BI-2545

BI-2545 represents a suitable chemical probe for ENPP2.  While of a similar chemical class to PF-8380, BI-2545 is more potent in whole blood experiments and achieved high in vivo potency when administered orally in rat.  Additionally, a structurally negative control is provided with BI-3017 to aid in experiments

In the original article, the compound is dissolved in 0.5% Natrosol For p.o. admistration. The compound can also be administered i.v. by dissolving in 7% HP-β-CD.

The benzotriazole BI-2545 compound is a potent inhibitor of human Autotaxin (ATX) both in cells (IC50 of 29 nM) and in vivo (IC50 of 96 nM in rodents).

ATX is an enzyme that controls levels of lysophosphatidic acid (LPA) by converting

lysophosphatidylcholine (LPC) into LPA. LPA is involved in cell signalling, mediating a wide range of biological effects in many tissue type, and it is associated to disease pathology characterised by abnormal cell migration. In vivo studies have shown that a single oral dose of BI-2545 at 10 mg/kg a LPA reduction of up to 90% in rats.

The crystal structure of ATX in complex with BI-2545 is available (PDB ID: 5OHI, 1.66 Å resolution). This compound belongs to the Type I inhibitors that occupy the orthosteric site, mimicking the LPC substrate mode of binding.

The compound has been developed for the potential treatment of idiopathic pulmonary fibrosis (IPF), but inhibition of ATX has also been investigated as promising target for treating chronic inflammatory diseases that underlie several other medical conditions, such as cancer, cardiovascular diseases, and rheumatoid arthritis.

This compound is a valuable chemical probe, and it has the advantage that there is another molecule from the same family of compounds that can be used as inactive control (compound BI-3017, also freely available).