905281-76-7 Usage
Uses
GDC 0879 is a potent B-Raf inhibitor.
Biological Activity
gdc-0879 is synthsized as a potent and selective b-raf inhibitor. the raf/mitogen-activated protein kinase kinase (mek)/extracellular signal-regulated kinase signaling pathway is reported to be involved in cellular responses, which is relevant to tumorigenesis.
in vitro
gdc-0879 is a b-raf inhibitor against various in vitro and cell-based assays, such as a375 melanoma and colo205 colorectal carcinoma cell lines, both of which are v600e b-raf mutant. when screened against a panel of 140 kinases at its efficaciou dose, gdc-0879 showed expected activity only against c-raf [1].
in vivo
in mice treated by gdc-0879, both cell line-and patient-derived brafv600e tumors exhibited stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared with mutant kras-expressing tumors. moreover, it was found that the responsiveness of brafv600e melanoma cells to gdc-0879 could be dramatically altered by pharmacologic and genetic modulation of phosphatidylinositol 3-kinase pathway activity [2].
IC 50
0.13 nm against purified b-raf v600e enzyme; a cellular perk ic50 of 63 nm in the malme-3m cell line
references
[1] wong h, belvin m, herter s, hoeflich kp, murray lj, wong l, choo ef. pharmacodynamics of 2-[4-[(1e)-1-(hydroxyimino)-2,3-dihydro-1h-inden-5-yl]-3-(pyridine-4-yl)-1h-pyrazol-1-yl]ethan-1-ol (gdc-0879), a potent and selective b-raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy. j pharmacol exp ther. 2009 apr;329(1):360-7. [2] hoeflich kp, herter s, tien j, wong l, berry l, chan j, o'brien c, modrusan z, seshagiri s, lackner m, stern h, choo e, murray l, friedman ls, belvin m. antitumor efficacy of the novel raf inhibitor gdc-0879 is predicted by brafv600e mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression. cancer res. 2009 apr 1;69(7):3042-51.
Check Digit Verification of cas no
The CAS Registry Mumber 905281-76-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,0,5,2,8 and 1 respectively; the second part has 2 digits, 7 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 905281-76:
(8*9)+(7*0)+(6*5)+(5*2)+(4*8)+(3*1)+(2*7)+(1*6)=167
167 % 10 = 7
So 905281-76-7 is a valid CAS Registry Number.
InChI:InChI=1/C19H18N4O2/c24-10-9-23-12-17(19(21-23)13-5-7-20-8-6-13)15-1-3-16-14(11-15)2-4-18(16)22-25/h1,3,5-8,11-12,24-25H,2,4,9-10H2/b22-18+
905281-76-7Relevant articles and documents
Potent and selective pyrazole-based inhibitors of B-Raf kinase
Hansen, Joshua D.,Grina, Jonas,Newhouse, Brad,Welch, Mike,Topalov, George,Littman, Nicole,Callejo, Michele,Gloor, Susan,Martinson, Matthew,Laird, Ellen,Brandhuber, Barbara J.,Vigers, Guy,Morales, Tony,Woessner, Rich,Randolph, Nikole,Lyssikatos, Joseph,Olivero, Alan
scheme or table, p. 4692 - 4695 (2009/04/06)
Herein we describe a novel pyrazole-based class of ATP competitive B-Raf inhibitors. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. A subset of these inhibitors has demonstrated the ability to inhibit downstream ERK phosphorylation in LOX tumors from mouse xenograft studies.
