WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200810
Description: CP-547632, also known as PAN-90806, is as a potent inhibitor of the VEGFR-2 and basic fibroblast growth factor (FGF) kinases (IC50 11 and 9 nM, respectively). It is selective relative to epidermal growth factor receptor, platelet-derived growth factor , and other related TKs. It also inhibits VEGF-stimulated autophosphorylation of VEGFR-2 in a whole cell assay with an IC50 value of 6 nM. After oral administration of CP-547,632 to mice bearing NIH3T3/H-ras tumors, VEGFR-2 phosphorylation in tumors was inhibited in a dose-dependent fashion (EC50 590 ng/ml). CP-547,632 is a well-tolerated, orally-bioavailable inhibitor presently under clinical investigation for the treatment of human malignancies.
MedKoo Cat#: 200810
Chemical Formula: C20H24BrF2N5O3S
Exact Mass: 531.07513
Molecular Weight: 532.4
Elemental Analysis: C, 45.12; H, 4.54; Br, 15.01; F, 7.14; N, 13.15; O, 9.02; S, 6.02
Synonym: CP547632; CP 547632; CP-547632; PAN90806; PAN 90806; PAN-90806; CP632; OSI632; CP 632; OSI 632; CP-632; OSI-632
IUPAC/Chemical Name: 3-((4-bromo-2,6-difluorobenzyl)oxy)-5-(3-(4-(pyrrolidin-1-yl)butyl)ureido)isothiazole-4-carboxamide
InChi Key: HXHAJRMTJXHJJZ-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H24BrF2N5O3S/c21-12-9-14(22)13(15(23)10-12)11-31-18-16(17(24)29)19(32-27-18)26-20(30)25-5-1-2-6-28-7-3-4-8-28/h9-10H,1-8,11H2,(H2,24,29)(H2,25,26,30)
SMILES Code: O=C(C1=C(NC(NCCCCN2CCCC2)=O)SN=C1OCC3=C(F)C=C(Br)C=C3F)N
Phase I/II trial results: Seventy patients were enrolled and 68 patients were treated, 37 in phase 1 and 31 in phase 2 (14 with the combination and 17 with chemotherapy alone). Dose-limiting toxicity of CP-547,632 250 mg by mouth daily in combination with paclitaxel and carboplatin was grade 3 rash and grade 3 diarrhea despite medical intervention. CP-547,632 did not significantly affect the pharmacologic profiles of paclitaxel and carboplatin. No subject had CR. In phase I, seven subjects (22.6%) had a confirmed partial response. In phase II, four subjects (28.6%) receiving CP-547,632 plus chemotherapy had a confirmed partial response. In the phase II chemotherapy alone group, four subjects (25%) had a confirmed partial response. CONCLUSION: The combination of CP-547,632 and paclitaxel and carboplatin was well-tolerated at doses up to 200 mg by mouth daily. Dose-limiting toxicity of CP-547,632 at 250 mg consisted of diarrhea and rash. CP-547,632 did not increase the objective response rate to chemotherapy alone in patients with advanced non-small cell lung cancer. (source: Cancer Chemother Pharmacol. 2007 Jun;60(1):81-9. Epub 2006 Oct 10.).
1: Cohen RB, Langer CJ, Simon GR, Eisenberg PD, Hainsworth JD, Madajewicz S, Cosgriff TM, Pierce K, Xu H, Liau K, Healey D. A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol. 2007 Jun;60(1):81-9. Epub 2006 Oct 10. PubMed PMID: 17031646.
2: Wakelee HA, Schiller JH. Targeting angiogenesis with vascular endothelial growth factor receptor small-molecule inhibitors: novel agents with potential in lung cancer. Clin Lung Cancer. 2005 Sep;7 Suppl 1:S31-8. Review. PubMed PMID: 16159417.
3: Beebe JS, Jani JP, Knauth E, Goodwin P, Higdon C, Rossi AM, Emerson E, Finkelstein M, Floyd E, Harriman S, Atherton J, Hillerman S, Soderstrom C, Kou K, Gant T, Noe MC, Foster B, Rastinejad F, Marx MA, Schaeffer T, Whalen PM, Roberts WG. Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy. Cancer Res. 2003 Nov 1;63(21):7301-9. PubMed PMID: 14612527.
4: Sridhar SS, Shepherd FA. Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer. Lung Cancer. 2003 Dec;42 Suppl 1:S81-91. Review. PubMed PMID: 14611919.
5: Shepherd FA, Sridhar SS. Angiogenesis inhibitors under study for the treatment of lung cancer. Lung Cancer. 2003 Aug;41 Suppl 1:S63-72. Review. PubMed PMID: 12867064.