COMMENT 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 Jun 28 2020 - 8:56am; 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. Jun 28 2020 - 8:58am; 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). Jun 28 2020 - 9:00am

MOA Inhibitor (Chemical Probes.org)

DESCRIPTION BI-2545 inhibits human ATX with an IC50 of 2.2 nM. In human whole blood BI-2545 inhibits Autotaxin with an IC50 of 29 nM and in rat whole blood with an IC50 of 96 nM.6 In vivo BI-2545 demonstrated after a single oral dose to rats at 10 mg/kg a LPA reduction of up to 90%. We also offer BI-3017 as inactive control. (opnMe Portal)