WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200533
Description: BMS-690514 is a potent inhibitor of human epidermal growth factor receptor (HER) 1 (EGFR), 2, and 4, and vascular endothelial growth factor receptors (VEGFR) 1-3. BMS-690514 is currently under investigation as an oral agent for the treatment of solid tumors. In vitro and in vivo studies were conducted to characterize the pharmacokinetics and metabolism. Through integration of in vitro and in vivo pharmacokinetic data and antitumor efficacy in nude mice, human pharmacokinetics and efficacious doses were projected for BMS-690514. The oral bioavailability of BMS-690514 was 78% in mice, approximately 100% in rats, 8% in monkeys, and 29% in dogs. The low oral bioavailability in monkeys could be attributed to high systemic clearance in that species, which was also consistent with predicted clearance using in vitro data from monkey liver microsomes. The preclinical ADME properties of BMS-690514 suggest good oral bioavailability in humans and metabolism by multiple pathways including oxidation and glucuronidation.
MedKoo Cat#: 200533
Chemical Formula: C19H24N6O2
Exact Mass: 368.19607
Molecular Weight: 368.43
Elemental Analysis: C, 61.94; H, 6.57; N, 22.81; O, 8.69
Synonym: BMS690514; BMS 690514; BMS-690514.
IUPAC/Chemical Name: (3R,4R)-4-Amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol
InChi Key: CSGQVNMSRKWUSH-IAGOWNOFSA-N
InChi Code: InChI=1S/C19H24N6O2/c1-27-15-4-2-3-14(9-15)23-19-18-13(5-8-25(18)22-12-21-19)10-24-7-6-16(20)17(26)11-24/h2-5,8-9,12,16-17,26H,6-7,10-11,20H2,1H3,(H,21,22,23)/t16-,17-/m1/s1
SMILES Code: O[C@@H]1CN(CC2=C3C(NC4=CC=CC(OC)=C4)=NC=NN3C=C2)CC[C@H]1N
1: Hong H, Su H, Sun H, Allentoff A, Ekhato IV, Chando T, Caceres-Cortes J, Roongta V, Iyer RA, Humphreys WG, Christopher LJ. Metabolism and Disposition of [14C]BMS-690514 ((3R,4R)-4-amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f][1,2,4]triazin-5-yl) methyl)-3-piperidinol) Following Oral Administration to Rats, Rabbits and Dogs. Drug Metab Dispos. 2010 Apr 2. [Epub ahead of print] PubMed PMID: 20363952.
2: Marathe P, Tang Y, Sleczka B, Rodrigues D, Gavai A, Wong T, Christopher L, Zhang H. Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Feb 17. [Epub ahead of print] PubMed PMID: 20166197.
3: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Dec;31(10):661-700. PubMed PMID: 20140276.
4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 May;31(4):263-98. PubMed PMID: 19557204.
5: Pennell NA, Lynch TJ Jr. Combined inhibition of the VEGFR and EGFR signaling pathways in the treatment of NSCLC. Oncologist. 2009 Apr;14(4):399-411. Epub 2009 Apr 8. Review. PubMed PMID: 19357226.
6: de La Motte Rouge T, Galluzzi L, Olaussen KA, Zermati Y, Tasdemir E, Robert T, Ripoche H, Lazar V, Dessen P, Harper F, Pierron G, Pinna G, Araujo N, Harel-Belan A, Armand JP, Wong TW, Soria JC, Kroemer G. A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib. Cancer Res. 2007 Jul 1;67(13):6253-62. PubMed PMID: 17616683.