MF438

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 (Item Nos. 90260 | 24659).³ MF438 (1 µM) 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 µM. It acts synergistically with cisplatin (Item No. 13119) to induce apoptosis and autophagy in patient-derived NSCLC cells.⁴

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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 inhibitors. Bioorg. 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 cells. Cell 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 cells. Cancer Lett. 406, 93-104 (2017).