FABP4/5-IN-6

FABP4/5-IN-6 is an orally active, potent FABP4/5 inhibitor ( Ki = 0.41/2.53 μM), showing low selectivity over FABP3 ( Ki = 59.72 μM). FABP4/5-IN-6 inhibits the secretion of MCP-1 and IL-6 in Lipopolysaccharides (LPS)-induced THP-1 macrophage. FABP4/5-IN-6 exhibits significant anti-inflammatory effects and attenuates LPS-induced liver injury. FABP4/5-IN-6 has low hERG inhibition ( LD 50 > 2000 mg/kg). FABP4/5-IN-6 can be used for the study of Inflammation-related diseases ^[1].

In Vivo, FABP4/5-IN-6 (Compound Y18) (50 mg/kg, p.o., once daily for 4 days) exhibits significant anti-inflammatory and protective effects in mice. It effectively reduces LPS-induced liver damage, inhibits systemic and local hepatic inflammatory responses, and improves pathological damage to the liver and spleen^[1].

In Vitro, FABP4/5-IN-6 (Compound Y18) (80 μM, 24 h) shows no significant cytotoxicity to THP-1 cells, and cell viability is unaffected^[1]. FABP4/5-IN-6 (5-25 μM, 24 h) significantly inhibits LPS-induced secretion of MCP-1 and IL-6 in THP-1 macrophage cells, with the inhibitory effect showing a dose-dependent effect^[1].

References:
[1]. He Y, et al. Discovery of Potent and Selective FABP4/5 Inhibitors with an Isoquinolone Scaffold as Potential Therapeutics for Inflammation-Related Diseases. J Med Chem. 2025 Oct 9;68(19):20207-20227.