Chemical Name: Sotagliflozin
CAS No.:1018899-04-1
English name:LX-4211
Synonyms: Sotagliflozin;beta-L-Xylopyranoside,methyl5-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-thio-,(5S)-;(5S)-Methyl5-C-[4- chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-thio-beta-L-xylopyranosideSotagliflozinLP802034;LX421;CS-1853;LX-4211;SOTA-009;LP802034 EOS-61381;LX4211/LX-4211
Molecular Formula:C21H25ClO5S Molecular Weight:424.94
MOL File: 1018899-04-1.mol
Soglitazone Chemical Properties Boiling Point:607.9±55.0°C(Predicted)
Density:1.37±0.1g/cm3(Predicted)
Storage condition:Storeat-20°C
Solubility:DMSO:84.0(MaxConc.mg/mLChemicalbook);197.67(MaxConc.mM)Ethanol:17.0(MaxConc.mg/mL);40.01(MaxConc.mM)
Morphology:Powder
Acidity coefficient(pKa):12.87±0.70(Predicted)
Soglitazone Properties, Applications and Production Process
Overview
Soglitazone LX-4211 is a dual SGLT1/SGLT2 inhibitor with a novel hypoglycemic mechanism that has been shown to be effective in both type 1 and type 2 diabetes mellitus. In three pivotal multicenter phase III clinical studies of sogfilgrastim as an insulin adjuvant therapy for the treatment of type 1 diabetes, the sogfilgrastim group met the trial endpoints without severe hypoglycemia or other SAEs during the study period, which provides a clinical basis for the approval of sogfilgrastim as an insulin adjuvant therapy for the treatment of type 1 diabetes.
Applications
Soglitazone LX-4211 is a new oral diabetes drug co-developed by Sanofi and Lescol Pharmaceuticals. It acts as a dual inhibitor of SGLT-1 and SGLT-2 and is able to lower postprandial glucose, elevate GLP-1 and promote urinary glucose excretion.
Mechanism of action
SGLT has two main types, SGLT1 and SGLT2. SGLT1 is mainly expressed in the brush border of the small intestine and the S3 segment of the renal proximal tubule, with a small amount of epi-Chemicalbook reaching the heart, trachea and brain, and is mainly responsible for transporting glucose and galactose in the intestinal lumen and reabsorbing glucose in the renal proximal tubule that is not reabsorbed by SGLT2. SGLT2 is specifically expressed in the S1 segment of the renal proximal tubule and is responsible for the reabsorption of glucose from primary urine in the renal proximal tubule, mediating approximately 90% of renal glucose reabsorption. The mechanism of action of the marketed SGLT2 inhibitors is to reduce proximal tubular glucose reabsorption and increase urinary glucose excretion by selectively inhibiting SGLT2, thereby reducing blood glucose levels. Sogliflozin LX-4211, as a dual SGLT1/SGLT2 inhibitor, can inhibit SGLT2 and increase glucose excretion as well as SGLT1 and reduce glucose entry into blood via the gastrointestinal tract, thus effectively lowering blood glucose.
Biological activity
Sotagliflozin (LX4211,LP-802034) is an oral dual SGLT1/SGLT2 inhibitor with IC50 of 36 nM and 1.8 nM, respectively.Phase3.
Target Points
Target Value
SGLT2 1.8 nM
SGLT1 36 nM
In vitro studies
LX4211 inhibited [14C]AMG uptake with IC50s of 62.0 nM and 0.6 nM for SGLT1 and SGLT2 in mice, respectively.
In vivo studies
In mice, LX4211 (60 mg/kg, p.o. Chemicalbook) reduced intestinal glucose uptake by inhibiting SGLT1, resulting in a net increase in GLP-1 and PYY release and a decrease in GIP release and glucose fluctuations. In mice with type I diabetes and non-obese diabetic susceptibility, Sotagliflozin (30 mg/kg) significantly improved glycemic control without increasing the rate of hypoglycemia measurements.
