | 2011-10-14 | 2011-10-14 | |
| CN2012078372 | 2012-07-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR088328A1 true AR088328A1 (es) | 2014-05-28 |
Family
ID=47073545
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP120103812A AR088328A1 (es) | 2011-10-14 | 2012-10-12 | Agentes inductores de la apoptosis que pueden usarse para tratar el cancer y las enfermedades inmunes y autoinmunes |
Country Status (23)
| Country | Link |
|---|---|
| EP (2) | EP2768830B1 (es) |
| JP (2) | JP6049738B2 (es) |
| KR (1) | KR102056587B1 (es) |
| CN (1) | CN109535155B (es) |
| AR (1) | AR088328A1 (es) |
| AU (2) | AU2012322818A1 (es) |
| BR (1) | BR112014009052B1 (es) |
| CA (1) | CA2850976C (es) |
| CL (1) | CL2014000922A1 (es) |
| CO (1) | CO6950477A2 (es) |
| DO (1) | DOP2014000074A (es) |
| EC (1) | ECSP14000606A (es) |
| ES (1) | ES2699966T3 (es) |
| IL (1) | IL231926A (es) |
| MX (2) | MX351970B (es) |
| PE (2) | PE20141997A1 (es) |
| PH (1) | PH12014500815B1 (es) |
| RU (1) | RU2594282C2 (es) |
| SG (2) | SG10201606031XA (es) |
| TW (1) | TWI561521B (es) |
| UY (1) | UY34381A (es) |
| WO (1) | WO2013055895A1 (es) |
| ZA (1) | ZA201402555B (es) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8889675B2 (en) | 2011-10-14 | 2014-11-18 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| TWI571466B (zh) * | 2011-10-14 | 2017-02-21 | 艾伯維有限公司 | 用於治療癌症及免疫與自體免疫疾病之細胞凋亡誘發劑 |
| WO2016094517A1 (en) * | 2014-12-09 | 2016-06-16 | Abbvie Inc. | Bcl-xl inhibitory compounds and antibody drug conjugates including the same |
| WO2016131100A1 (en) * | 2015-02-18 | 2016-08-25 | The Walter And Eliza Hall Institute Of Medical Research | Methods of treating infectious diseases |
| US10195213B2 (en) | 2015-03-13 | 2019-02-05 | Unity Biotechnology, Inc. | Chemical entities that kill senescent cells for use in treating age-related disease |
| WO2017107089A1 (en) | 2015-12-23 | 2017-06-29 | Merck Sharp & Dohme Corp. | 3- (1h-pyrazol-4-yl) pyridineallosteric modulators of the m4 muscarinic acetylcholine receptor |
| WO2019000236A1 (en) | 2017-06-27 | 2019-01-03 | Merck Sharp & Dohme Corp. | ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR |
| WO2019000238A1 (en) | 2017-06-27 | 2019-01-03 | Merck Sharp & Dohme Corp. | 5- (PYRIDIN-3-YL) OXAZOLE ALLOSTERIC MODULATORS OF M4 ACETYLCHOLINE MUSCARINIC RECEPTOR |
| WO2020210831A1 (en) * | 2019-04-12 | 2020-10-15 | TONIX Pharmaceuticals Holding Corp | Inhibitors of cd40-cd154 binding |
| KR102316961B1 (ko) * | 2020-01-29 | 2021-10-26 | 프라비바이오 주식회사 | 면역억제제로서의 벤젠 유도체의 면역억제용 약학적 조성물 |
| IL303048A (en) | 2020-11-24 | 2023-07-01 | Novartis Ag | Bcl-xl inhibitor antibody-drug conjugates and methods of use thereof |
| EP4288434A1 (en) | 2021-02-02 | 2023-12-13 | Les Laboratoires Servier | Selective bcl-xl protac compounds and methods of use |
| JP2025517435A (ja) | 2022-05-20 | 2025-06-05 | ノバルティス アーゲー | 抗新生物薬化合物の抗体－薬物コンジュゲートおよびその使用の方法 |
| CA3256012A1 (en) | 2022-05-20 | 2023-11-23 | Les Laboratoires Servier | ANTIBODY-DRUG CONJUGATES, MET INHIBITORS BCL-XL, AND THEIR METHODS OF USE |
| KR20250027281A (ko) | 2022-05-20 | 2025-02-25 | 노파르티스 아게 | Epha2 bcl-xl 억제제 항체-약물 접합체 및 그의 사용 방법 |
| TW202540185A (zh) | 2023-11-22 | 2025-10-16 | 法商施維雅藥廠 | 抗cd74抗體藥物結合物及其使用方法 |
| TW202540186A (zh) | 2023-11-22 | 2025-10-16 | 瑞士商諾華公司 | 抗ｃｄ７抗體藥物結合物及其使用方法 |
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