PF-6260933

PF-6260933 is an inhibitor of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4; IC₅₀ = 3.7 nM).¹ It is selective for MAP4K4 over a panel of 41 kinases at 1 µM but also inhibits TRAF2- and NCK-interacting kinase (TNIK) and misshapen-like kinase 1 (MINK1; IC₅₀s = 15 and 8 nM, respectively). PF-6260933 inhibits the replication of CMV strains AD169 and Merlin(R1111) strains in human foreskin fibroblast (HFF) cells (EC₅₀s = 9.6 and 13.3 µM, respectively).² It inhibits collagen- or thrombin-induced aggregation of isolated human platelets by 70.9 and 61.2%, respectively, when used at a concentration of 20 µM.³ It decreases plaque formation in ApoE^-/- mice fed a Western diet in a model of atherosclerosis when administered at a dose of 10 mg/kg.⁴ PF-6260933 (15 mg/kg) decreases LPS-induced increases in TNF-α levels in wild-type mice and fasting blood glucose levels in ob/ob mice.¹

WARNING This product is not for human or veterinary use.

1. Ammirati, M., Bagley, S.W., Bhattacharya, S.K., et al. Discovery of an in vivo tool to establish proof-of-concept for MAP4K4-based antidiabetic treatment. ACS Med. Chem. Lett. 6(11), 1128-1133 (2015).

2. Strang, B.L., Asquith, C.R.M., Moshrif, H.F., et al. Identification of lead anti-human cytomegalovirus compounds targeting MAP4K4 via machine learning analysis of kinase inhibitor screening data. PLoS One 13(7), e0201321 (2018).

3. Nam, G.S., Kim, S., Kwon, Y.-S., et al. A new function for MAP4K4 inhibitors during platelet aggregation and platelet-mediated clot retraction. Biochem. Pharmacol. 188, 114519 (2021).

4. Roth Flach, R.J., Skoura, A., Matevossian, A., et al. Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis. Nat. Commun. 6, 8995 (2015).