LX4211 & LX4212

Status
LX4211: Preclinical studies
LX4212: Preclinical studies

Indications
Diabetes

Overview
LX4211 and LX4212 are orally-delivered small molecules intended to manage type 2 diabetes by antagonizing sodium-glucose cotransporter type 2 (SGLT2). An SGLT2-inhibiting compound can potentially treat diabetes by increasing urinary glucose excretion, thereby lowering blood glucose levels.

Principal Targets
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 structural and 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; MAL, medullary ascending limb; CAL, cortical ascending limb; DCT, distal convoluted tubule; CCT, cortical convoluted tubule; OMCT, outer medullary convoluted tubule; IMCT, inner medullary convoluted tubule.

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