Description
WHI-P131 is an inhibitor of JAK3 and EGFR that exhibits anticancer chemotherapeutic, chemopreventive, anti-inflammatory, and anti-diabetic properties. WHI-P131 is prophylactic against carcinogenesis induced by UVB exposure in vivo, delaying lesion appearance and decreasing lesion volume and number. WHI-P131 decreases plasma creatine kinase and lactate dehydrogenase activity, decreasing infarct size, myocardial apoptosis and deterioration, and inflammation in animal models of ischemia. Additionally, WHI-P131 decreases TNF-α-induced expression of ICAM-1, VCAM-1, and fractalkine, improving myocardial permeability in cellular models. WHI-P131 displays potential as a prophylactic treatment for diabetes, as its inhibition of JAK3 and suppression of NF-κB results in decreased production of NO and iNOS, preventing destruction of pancreatic islet cells.
References
Oh YB, Ahn M, Lee SM, et al. Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice. Exp Mol Med. 2013 May 17;45:e23. PMID: 23680658.
Lee JE, Lee AS, Kim DH, et al. Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor-α-induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice. Int J Mol Med. 2012 May;29(5):864-70. PMID: 22344597
Uckun FM, Dibirdik I, Qazi S. Prevention of UVB-induced skin inflammation, genotoxicity, and photocarcinogenesis in mice by WHI-P131, a dual-function inhibitor of Janus kinase 3 and EGF receptor kinase. Arzneimittelforschung. 2010;60(4):218-25. PMID: 20486473
Lv N, Kim EK, Song MY, et al. JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway. Exp Cell Res. 2009 Jul 15;315(12):2064-71. PMID: 19414010
Linwong W, Hirasawa N, Aoyama S, et al. Inhibition of the antigen-induced activation of rodent mast cells by putative Janus kinase 3 inhibitors WHI-P131 and WHI-P154 in a Janus kinase 3-independent manner. Br J Pharmacol. 2005 Jul;145(6):818-28. PMID: 15852029.
