Your browser doesn't support javascript.
loading
Novel Series of Potent Glucokinase Activators Leading to the Discovery of AM-2394.
Dransfield, Paul J; Pattaropong, Vatee; Lai, Sujen; Fu, Zice; Kohn, Todd J; Du, Xiaohui; Cheng, Alan; Xiong, Yumei; Komorowski, Renee; Jin, Lixia; Conn, Marion; Tien, Eric; DeWolf, Walter E; Hinklin, Ronald J; Aicher, Thomas D; Kraser, Christopher F; Boyd, Steven A; Voegtli, Walter C; Condroski, Kevin R; Veniant-Ellison, Murielle; Medina, Julio C; Houze, Jonathan; Coward, Peter.
Afiliação
  • Dransfield PJ; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Pattaropong V; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Lai S; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Fu Z; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Kohn TJ; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Du X; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Cheng A; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Xiong Y; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Komorowski R; Departments of Metabolic Disorders, Comparative Biology and Safety Sciences and Pharmacokinetics and Drug Metabolism, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Jin L; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Conn M; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Tien E; Departments of Metabolic Disorders, Comparative Biology and Safety Sciences and Pharmacokinetics and Drug Metabolism, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • DeWolf WE; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Hinklin RJ; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Aicher TD; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Kraser CF; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Boyd SA; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Voegtli WC; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Condroski KR; Array BioPharma Inc. , 3200 Walnut Street, Boulder, Colorado 80301, United States.
  • Veniant-Ellison M; Departments of Metabolic Disorders, Comparative Biology and Safety Sciences and Pharmacokinetics and Drug Metabolism, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
  • Medina JC; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Houze J; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
  • Coward P; Departments of Therapeutic Discovery, Metabolic Disorders, and Pharmacokinetics and Drug Metabolism, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
ACS Med Chem Lett ; 7(7): 714-8, 2016 Jul 14.
Article em En | MEDLINE | ID: mdl-27437083
ABSTRACT
Glucokinase (GK) catalyzes the phosphorylation of glucose to glucose-6-phosphate. We present the structure-activity relationships leading to the discovery of AM-2394, a structurally distinct GKA. AM-2394 activates GK with an EC50 of 60 nM, increases the affinity of GK for glucose by approximately 10-fold, exhibits moderate clearance and good oral bioavailability in multiple animal models, and lowers glucose excursion following an oral glucose tolerance test in an ob/ob mouse model of diabetes.
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2016 Tipo de documento: Article