MF438 is an inhibitor of stearoyl-CoA desaturase 1 (SCD1; IC50 = 2.3 nM for the rat enzyme), an enzyme that catalyzes the formation of a cis double bond at the ?9 position of stearoyl-CoA to produce oleoyl-CoA.1,2 It reduces spheroid formation in NCI H460 and patient-derived non-small cell lung cancer (NSCLC) cells in a concentration-dependent manner, an effect that can be blocked by oleic acid .3 MF438 (1 ?M) decreases the activity of aldehyde dehydrogenase 1A1 (ALDH1A1), a marker of cancer stem cells (CSCs), in NCI H460-derived spheroids when used at a concentration of 1 ?M. It acts synergistically with cisplatin to induce apoptosis and autophagy in patient-derived NSCLC cells.4
1.Léger, S., Black, C., Deschenes, D., et al.Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438)Bioorg. Med. Chem. Lett.20(2)499-502(2010) 2.Isabel, E., Powell, D.A., Black, W.C., et al.Biological activity and preclinical efficacy of azetidinyl pyridazines as potent systemically-distributed stearoyl-CoA desaturase inhibitorsBioorg. Med. Chem. Lett.21(1)479-483(2011) 3.Noto, A., Raffa, S., De Vitis, C., et al.Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cellsCell Death Dis.4(12)e947(2013) 4.Pisanu, M.E., Noto, A., De Vitis, C., et al.Blockade of stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cellsCancer Lett.40693-104(2017)