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 Property

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)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H360May damage fertility or the unborn child

H361Suspected of damaging fertility or the unborn child

H373May cause damage to organs through prolonged or repeated exposure

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P281Use personal protective equipment as required.

P308+P313IF exposed or concerned: Get medical advice/attention.

P314Get medical advice/attention if you feel unwell.

P405Store locked up.

P501Dispose of contents/container to..…

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 Chemical Properties,Usage,Production

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

target

VEGFR-2

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.