Brivanib
Brivanib Basic information
- Product Name:
- Brivanib
- Synonyms:
-
- 1-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-2-propanol
- (R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo(2,1-F)(1,2,4)triazin-6-yloxy)propan-2-ol
- 2-Propanol, 1-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-5-methylpyrrolo(2,1-F)(1,2,4)triazin-6-yl)oxy)-, (2R)-
- Bms 540215
- Bms540215
- Unii-ddu33B674i
- 1-[4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-propan-2(R)-ol
- (R)-1-(4-(4-Fluoro-2-Methyl-1H-indol-5-yloxy)-5-Methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol
- CAS:
- 649735-46-6
- MF:
- C19H19FN4O3
- MW:
- 370.38
- Product Categories:
-
- Inhibitors
- Mol File:
- 649735-46-6.mol
Brivanib Chemical Properties
- Density
- 1.42
- storage temp.
- Store at -20°C
- solubility
- insoluble in H2O; ≥18.5 mg/mL in DMSO; ≥3.39 mg/mL in EtOH with ultrasonic
- form
- Yellow powder.
- pka
- 14.18±0.20(Predicted)
- color
- White to light brown
Brivanib Usage And Synthesis
Uses
Brivanib is an ATP-competitive inhibitor against human VEGFR2 and FGFR with IC50 of 25 nM and 148 nM, respectively.
Definition
ChEBI: Brivanib is a secondary alcohol resulting from the hydrolysis of the carboxylic ester group of brivanib alaninate. It is a dual VEGFR-2/FGFR-1 kinase inhibitor whose alanine prodrug, brivanib alaninate is currently under development as an oral agent for the treatment of cancer. It has a role as an antineoplastic agent, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, an angiogenesis inhibitor, an apoptosis inducer, a fibroblast growth factor receptor antagonist and a drug metabolite. It is a pyrrolotriazine, a fluoroindole, a diether, an aromatic ether and a secondary alcohol.
Biological Activity
brivanib is an atp competitive inhibitor of human vegfr-2 with ic50 value of 25nm [1].brivanib is a selective rtk inhibitor that targets signaling via vegfr2 and 3, and fgfr1, 2 and 3. targeting both vegf and fgf signaling pathways inhibits tumor growth in rt2 mice, with vegf signaling predominating in initiation of tumor angiogenesis, currently, brivanib therapy is being evaluated in phase iii
in vivo
Brivanib displays antitumor activities in H3396 xenograft in athymic mice. At a dose of 60 and 90 mg/kg (p.o.), brivanib completely inhibits the tumor growth, with TGI of 85% and 97%, respectively[1]. Moreover, brivanib significantly suppresses tumor growth in Hepatocellular carcinoma (HCC) xenografts, which due to the decrease in phosphorylation of VEGFR2. The results show that the tumor weights in 06-0606 xenograft mice are 55% and 13%, compared with the controls at a dose of 50 mg/kg and 100 mg/kg. Brivanib is suggested to be efficient in treatment of HCC[2]. Brivanib (50 mg/kg, p.o.) attenuates liver fibrosis and stellate cell activation induced by BDL in mice. Brivanib inhibits growth factor and growth factor receptor mRNA expression in sham control animals but shows variable effects in bile duct ligated animals[3].
target
VEGFR-2
IC 50
VEGFR2: 25 nM (IC50)
References
[1] rajeev s. bhide, zhen-wei cai, yong-zheng zhang, ligang qian, donna wei, stephanie barbosa, louis j. lombardo, robert m. borzilleri, xiaoping zheng, laurence i. wu, joel c. barrish, soong-hoon kim, kenneth leavitt, arvind mathur, leslie leith, sam chao, barri wautlet, steven mortillo, robert jeyaseelan sr., daniel kukral, john t. hunt, amrita kamath, aberra fura, viral vyas, punit marathe, celia d’arienzo, george derbin, and joseph fargnoli. discovery and preclinical studies of (r)-1-(4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol (bms-540215), an in vivo active potent vegfr-2 inhibitor. journal of medicinal chemistry. 2006, 49 (7): 2143-2146.
[2] elizabeth allen, ian b. walters, and douglas hanahan. 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. clinical cancer research. 2011 (17): 5299-5310.
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