PD-161570

PD-161570 is a selective FGFR inhibitor (IC50 values are 40, 262 and 3700 nM for FGFR, PDGFR and EGFR respectively). PD 161570 had about 5- and 100-fold greater selectivity toward the FGF-1 receptor (IC50 = 40 nM) compared with the PDGFbeta receptor (IC50 = 262 nM) or EGF receptor (IC50 = 3.7 microM) tyrosine kinases, respectively. In addition, PD 161570 suppressed constitutive phosphorylation of the FGF-1 receptor in both human ovarian carcinoma cells (A121(p)) and Sf9 insect cells overexpressing the human FGF-1 receptor and blocked the growth of A121(p) cells in culture. The results demonstrate a novel synthetic inhibitor with nanomolar potency and specificity towards the FGF-1 receptor tyrosine kinase.

Product information

CAS Number: 192705-80-9

Molecular Weight: 532.51

Formula: C26H35Cl2N7O

Chemical Name: N-[6-(2,6-Dichlorophenyl)-2-[[4-(diethylamino)butyl]amino]pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)urea

Smiles: CC(C)(C)NC(=O)NC1=NC2=NC(NCCCCN(CC)CC)=NC=C2C=C1C1C(Cl)=CC=CC=1Cl

InChiKey: MKVMEJKNLUWFSQ-UHFFFAOYSA-N

InChi: InChI=1S/C26H35Cl2N7O/c1-6-35(7-2)14-9-8-13-29-24-30-16-17-15-18(21-19(27)11-10-12-20(21)28)23(31-22(17)32-24)33-25(36)34-26(3,4)5/h10-12,15-16H,6-9,13-14H2,1-5H3,(H3,29,30,31,32,33,34,36)

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO

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:

PD-161570 (Compound 6c; 0.1-1 µM; 1-8 days; VSMCs) treatment inhibits PDGF-stimulated vascular smooth muscle cell proliferation in a dose dependent fashion with an IC50 of 0.3 µM on day 8. PD-161570 suppresses constitutive phosphorylation of the FGF-1 receptor in both human ovarian carcinoma cells (A121(p)) and Sf9 insect cells overexpressing the human FGF-1 receptor and blocked the growth of A121(p) cells in culture. PD-161570 can potently inhibit basic fibroblast growth factor (bFGF)-mediated angiogenesis.

References:

1. Stevens DA, Harvey CB, Scott AJ, O'Shea PJ, Barnard JC, Williams AJ, Brady G, Samarut J, Chassande O, Williams GR. Thyroid hormone activates fibroblast growthfactor receptor-1 in bone. Mol Endocrinol. 2003 Sep;17(9):1751-66. PubMed PMID:12805413.
2. Wolfe A, O'Clair B, Groppi VE, McEwen DP. Pharmacologic characterization of akinetic in vitro human co-culture angiogenesis model using clinically relevantcompounds. J Biomol Screen. 2013 Dec;18(10):1234-45. doi:10.1177/1087057113502085. PubMed PMID: 24019254.
3. Batley BL, Doherty AM, Hamby JM, Lu GH, Keller P, Dahring TK, Hwang O,Crickard K, Panek RL. Inhibition of FGF-1 receptor tyrosine kinase activity by PD161570, a new protein-tyrosine kinase inhibitor. Life Sci. 1998;62(2):143-50.PubMed PMID: 9488112.

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