A-205804

A-205804 is an orally bioavailable, potent and selective lead inhibitor of E-selectin and ICAM-1 expression, with an IC50 of 20 nM and 25 nM for E-selectin and ICAM-1, respectively. A-205804 can be used in the research of chronic inflammatory diseases[1].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Cytoskeleton >> Integrin

IC50: 20 nM (E-selectin), 25 nM (ICAM-1)[1]

A-205804 exhibits Cellular Toxicities for HUVEC with an IC50 of 152 μM[1]. A-205804 is an effective inhibitor of cell-cell adhesion in an in vitro flow experiment, demonstrating relevance in a model physiological system[1].

A-205804 (5 mg/kg; p.o.) shows a half-life of 1 hour for rat[1]. A-205804 (10 mg/kg; p.o.; 3 times per week; for 2 weeks) attenuates the E-selectin expression on the endothelial vascular niche cells in mice[2]. Animal Model: C57BL/6 mice[2] Dosage: 10 mg/kg Administration: Oral administration, 3 times per week, for 2 weeks Result: Efficiently decreased the expression of E-selectin on the endothelial vascular niche cells Animal Model: Rat[1] Dosage: 5 mg/kg (Pharmacokinetic Analysis) Administration: Oral administration Result: t1/2 = 1 hour

[1]. Stewart AO, et al. Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression. J Med Chem. 2001 Mar 15;44(6):988-1002.

[2]. Morita K, et al. RUNX transcription factors potentially control E-selectin expression in the bone marrow vascular niche in mice. Blood Adv. 2018 Mar 13;2(5):509-515.