JAK3 INHIBITOR I

WHI-P131 (202475-60-3) is a JAK3 inhibitor.Inhibits human glioblastoma cell adhesion and invasion.1 Increases survival in a mouse ALS model.2 Delays or prevents autoimmune type 1 diabetes in NOD mice.3 Exhibits potent anti-inflammatory activity in mouse models of peritonitis, colitis, cellulitis and systemic inflammatory response syndrome.4 Displays protective effects against myocardial ischemia and reperfusion injury in mouse models.5

Janex 1 is a Janus tyrosine kinase 3 (JAK3) inhibitor. Inhibition of JAK3 has been shown to exhibit protective action against the development of T1D in non-obese diabetic (NOD) mice. Janex 1 has been shown to suppresses proliferation of short-term cultured NOD CD4+ T cells through induction of apoptosis, while promoting survival of a particular population of long-term cultured cells. It ameliorates the expression of TNF-α-induced cell adhesion molecules and improves myocardial vascular permeability.

JAK3: 78 μM (IC₅₀)

WHI-P131 is a potent and selective inhibitor of Janus kinase 3 and glioblastoma cell adhesion and migration. This novel quinazoline derivative inhibits the enzymatic activity of constitutively active Jak3 without affecting Jak1, Jak2, or other family tyrosine kinases. WHI-P131 has also been shown to inhibit thrombin-induced tyrosine phosphorylation of Stat1 and Stat3. These properties make this compound useful when studying different diseases such as acute lymphoblastic leukemia, glioblastoma multiforme, and thromboembolism.

[1] R K NARLA. Inhibition of human glioblastoma cell adhesion and invasion by 4-(4’-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3’-bromo-4’-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154).[J]. Clinical Cancer Research, 1998, 4 10: 2463-2471.
[2] VUONG N. TRIEU . A Specific Inhibitor of Janus Kinase-3 Increases Survival in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis[J]. Biochemical and biophysical research communications, 2000, 267 1: Pages 22-25. DOI:10.1006/bbrc.1999.1905
[3] MARINA CETKOVIC-CVRLJE . Targeting JAK3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice[J]. Clinical immunology, 2003, 106 3: Pages 213-225. DOI:10.1016/s1521-6616(02)00049-9
[4] FATIH M. UCKUN . Anti-inflammatory activity profile of JANEX-1 in preclinical animal models[J]. Bioorganic & Medicinal Chemistry, 2008, 16 3: Pages 1287-1298. DOI:10.1016/j.bmc.2007.10.066
[5] YOUNG-BIN OH. Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice[J]. Experimental and Molecular Medicine, 2013, 45 5: e23-e23. DOI:10.1038/emm.2013.43