"目錄號: HY-13749B
Metabolic Enzyme/ProteaseAutophagy-
Sitagliptin(MK 0431)是DPP4高效抑制劑，在Caco-2細胞中IC50值為19nM。
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生物活性
Description
Sitagliptin phosphate monohydrate is a potent inhibitor ofDPP4withIC50of 19 nM in Caco-2 cell extracts
IC50& Target
IC50: 19 nM (DPP4, in Caco-2 cell extracts)
In Vitro
Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC50of 19 nM from Caco-2 cell extracts[1].?Sitagliptin reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involving cAMP/PKA/Rac1 activation[2].?A recent study demonstrates that sitagliptin exerts a novel, direct action in order to stimulate GLP-1 secretion by the intestinal L cell through a DPP-4-independent, protein kinase A- and MEK-ERK1/2-dependent pathway. It therefore reduces the effect of autoimmunity on graft survival[3].?
In Vivo
In vivo, the ED50value of sitagliptin phosphate for inhibition of plasma DPP-4 activity is calculated to be 2.3 mg/kg 7 hour postdose and 30 mg/kg 24 hour postdose in freely fed Han-Wistar rats[1].?The streptozotocin-induced type 1 diabetes mouse model exhibits elevated DPP-4 levels in the plasma that can be substantially inhibited in mice on an Sitagliptin phosphate diet. This is achieved by a positive effect on the regulation of hyperglycemia, potentially through prolongation of islet graft survival[4].?The plasma clearance and volume of distribution of Sitagliptin phosphate are higher in rats (40-48 mL/min/kg, 7-9 L/kg) than in dogs (9 mL/min/kg, 3 L/kg); and its half-life is shorter in rats,2 hours compared with 4 hours in dogs[5].?
Clinical Trial
Ono Pharmaceutical Co. Ltd
Type 2 Diabetes Mellitus
February 2009
Phase 3
Ono Pharmaceutical Co. Ltd-MSD K.K.
Type 2 Diabetes
Phase 3
Merck Sharp & Dohme Corp.
Type 2 Diabetes Mellitus
August 21, 2006
Phase 3
Merck Sharp & Dohme Corp.
Diabetes Mellitus, Type II
May 13, 2003
Phase 2
Merck Sharp & Dohme Corp.
Type 2 Diabetes Mellitus
March 17, 2005
Phase 3
Merck Sharp & Dohme Corp.
Diabetes Mellitus, Type 2
September 2004
Phase 3
Merck Sharp & Dohme Corp.
Type 2 Diabetes Mellitus
June 1, 2004
Phase 2
Merck Sharp & Dohme Corp.
Diabetes Mellitus, Type 2
June 2004
Phase 3
Merck Sharp & Dohme Corp.
Renal Insufficiency-Hemodialysis
January 2003
Phase 1
Merck Sharp & Dohme Corp.
Diabetes Mellitus, Type II
June 30, 2004
Phase 3
India Diabetes Research Foundation & Dr. A. Ramachandran's Diabetes Hospitals
Type 2 Diabetes
December 2011
Phase 3
Second Affiliated Hospital of Soochow University
Type 2 Diabetes
September 2016
University Health Network, Toronto-Merck Frosst Canada Ltd.
Hyperlipidemia
July 2012
Phase 2-Phase 3
European Foundation for the Study of Diabetes-Chinese Medical Association-Eli Lilly and Company
Type 1 Diabetes
January 2010
Phase 1-Phase 2
Kyunghee University Medical Center
Healthy
February 2015
Phase 3
Novartis Pharmaceuticals-Novartis
Diabetes Mellitus Type 2
November 2012
Phase 4
AstraZeneca
Type 2 Diabetes Mellitus
March 2010
Phase 1
Stanford University-Merck Sharp & Dohme Corp.
Heart Failure, Congestive
April 2008
Early Phase 1
IngridJazet-Merck Sharp & Dohme Corp.-Leiden University Medical Center
Neoplasms, Adipose Tissue
March 2014
Phase 4
University of Colorado Denver School of Medicine Barbara Davis Center
Type 1 Diabetes
September 2009
Phase 4
Kaleida Health-Merck Sharp & Dohme Corp.
Type 2 Diabetes
March 2008
Sherif S. Farag-National Heart, Lung, and Blood Institute (NHLBI)-Indiana University
Acute Myeloid Leukemia-Acute Lymphoid Leukemia-Hematopoetic Myelodysplasia-Leukemia, Myelogenous, Chronic-Lymphoma, Non-Hodgkin
November 2, 2012
Phase 2
Merck Sharp & Dohme Corp.
Type 2 Diabetes
March 1, 2010
Phase 3
Merck Sharp & Dohme Corp.
Type 2 Diabetes
July 18, 2008
Phase 1
Seoul National University Bundang Hospital
Diabetes
January 2009
Phase 4
Charles Drew University of Medicine and Science-National Center for Research Resources (NCRR)
Type 2 Diabetes Mellitus
January 2008
Phase 4
Laval University-Merck Sharp & Dohme Corp.
Type 2 Diabetes Mellitus
August 1, 2015
Phase 3
Laval University-Merck Sharp & Dohme Corp.
Type 2 Diabetes Mellitus
April 2011
Phase 3
Indiana University School of Medicine-Indiana University
Leukemia, Myeloid, Acute-Acute Lymphoblastic Leukemia-Myelodysplasia-Leukemia, Myelogenous, Chronic-Lymphoma, Non-Hodgkin
March 2009
Phase 2
Anna Cruceta-Fundacion Clinic per a la Recerca Biomédica
DIABETES Mellitus Type 2 Not Well Controlled
March 2013
Phase 4
Blandine Laferrere-Merck Sharp & Dohme Corp.-Columbia University
Type 2 Diabetes Mellitus
July 2012
Merck Sharp & Dohme Corp.
Diabetes Mellitus
March 1, 2008
Phase 4
University of Nebraska
Diabetes-Kidney Transplant
July 2009
Phase 4
University of Oklahoma
Kidney Transplant-Type 2 Diabetes
April 2007
University of Colorado, Denver-National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Healthy
November 2009
Phase 4
Seoul National University Bundang Hospital-Astellas Pharma Korea, Inc.
Type 2 Diabetes Mellitus
April 25, 2017
Phase 3
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran-Merck Sharp & Dohme Corp.
Reactive Hypoglycemia
December 2008
Phase 4
Merck Sharp & Dohme Corp.-Duke Clinical Research Institute, Oxford Diabetes Trials Unit
Type 2 Diabetes Mellitus
December 10, 2008
Phase 3
Kathleen Dungan-Ohio State University
Diabetes Mellitus, Type 2-Hyperglycemia
January 2014
Phase 4
Sung-Chen Liu-Mackay Memorial Hospital
Type 2 Diabetes
October 2009
Phase 4
Novartis Pharmaceuticals-Novartis
Diabetes Mellitus Type 2
June 2011
Phase 4
Merck Sharp & Dohme Corp.
Diabetes Mellitus Non-insulin-dependent
March 2008
Phase 1
Lawson Health Research Institute-The Physicians' Services Incorporated Foundation
Type 2 Diabetes-Nonalcoholic Steatohepatitis
December 2010
Georgetown University-Merck Sharp & Dohme Corp.
Type II Diabetes
January 2014
Phase 4
University of Oslo School of Pharmacy-Oslo University Hospital
Glucose Intolerance
September 2008
Phase 4
Merck Sharp & Dohme Corp.
