ML281

ML281 is a highly selective inhibitor of serine/threonine kinase 33 (STK33) with an IC₅₀ value of 14 nM. ML281 shows 700-fold selectivity over PKA and 550-fold over AurB. ML281 exerts core mechanism by inhibiting STK33: in small cell lung cancer, ML281 downregulates RPS6/BAD signaling phosphorylation, induces apoptosis, and suppresses proliferation, invasion^[1]. ML281 reduces STK33-mediated 4-hydroxyphenylpyruvate dioxygenase (HPD) phosphorylation in tyrosinemia ^[4]. ML281 is suitable for research on STK33 function, KRAS mutation-related cancers (pancreatic cancer, colon cancer, lung adenocarcinoma, etc.), small cell lung cancer, and tyrosinemia-related damage^[1][2][4] In Vitro:ML281 (10 μM; 72 hours) suppresses cell viability of NCI-H446 cells^[3].
ML281 exhibits potent inhibitory activity against purified recombinant serine/threonine kinase 33 (STK33) (IC₅₀ = 14 nM) ^[1].
ML281 (0.01-10 μM) has no significant effect on the viability of KRAS-dependent (NOMO-1, SKM-1) and KRAS-independent (THP-1, U937) acute myeloid leukemia-derived cell lines, ML281 does not exhibit selective cytotoxicity against KRAS-dependent cancer cells.^[1].
ML281 (10 μM; 72 h) suppresses RPS6/BAD signaling pathway in human small cell lung cancer NCI-H446 cells^[1].
ML281 (2.5-12.5 μM; 48 h) decreases T382 site phosphorylation of 4-hydroxyphenylpyruvate dioxygenase (HPD) and increases HPD protein expression in a dosage-dependent manner in human fetal hepatocyte LO2 cells^[4].
ML281 (10 μM; 48 h) abrogates enhanced HPD T382 phosphorylation and HPD degradation in Ttc36-deficient mouse primary hepatocytes^[4].