Indications
Diabetes

Stage of Development
LX4211:  IND-enabling activities
LX4212:  Preclinical studies



Overview
LX4211 and LX4212 are orally-delivered small molecules under development as potential treatments for type 2 diabetes which work by inhibiting the sodium-glucose cotransporter type 2 (SGLT2).  SGLT2-inhibiting compounds can potentially treat diabetes by increasing urinary glucose excretion, thereby lowering blood glucose levels.

Key Target
The primary target of LX4211 and LX4212 is SGLT2, a transporter responsible for most of the glucose reabsorption performed by the kidney.  Lexicon scientists found that mice lacking SGLT2 have improved glucose tolerance and increased urinary glucose excretion.

This figure depicts a nephron, the basic functional unit of the kidney. The glucose reabsorption transporter, SGLT2, is expressed in the first segment of the proximal convoluted tubule (PCT S1) and is responsible for most of the glucose reabsorption that happens in the kidney. Abbreviations: PCT S1 and S2, proximal convoluted tubule segments 1 and 2; PST S3, proximal straight tubule segment 3.

Preclinical Data
In preclinical studies, animals treated with LX4211 and LX4212 demonstrated increased urinary glucose excretion and decreased blood HbA1c levels (a marker of long-term blood sugar levels).  Importantly, urinary glucose excretion returned to baseline after treatment was discontinued.