PD 166285-CAS 212391-63-4-Calbiochem

C₂₆H₂₇Cl₂N₅O₂ · 2HCl

585.35

A cell-permeable, orally bioavailable, ATP-competitive, broad-spectrum tyrosine kinase inhibitor (IC₅₀ against against c-Src, Wee1, FGFR-1, Myt1, EGFR, and PDGFRβ = 8.4, 24, 39.3, 72, 87.5 and 98.3 nM, respectively) that suppresses angiogenesis both in vitro (max inhibition dose at 100 nM in HUVEC microcapillary formation assays) and in vivo (max inhibition achieved via 5 mg/kg p.o. in murine Matrigel plug angiogenesis assays), while exhibiting much reduced potency against Chk1, MAPK, and PKC (IC₅₀ = 3.4, 5, and 22.7 µM, respectively) and little activity toward IRTK and Cdk4/D1 even at concentrations as high as 50 µM. Shown to effectively block PDGF-, EGF-, and bFGF-stimulated receptor phosphorylations (IC₅₀ = 6.5, 1600, and 97.3 nM, respectively) and other cellular responses in rat aortic smooth muscle cells. Inhibition of cellular Wee1 activity by 500 nM PD 166285 in combination with 50 ng/ml nocodazole (Cat. No. 487928) treatment is also reported to result in a blockage of radiation-induced Cdc2 phosphorylation on Tyr15 and Thr14 in 7 human cancer cells and specifically demonstrated to sensatize PA-1 cultures to radiation-induced cell death in a p53-dependent manner.
A cell-permeable, orally bioavailable, ATP-competitive, broad-spectrum tyrosine kinase inhibitor (IC₅₀ against against c-Src, Wee1, FGFR-1, Myt1, EGFR, and PDGFRβ = 8.4, 24, 39.3, 72, 87.5 and 98.3 nM, respectively) that suppresses angiogenesis both in vitro (max inhibition dose at 100 nM in HUVEC microcapillary formation assays) and in vivo (max inhibition achieved via 5 mg/kg p.o. in murine Matrigel plug angiogenesis assays), while exhibiting much reduced potency against Chk1, MAPK, and PKC (IC₅₀ = 3.4, 5, and 22.7 µM, respectively) and little activity toward IRTK and Cdk4/D1 even at concentrations as high as 50 µM. Shown to effectively block PDGF-, EGF-, and bFGF-stimulated receptor phosphorylations (IC₅₀ = 6.5, 1600, and 97.3 nM, respectively) and other cellular responses in rat aortic smooth muscle cells. Inhibition of cellular Wee1 activity by 500 nM PD 166285 in combination with 50 ng/ml nocodazole (Cat. No. 487928) treatment is also reported to result in a blockage of radiation-induced Cdc2 phosphorylation on Tyr15 and Thr14 in 7 human cancer cells and specifically demonstrated to sensatize PA-1 cultures to radiation-induced cell death in a p53-dependent manner.

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Wang, Y., et al. 2001. Cancer Res.61, 8211.
Dimitroff, C.J., et al. 1999. Invest. New Drugs17, 121.
Roginskaya, V., et al. 1999. Leukemia13, 855.
Panek, R.L., et al. 1997. J. Pharmacol. Exp. Ther.283, 1433.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

100

≥97% (HPLC)

solid

Calbiochem^®

OK to freeze
desiccated (hygroscopic)
protect from light

pale yellow

DMSO: 50 mg/mL

ambient

2-8℃

Packaged under inert gas

11 - Combustible Solids

WGK 3