MRT67307

MRT67307 is a potent, dual inhibitor of IKKε and TBK-1 with IC50 of 160 and 19 nM at 0.1 mM ATP in vitro, also potently inhibit ULK1 and ULK2 in vitro (IC50=45 and 38 nM) and block autophagy in cells; the autophagy-inhibiting capacity of MRT67307 is specifically through ULK1, results in accumulation of stalled early autophagosomal structures in treated cells; increases IL-10 production and suppresses proinflammatory cytokine production in macrophages, increases CREB-dependent gene transcription by promoting the dephosphorylation of CRTC3; also inhibits MARK, NUAK and SIK isoforms in vitro with comparable potency to the IKK-related kinases.