ML329

Description: ML329 is a potent small molecule inhibitor of MITF (Micropthalmia-associated transcription factor) which inhibits TRPM-1 (melastatin, a MITF target gene) promoter activity with an IC50 of 1.2 uM. MITF is a lineage restricted basic helix-loop-helix leucine zipper transcription factor that is essential for melanocyte development, function and survival. 15% of human melanomas have MITF gene amplification. In addition, a vast majority of melanomas are dependent upon MITF for survival. ML329 was discovered by a high throughput screening (HTS) of 331, 578 compounds from the NIH MLPCN compound library. ML329 was tested in two MITF-dependent melanoma cell viability assays, SK-MEL-5 and MALME-3M plus a MITF-independent cell line, A375. ML329 showed specific activity against the MITF-dependent cells, primary melanocytes but no effect on the viability in A375 cells. ML329 reduced the expression of multiple MITF target genes, including pigment-related genes and the cell cycle regulator CDK2. As a tool compound, ML329 will be useful in elucidating the role of MITF in melanocyte lineage development and in melanoma disease progression.

References: National Center for Biotechnology Information (US); 2010-2012 Dec.