Uses
WHI-P180 (Janex 3) is a multi-kinase inhibitor; inhibits RET, KDR and EGFR with IC50s of 5 nM, 66 nM and 4 μM, respectively.
in vivo
WHI-P180 is also an active inhibitor of IgE-mediated mast cell responses. The elimination half-life of WHI-P180 in CD-1 mice (BALB/c mice) following iv, ip, or po administration is less than 10 min. Systemic clearance of WHI-P180 is 6742 mL/h/kg in CD-I mice and 8188 mL/h/kg in BALB/c mice. Notably, WHI-P180, when administered in two consecutive nontoxic ip bolus doses of 25 mg/kg, inhibits IgE/antigen-induced vascular hyperpermeability in a well-characterized murine model of passive cutaneous anaphylaxis.
References
[1] Newton R, et al. The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity. Eur J Med Chem. 2016 Apr 13;112:20-32. DOI:
10.1016/j.ejmech.2016.01.039[2] Ghosh S, et al. 4-[3-Bromo-4-hydroxyphenyl)amino]-6,7-dimethoxyquinazolin-1-ium chloride methanol solvateand 4-[(3-hydroxyphenyl)amino]-6,7-dimethoxy-1-quinazolinium chloride. Acta Crystallogr C. 2001 Jan;57(Pt 1):76-8. DOI:
10.1107/s0108270100013561[3] Chen CL, et al. Pharmacokinetics and biologic activity of the novel mast cell inhibitor, 4-(3-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline in mice. Pharm Res. 1999 Jan;16(1):117-22. DOI:
10.1023/a:1018835232027
![Phenol, 3-[(6,7-diMethoxy-4-quinazolinyl)aMino]- Structure](https://www.chemicalbook.com/CAS/20150408/GIF/211555-08-7.gif)
