Your browser doesn't support javascript.
loading
Discovery of 4-((3'R,4'S,5'R)-6″-Chloro-4'-(3-chloro-2-fluorophenyl)-1'-ethyl-2″-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3″-indoline]-5'-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development.
Aguilar, Angelo; Lu, Jianfeng; Liu, Liu; Du, Ding; Bernard, Denzil; McEachern, Donna; Przybranowski, Sally; Li, Xiaoqin; Luo, Ruijuan; Wen, Bo; Sun, Duxin; Wang, Hengbang; Wen, Jianfeng; Wang, Guangfeng; Zhai, Yifan; Guo, Ming; Yang, Dajun; Wang, Shaomeng.
Afiliación
  • Aguilar A; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • Lu J; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • Liu L; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • Du D; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • Bernard D; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • McEachern D; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • Przybranowski S; University of Michigan Comprehensive Cancer Center, and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, University of Michigan , 1600 Huron Parkway, Ann Arbor, Michigan 48109, United States.
  • Li X; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
  • Luo R; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
  • Wen B; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
  • Sun D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
  • Wang H; Jiangsu Ascentage Biomed Development Inc. , China Medical City, Taizhou, Jiangsu 225300, China.
  • Wen J; Suzhou Ascentage Pharma Inc. , Suzhou, Jiangsu 215123, China.
  • Wang G; Jiangsu Ascentage Biomed Development Inc. , China Medical City, Taizhou, Jiangsu 225300, China.
  • Zhai Y; Suzhou Ascentage Pharma Inc. , Suzhou, Jiangsu 215123, China.
  • Guo M; Jiangsu Ascentage Biomed Development Inc. , China Medical City, Taizhou, Jiangsu 225300, China.
  • Yang D; Suzhou Ascentage Pharma Inc. , Suzhou, Jiangsu 215123, China.
  • Wang S; Jiangsu Ascentage Biomed Development Inc. , China Medical City, Taizhou, Jiangsu 225300, China.
J Med Chem ; 60(7): 2819-2839, 2017 04 13.
Article en En | MEDLINE | ID: mdl-28339198
We previously reported the design of spirooxindoles with two identical substituents at the carbon-2 of the pyrrolidine core as potent MDM2 inhibitors. In this paper we describe an extensive structure-activity relationship study of this class of MDM2 inhibitors, which led to the discovery of 60 (AA-115/APG-115). Compound 60 has a very high affinity to MDM2 (Ki < 1 nM), potent cellular activity, and an excellent oral pharmacokinetic profile. Compound 60 is capable of achieving complete and long-lasting tumor regression in vivo and is currently in phase I clinical trials for cancer treatment.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Pirrolidinas / Proteínas Proto-Oncogénicas c-mdm2 / Descubrimiento de Drogas / Neoplasias / Antineoplásicos Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Pirrolidinas / Proteínas Proto-Oncogénicas c-mdm2 / Descubrimiento de Drogas / Neoplasias / Antineoplásicos Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos