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Identification of RO4597014, a Glucokinase Activator Studied in the Clinic for the Treatment of Type 2 Diabetes.
Qian, Yimin; Corbett, Wendy L; Berthel, Steven J; Choi, Duk Soon; Dvorozniak, Mark T; Geng, Wanping; Gillespie, Paul; Guertin, Kevin R; Haynes, Nancy-Ellen; Kester, Robert F; Mennona, Francis A; Moore, David; Racha, Jagdish; Radinov, Roumen; Sarabu, Ramakanth; Scott, Nathan R; Grimsby, Joseph; Mallalieu, Navita L.
Affiliation
  • Qian Y; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Corbett WL; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Berthel SJ; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Choi DS; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Dvorozniak MT; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Geng W; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Gillespie P; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Guertin KR; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Haynes NE; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Kester RF; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Mennona FA; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Moore D; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Racha J; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Radinov R; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Sarabu R; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Scott NR; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Grimsby J; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
  • Mallalieu NL; Departments of Discovery Chemistry, Pharmaceutical and Analytical Research, Metabolic and Vascular Diseases, Drug Metabolism and Pharmacokinetics, Process Research, Clinical Pharmacology, Hoffmann-La Roche , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
ACS Med Chem Lett ; 4(4): 414-8, 2013 Apr 11.
Article in En | MEDLINE | ID: mdl-24900686
ABSTRACT
To resolve the metabolite redox cycling associated with our earlier clinical compound 2, we carried out lead optimization of lead molecule 1. Compound 4 showed improved lipophilic ligand efficiency and demonstrated robust glucose lowering in diet-induced obese mice without a liability in predictive preclinical drug safety studies. Thus, it was selected as a clinical candidate and further studied in type 2 diabetic patients. Clinical data suggests no evidence of metabolite cycling, which is consistent with the preclinical profiling of metabolism.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies Language: En Journal: ACS Med Chem Lett Year: 2013 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies Language: En Journal: ACS Med Chem Lett Year: 2013 Type: Article Affiliation country: United States