Eclitasertib

Eclitasertib is an inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK1, IC50 = 0.0375 µM). It inhibits necroptosis induced by TNF-alpha, a Smac mimetic, and Z-VAD-FMK in HT-29 cells (EC50 = 0.0154 µM, respectively). Eclitasertib (4 nM) inhibits necroptosis induced by IFN-gamma, TNF-alpha, Z-VAD, and an Smac mimetic and reduces cytokine levels induced by the same combination in primary human keratinocytes. It reduces epidermal thickness, reverses disruptions in epidermal architecture, and reduces IL-1 receptor A (IL-1RA) release in 3D keratinocyte skin equivalents generated from primary human keratinocytes and stimulated with mixed lesional T cell supernatants prepared from lichen planus (LP) and cutaneous lupus erythematosus (CLE) patient-derived skin biopsies. Eclitasertib (1 mg/kg) reverses TNF-alpha- and Z-VAD-induced hypothermia in a mouse model of systemic inflammatory response syndrome.. SMILES: O=C1N(C)C2=NC=CC=C2OC[C@@H]1NC(C(N3)=NN=C3CC4=CC=CC=C4)=O. InChi Code: InChI=1S/C19H18N6O3/c1-25-17-14(8-5-9-20-17)28-11-13(19(25)27)21-18(26)16-22-15(23-24-16)10-12-6-3-2-4-7-12/h2-9,13H,10-11H2,1H3,(H,21,26)(H,22,23,24)/t13-/m0/s1. InChi Key: XUZICJHIIJCKQQ-ZDUSSCGKSA-N