Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.
The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.
Meng
Wei
W
Drug Safety Evaluation and Development, Bristol -Myers Squibb Company, Princeton, New Jersey 08543, USA. wei.meng@bms.com
Ellsworth
Bruce A
BA
Nirschl
Alexandra A
AA
McCann
Peggy J
PJ
Patel
Manorama
M
Girotra
Ravindar N
RN
Wu
Gang
G
Sher
Philip M
PM
Morrison
Eamonn P
EP
Biller
Scott A
SA
Zahler
Robert
R
Deshpande
Prashant P
PP
Pullockaran
Annie
A
Hagan
Deborah L
DL
Morgan
Nathan
N
Taylor
Joseph R
JR
Obermeier
Mary T
MT
Humphreys
William G
WG
Khanna
Ashish
A
Discenza
Lorell
L
Robertson
James G
JG
Wang
Aiying
A
Han
Songping
S
Wetterau
John R
JR
Janovitz
Evan B
EB
Flint
Oliver P
OP
Whaley
Jean M
JM
Washburn
William N
WN
D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013237:Stereoisomerism
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin