WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200569
Description: Brivanib is the hydrolyzed form of Brivanib alaninate, which is a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2, a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells; inhibition of VEGFR2 may result in inhibition of tumor angiogenesis, inhibition of tumor cell growth, and tumor regression.
MedKoo Cat#: 200569
Chemical Formula: C19H19FN4O3
Exact Mass: 370.14412
Molecular Weight: 370.37756
Elemental Analysis: C, 61.61; H, 5.17; F, 5.13; N, 15.13; O, 12.96
Synonym: BMS540215; BMS-540215; BMS 540215.
IUPAC/Chemical Name: (R)-1-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)oxy)propan-2-ol
InChi Key: WCWUXEGQKLTGDX-LLVKDONJSA-N
InChi Code: InChI=1S/C19H19FN4O3/c1-10-6-13-14(23-10)4-5-15(17(13)20)27-19-18-12(3)16(26-8-11(2)25)7-24(18)22-9-21-19/h4-7,9,11,23,25H,8H2,1-3H3/t11-/m1/s1
SMILES Code: C[C@@H](O)COC1=CN2N=CN=C(OC3=C(F)C4=C(NC(C)=C4)C=C3)C2=C1C
Brivanib has a favorable cytochrome P450 profile and a low potential for drug-drug interactions. It inhibits growth of various solid carcinomas including hepatocellular carcinoma (HCC) xenografts in vivo. Brivanib-induced growth inhibition is associated with inhibition of angiogenesis and cell proliferation, and increased apoptosis. In phase I studies in patients with advanced or metastatic solid tumors, brivanib was well tolerated and had antitumor activity. In the phase II, open-label study, brivanib demonstrated promising efficacy and tolerability in patients with unresectable locally advanced or metastatic HCC as both first- and second-line treatment after exposure to prior therapy, including other antiangiogenics. As a result of these data, brivanib is in phase III development in HCC and in combination with other agents for treatment of various tumors, including colorectal cancer. [ source: Huynh, H., Fargnoli, J. Brivanib alaninate, Drugs of the Future, 2009, 34(11): 88 1)
Phase II study of Brivanib. Between March 2007 and May 2009, 55 patients were treated and were evaluable for response. Patients were assessed using modified World Health Organization (mWHO) criteria. According to mWHO criteria and as assessed by Independent Response Review Committee, the six-month progression-free survival rate (95% CI) was 18.2% (9.1%-30.9%). Median progression-free survival (95% CI) was 2.7 months (1.4-3.0). One patient achieved a complete response and three achieved a partial response. Twenty-two had stable disease. Median overall survival (95% CI) was 10 (6.8-15.2) months. Brivanib was generally well tolerated; the most common adverse events included fatigue, hypertension, and diarrhea. Brivanib as first-line therapy demonstrates promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC. (source: Clin Cancer Res. 2011 Apr 1;17(7):1973-83).
1: Finn RS, Kang YK, Mulcahy M, Polite BN, Lim HY, Walters I, Baudelet C, Manekas D, Park JW. Phase II, Open-label Study of Brivanib as Second-line Therapy in Patients with Advanced Hepatocellular Carcinoma. Clin Cancer Res. 2012 Jan 11. [Epub ahead of print] PubMed PMID: 22238246.
2: Gong J, Gan J, Iyer RA. Identification of the oxidative and conjugative enzymes involved in the biotransformation of brivanib. Drug Metab Dispos. 2012 Jan;40(1):219-26. Epub 2011 Oct 11. PubMed PMID: 21989950.
3: Garcia JA, Roberts LR. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. J Hepatol. 2011 Sep 29. [Epub ahead of print] PubMed PMID: 21963517.
4: Kudo M. Future treatment option for hepatocellular carcinoma: a focus on brivanib. Dig Dis. 2011;29(3):316-20. Epub 2011 Aug 9. Review. PubMed PMID: 21829023.
5: Syed S, Clemens PL, Lathers D, Kollia G, Dhar A, Walters I, Masson E. Lack of Effect of Brivanib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, Administered Intravenously and Orally in Healthy Participants. J Clin Pharmacol. 2011 Jun 9. [Epub ahead of print] PubMed PMID: 21659627.
6: Garrett CR, Siu LL, El-Khoueiry A, Buter J, Rocha-Lima CM, Marshall J, LoRusso P, Major P, Chemidlin J, Mokliatchouk O, Velasquez L, Hayes W, Feltquate D, Syed S, Ford S, Kollia G, Galbraith S, Nuyten DS. Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy. Br J Cancer. 2011 Jun 28;105(1):44-52. doi: 10.1038/bjc.2011.182. Epub 2011 May 31. PubMed PMID: 21629245; PubMed Central PMCID: PMC3137402.
7: Allen E, Walters IB, Hanahan D. Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin Cancer Res. 2011 Aug 15;17(16):5299-310. doi: 10.1158/1078-0432.CCR-10-2847. Epub 2011 May 27. PubMed PMID: 21622725; PubMed Central PMCID: PMC3156934.
8: LoRusso P, Shapiro GI, Hurwitz H, Pilat MJ, Chemidlin J, Kollia G, Syed S, Fischer B, Masson E. Lack of food effect on single-dose pharmacokinetics of brivanib, and safety and efficacy following multiple doses in subjects with advanced or metastatic solid tumors. Cancer Chemother Pharmacol. 2011 Dec;68(6):1377-85. Epub 2011 Apr 3. PubMed PMID: 21461891.
9: Diaz-Padilla I, Siu LL. Brivanib alaninate for cancer. Expert Opin Investig Drugs. 2011 Apr;20(4):577-86. Epub 2011 Mar 11. Review. PubMed PMID: 21391890.
10: Park JW, Finn RS, Kim JS, Karwal M, Li RK, Ismail F, Thomas M, Harris R, Baudelet C, Walters I, Raoul JL. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1973-83. Epub 2011 Feb 24. PubMed PMID: 21349999.