(R)-STU104

(R)-STU104 is a potent, first-in-class TAK1-MKK3 porotein-protein interaction (PPI) inhibitor with SPR Kd of 71 nM for binding MKK3, disrupting the TAK1 phosphorylating MKK3.(R)-STU104 exhibited the potent inhibitory activity on TNF-α production on RAW264.7 cells with IC50 of 0.58 uM, suppressed the TAK1/MKK3/p38/MnK1/MK2/elF4E signal pathways.(R)-STU104 demonstrated remarkable dose-effect relationships on both acute and chronic mouse ulcerative colitis (UC) models.(R)-STU104 showed better anti-UC efficacy in vivo at 10 mg/kg/d than mesalazine at the dose of 50 mg/kg/d.

1. Mei-Lin Tang, et al. J Med Chem. 2022 Apr 20. doi: 10.1021/acs.jmedchem.1c02198.