Brivanib, A novel dual VEGF-R2/bFGF-R inhibitor

Anticancer Research

Volumn 30, Issue 11, 2010, Pages 4477-4483

  Dempke, Wolfram C M ^a   Zippel, Roland ^a  

^a Elbland Clinic Riesa   (Germany)

Author keywords

Angiogenesis; bFGF R; Biomarker; Brivanib; Clinical studies; Review; VEGF R

Indexed keywords

1 TERT BUTYL 3 [6 (3,5 DIMETHOXYPHENYL) 2 (4 DIETHYLAMINOBUTYLAMINO)PYRIDO[2,3 D]PYRIMIDIN 7 YL]UREA; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 MORPHOLINO 8 PHENYLCHROMONE; 2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 3 (4 BROMO 2,6 DIFLUOROBENZYLOXY) 5 [3 [4 (1 PYRROLIDINYL)BUTYL]UREIDO] 4 ISOTHIAZOLECARBOXAMIDE; 5,6,7,13 TETRAHYDRO 12 (3 HYDROXYPROPYL) 9 ISOPROPOXYMETHYLINDENO[2,1 A]PYRROLO[3,4 C]CARBAZOL 5(12H) ONE DIMETHYLGLYCINE ESTER; AE 941; AXITINIB; BEVACIZUMAB; BMS 690514; BRIVANIB; BRIVANIB ALANINATE; CEDIRANIB; CETUXIMAB; DOVITINIB; E 7080; INTEDANIB; IRINOTECAN; LINIFANIB; MOTESANIB; OSI 930; PAZOPANIB; SORAFENIB; SUNITINIB; TIVOZANIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; VATALANIB;

ANGIOGENESIS; ANOREXIA; ANTINEOPLASTIC ACTIVITY; BLEEDING; BLOOD VESSEL; CANCER RESISTANCE; CANCER THERAPY; COLORECTAL CANCER; DIARRHEA; DRUG ABSORPTION; DRUG METABOLISM; DRUG POTENTIATION; FATIGUE; HUMAN; LOADING DRUG DOSE; MUSCLE HYPERTONIA; NAUSEA; NONHUMAN; PRIORITY JOURNAL; RASH; REVIEW; SINGLE DRUG DOSE; THROMBOEMBOLISM; TUMOR GROWTH; VOMITING;

CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASMS; PYRROLES; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; TRIAZINES; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 78650240625     PISSN: 02507005     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (27)

1. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27-31, 1995.
2. Risau W: Mechanisms of angiogenesis. Nature 386: 671-674, 1997.
3. Saharinen P, Tammela T, Karkkainen MJ and Alitalo K: Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation. Trends Immunol 25: 387-395, 2004. (Pubitemid 38780956)
4. Ribatti D, Nico B, Crivellato E, Roccaro AM and Vacca A: The history of the angiogenic switch concept. Leukemia 21: 44-52, 2007.
5. Youssoufian H, Hicklin DJ and Rowinsky EK: Review: Monoclonal antibodies to the vascular endothelial growth factor receptor-2 in cancer therapy. Clin Cancer Res 18(Suppl): 5544s-5548s, 2007. (Pubitemid 47510385)
6. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS and Dvorak HF: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219: 983-985, 1983.
7. Alitalo K and Carmeliet P: Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 3: 219-227, 2002.
8. Hicklin DJ and Ellis LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23: 1011-1027, 2005. (Pubitemid 46202320)
9. Kerbel RS: Tumor angiogenesis. N Engl J Med 358: 2039-2049, 2008.
10. Dempke W and Heinemann V: Resistance to EGF-R (erbB-1) and VEGF-R modulating agents. Eur J Cancer 45: 1117-1128, 2009.
11. Tassi E and Wellstein A: The angiogenetic switch molecule, secreted FDF-binding protein, an inhibitor of early stages of pancreatic and colorectal adenocarcinoma. Semin Oncol 66: 50-56, 2006.
12. Blanckaert VD, Hebbar M, Louchez MM, Vilain MO, Schelling ME and Peyrat JP: Basic fibroblast growth factor receptors and their prognostic value in human breast cancer. Clin Cancer Res 4: 2939-2947, 1998. (Pubitemid 29001465)
13. Jaye M, Schlessinger J and Dionne C: FGF receptor tyrosine kinases: molecular analysis and signal transduction. Biochim Biophys Acta 1135: 185-199, 1992.
14. Deudero JJ, Caramelo C, Castellanos MC, Neria F, Fernández- Sánchez R, Calabia O, Peñate S and González-Pacheco FR: Induction of hypoxia-inducible factor 1alpha gene expression by vascular endothelial growth factor. J Biol Chem 283: 11435-11444, 2008.
15. Casanovas O, Hicklin DJ, Bergers G and Hanahan D: Drug resistance by evasion of antiangiogenetic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8: 299-309, 2005. (Pubitemid 41443415)
16. Nissen LJ, Cao R, Hedlung EM, Wang Z, Zhao X, Wetterskog D, Funa K, Bråkenhielm E and Cao Y: Angiogenetic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J Clin Invest 117: 2766-2777, 2007.
17. Shi YH, B ingle L, Gong LH, Wang YX, Corke KP and Fang WG: Basic FGF augments hypoxia-induced HIF-1-alpha expression and VEGF release in T47D breast cancer cells. Pathology 39: 396-400, 2007.
18. Huynh H, Ngo VC, Fargnoli J, Ayers M, Soo KC, Koong HN, Thng CH, Ong HS, Chung A, Chow P, Pollock P, Byron S and Tran E: Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res 14: 6146-6153, 2008.
19. Cai ZW, Zhang YZ, Borzirelli RM, Qian L, Barbosa S, Wei D, Zheng X, Wu L, Fan J, Shi Z, Wautlet BS, Mortillo S, Jeyaseelan R Sr, Kukral DW, Kamath A, Marathe P, D'Arienzo C, Derbin G, Barrish JC, Robl JA, Hunt JT, Lombardo LJ, Fargnoli J and Bhide RS: Discovery of brivanib alaninate ((S)-((R)-1-(4-(4- fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy) propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215). J Med Chem 51: 1976-1980, 2008.
20. Jonker DJ, Rosen LS, Sawyer M, Zhang YZ and Borzirelli RM: A phase I study of BMS-582664 (brivanib alaninate), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in patients (pts) with advanced/metastatic solid tumors: safety, pharmacokinetic (PK), and pharmacodynamic (PD) findings. J Clin Oncol 25(Suppl): 3559, 2007.f
21. Garrett CR, Siu L, El-Khoueiry A, Zhang YZ and Borzirelli RM: A phase I study of BMS-582664 (brivanib alaninate), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full-dose cetuximab in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy. J Clin Oncol 26(Suppl): 4111, 2008.
22. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R and Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355: 2542-2550, 2006. (Pubitemid 44917502)
23. http://www.clinicaltrial.gov
24. Park JW, Walters IB, Raoul JC, Zhang YZ and Borzirelli RM: A phase 2 open-label study of brivanib alaninate in patients with hepatocellular carcinoma. ILCA Meeting, Chicago (USA), Abstract 0-013, 2008.
25. Dupont E, Falardeau P, Mousa SA, Dimitriadou V, Pepin MC, Wang T and Alaoui-Jamali MA: Antiangiogenetic and antimetastatic properties of neovastat (AE-941), an orally active extract derived from cartilage tissue. Clin Exp Metastasis 19: 145-154, 2002.
26. Jubb AM, Oates AJ, Holden S and Koeppen H: Predicting benefit from antiangiogenetic agents in malignancy. Nat Rev Cancer 6: 626-635, 2006.
27. Ayers M, Fargnoli J, Lewin A, Wu Q and Platero JS: Discovery and validation of biomarkers that respond to treatment with brivanib alaninate, a small-molecule VEGFR-2/FGFR-2 antagonist. Cancer Res 67: 6877-6906, 2007.