513028

PD 166285

A cell-permeable, orally bioavailable, ATP-competitive, broad-spectrum tyrosine kinase inhibitor that suppresses angiogenesis both in vitro and in vivo.

• Synonym(s): PD 166285, PD166285, PD0166285, 6-(2,6-Dichlorophenyl)-2-(4-(2-(diethylaminoethoxy)-phenylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one, 2HCl, PDGFR Tyrosine Kinase Inhibitor XIX, Wee1 Inhibitor IV, PDGFR Tyrosine Kinase Inhibitor XIX, Wee1 Inhibitor IV, 6-(2,6-Dichlorophenyl)-2-(4-(2-(diethylaminoethoxy)-phenylamino)-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one, 2HCl, PD166285, PD0166285
• Empirical Formula (Hill Notation): C₂₆H₂₇Cl₂N₅O₂ · 2HCl
• CAS Number: 212391-63-4
• Molecular Weight: 585.35
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• Assay: ≥97% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated (hygroscopic); protect from light
• color: pale yellow
• solubility: DMSO: 50 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• InChI: 1S/C26H27Cl2N5O2.2ClH/c1-4-33(5-2)13-14-35-19-11-9-18(10-12-19)30-26-29-16-17-15-20(25(34)32(3)24(17)31-26)23-21(27)7-6-8-22(23)28;;/h6-12,15-16H,4-5,13-14H2,1-3H3,(H,29,30,31);2*1H
• InChI key: NADLBPWBFGTESN-UHFFFAOYSA-N

Description

General description

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.

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

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.

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable