PF-04217903 phenolsulfonate

PF-04217903 phenolsulfonate is a potent ATP-competitive c-Met kinase inhibitor with Ki of 4.8 nM for human c-Met. PF-04217903 phenolsulfonate shows more than 1,000-fold selectivity relative to 208 kinases. Antiangiogenic properties.

Product information

CAS Number: 1159490-85-3

Molecular Weight: 546.56

Formula: C25H22N8O5S

Chemical Name: 2-(4-{1-[(quinolin-6-yl)methyl]-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl}-1H-pyrazol-1-yl)ethan-1-ol; 4-hydroxybenzene-1-sulfonic acid

Smiles: OC1C=CC(=CC=1)S(O)(=O)=O.OCCN1C=C(C=N1)C1=CN=C2N=NN(CC3C=C4C=CC=NC4=CC=3)C2=N1

InChiKey: IVOMZNMWVCWDBF-UHFFFAOYSA-N

InChi: InChI=1S/C19H16N8O.C6H6O4S/c28-7-6-26-12-15(9-22-26)17-10-21-18-19(23-17)27(25-24-18)11-13-3-4-16-14(8-13)2-1-5-20-16;7-5-1-3-6(4-2-5)11(8,9)10/h1-5,8-10,12,28H,6-7,11H2;1-4,7H,(H,8,9,10)

Technical Data

Appearance: Solid Power

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

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: ≥12 months 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:

PF-04217903 phenolsulfonate (0.1-10000 nM; 48-72 hours) inhibits proliferation of c-Met–amplified human GTL-16 gastric carcinoma and H1993 NSCLC cells with IC50 values of 12 and 30 nM, respectively. PF-04217903 phenolsulfonate (1.5-3333 nM; 48 hours) induces apoptosis of GTL-16 cells (IC50=31 nM). PF-04217903 phenolsulfonate also inhibits HGF-mediated cell migration and Matrigel invasion in several c-Met–overexpressing tumor cell lines such as human NCI-H441 lung carcinoma and HT29 colon carcinoma with IC50 values comparable with those for inhibition of c-Met phosphorylation in these cell lines (IC50=7-12.5 nM). PF-04217903 phenolsulfonate displays similar potency to inhibit the activity of c-Met-H1094R, c-Met-R988C, and c-Met-T1010I with IC50 of 3.1 nM, 6.4 nM, and 6.7 nM, respectively. PF-04217903 phenolsulfonate has no inhibitory activity against c-Met-Y1230C with IC50 of >10 μM.

In Vivo:

PF-04217903 phenolsulfonate (1-30 mg/kg; p.o.; daily for 16 days) shows dose-dependent tumor growth inhibition, which correlated with the inhibition in c-Met phosphorylation in these tumors. PF-04217903 phenolsulfonate (5-50 mg/kg, p.o.; once daily for 3 days) dose dependently inhibits c-Met, Gab-1, Erk1/2, and AKT phosphorylation and induced apoptosis (cleaved caspase-3) in U87MG xenograft tumors at all dose levels. PF-04217903 phenolsulfonate shows a significant dose-dependent reduction of human IL-8 levels in both the U87MG and GTL-16 models and decreases human VEGFA levels in the GTL-16 model. PF-04217903 phenolsulfonate strongly induces phospho-PDGFRβ levels in U87MG xenograft tumors.

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