BMS-309403 | FABP4 inhibitor

BMS-309403 (300657-03-8) is a potent (Ki <2 nM FABP4, Ki = 250 nM FABP3, Ki = 350 nM FABP5) and selective inhibitor of the fatty-acid-binding protein aP2 (FABP4).^1,2 It demonstrated marked reductions in atherosclerotic lesions in an Apoe^-/- mouse model and improved glucose metabolism, reduced inflammation, and increased insulin sensitivity in a Lep^ob/obmouse model. BMS-309403 stimulated glucose uptake in myotubes via activation of AMPK.³ It decreased ER stress-associated inflammation in skeletal muscle⁴ and suppressed inflammation and oxidative stress in mouse and cell models of acute lung injury⁵.

References/Citations:

1) Furuhashi et al. (2007), Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2; Nature 447 959
2) Sulsky et al. (2007), Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP); Bioorg. Med. Chem. Lett., 17 3511
3) Lin et al. (2012), BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase; PLoS One, 7 e44570
4) Bosquet et al. (2018), FABP4 inhibitor BMS3409403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation; Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1863 604
5) Gongl et al. (2018), FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury; Biochem. Biophys. Res. Commun., 496 1115