In vitro activity: ML348 (also known as CID 3238952; SID 160654487) is a reversible inhibitor of LYPLA1 (Lysophospholipase 1) with an IC50 value of 210 nM. It exhibits 14-fold selectivity for LYPLA1 over LYPLA2, ML348 is also selective over a panel of ~30 other serine hydrolases. Protein palmitoylation is an essential post-translational modification necessary for trafficking and localization of regulatory proteins that play key roles in cell growth and signaling. Multiple oncogenes, including HRAS and SRC, require palmitoylation for malignant transformation. LYPLA1 has been identified as a candidate protein palmitoyl thioesterase responsible for HRAS depalmitoylation in mammalian cells.

Kinase Assay: ML348 is a selective and reversible lysophospholipase 1 (LYPLA1) inhibitor with an IC50 of 210 nM, and barely inhibits LYPLA2

Cell Assay: siRNA mediated knockdown or their inhibition with highly specific inhibitors ML348 and ML349 does not down-regulate NRAS signaling or decrease cell viability. In contrast, palmostatin B showed a dose-dependent reduction of cell viability in a panel of NRAS mutant melanoma cell lines.