WHI-P154

WHI-P154 is a JAK3 inhibitor with IC50 = 1.8 microM. WHI-P154 displays no activity at JAK1 or JAK2. WHI-P154 also Inhibits STAT1 activation, iNOS expression and NO production in macrophages in vitro . Also inhibits other common kinases including EGFR (IC50 = 4 nM), Src, Abl, VEGFR, MAPK and PI 3-K and induces apoptosis in human glioblastoma cell lines (IC50 = 158 microM).

Product information

CAS Number: 211555-04-3

Molecular Weight: 376.20

Formula: C16H14BrN3O3

Synonym:

Janex1

Chemical Name: 2-Bromo-4-[(6,7-dimethoxy-4-quinazolinyl)amino]phenol

Smiles: COC1=CC2=C(NC3=CC(Br)=C(O)C=C3)N=CN=C2C=C1OC

InChiKey: CBIAKDAYHRWZCU-UHFFFAOYSA-N

InChi: InChI=1S/C16H14BrN3O3/c1-22-14-6-10-12(7-15(14)23-2)18-8-19-16(10)20-9-3-4-13(21)11(17)5-9/h3-8,21H,1-2H3,(H,18,19,20)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

WHI-P154 is a potent EGFR inhibitor, and also modestly blocks JAK3, with IC50s of 4 nM and 1.8 μM, respectively[1]. WHI-P154 significantly enhances the sensitivity of ABCG2-overexpressing cells to its substrates. WHI-P154 (4 μM) moderately sensitizes ABCB1-overexpressing KB-C2 cells to its substrates whereas shows no sensitizing effect on ABCC1-, ABCC2 or ABCC10-mediated drug resistance. Moreover, WHI-P154 (4 μM) causes a significant increase in the intracellular accumulation of [3H]-mitoxantrone in ABCG2-overexpressing cells. WHI-P154 alters the expression levels rather than the localization of the ABCG2 protein in ABCG2-overexpressing cells.

References:

1. Zhang H, Zhang YK, Wang YJ, Kathawala RJ, Patel A, Zhu H, Sodani K, Talele TT, Ambudkar SV, Chen ZS, Fu LW. WHI-P154 Enhances the Chemotherapeutic Effect of Anticancer Agents in ABCG2-overexpressing Cells. Cancer Sci. 2014 Jun 5. doi: 10.1111/cas.12462. [Epub ahead of print] PubMed PMID: 24903205.
2. Richards GR, Smith AJ, Cuddon P, Ma QP, Leveridge M, Kerby J, Roderick HL, Bootman MD, Simpson PB. The JAK3 inhibitor WHI-P154 prevents PDGF-evoked process outgrowth in human neural precursor cells. J Neurochem. 2006 Apr;97(1):201-10. Epub 2006 Mar 3. PubMed PMID: 16515549.
3. Linwong W, Hirasawa N, Aoyama S, Hamada H, Saito T, Ohuchi K. 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. PubMed PMID: 15852029; PubMed Central PMCID: PMC1576194.

Products are for research use only. Not for human use.