GDC-0879

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WARNING: This product is for research use only, not for human or veterinary use.

Description:GDC-0879 is a highly selective, potent, and orally bioavailable RAF small-molecule inhibitor. In GDC-0879 -treated mice, both cell line- and patient-derived BRAF(V600E) tumors exhibited stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared with mutant KRAS-expressing tumors.

Price and Availability

GDC-0879, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 401470Name: GDC-0879CAS#: 905281-76-7Chemical Formula: C19H18N4O2Exact Mass: 334.14298Molecular Weight: 334.37182Elemental Analysis:C, 68.25; H, 5.43; N, 16.76; O, 9.57

Synonym:GDC0879; GDC-0879; GDC 0879.

IUPAC/Chemical Name:(E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime

InChi Key:DEZZLWQELQORIU-RELWKKBWSA-N

InChi Code:InChI=1S/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+

SMILES Code:OCCN1N=C(C2=CC=NC=C2)C(C3=CC4=C(/C(CC4)=N/O)C=C3)=C1

Technical Data

Additional Information

 GDC-0879 is a highly selective, novel potent, orally bioavailable B-Raf inhibitor in various in vitro and cell-based assays with an IC50 estimate of 0.13 nM against purified B-Raf V600E enzyme and a cellular pERK IC50 of 63 nM in the MALME-3M cell line GDC-0879 is a highly selective, novel potent, orally bioavailable B-Raf inhibitor in various in vitro and cell-based assays with an IC50 estimate of 0.13 nM against purified B-Raf V600E enzyme and a cellular pERK IC50 of 63 nM in the MALME-3M cell line

References

1: Mooz J, Oberoi-Khanuja TK, Harms GS, Wang W,Jaiswal BS, Seshagiri S, Tikkanen R, Rajalingam K. Dimerization of thekinase ARAF promotes MAPK pathway activation and cell migration. SciSignal. 2014 Aug 5;7(337):ra73. doi: 10.1126/scisignal.2005484. PubMedPMID: 25097033.

2: Doma E, Rupp C, Varga A, Kern F, Riegler B, Baccarini M. Skintumorigenesis stimulated by Raf inhibitors relies upon Raf functionsthat are dependent and independent of ERK. Cancer Res. 2013 Dec1;73(23):6926-37. doi: 10.1158/0008-5472.CAN-13-0748. Epub 2013 Oct 15.PubMed PMID: 24129679.

3: Coffee EM, Faber AC, Roper J, Sinnamon MJ, Goel G, Keung L, Wang WV,Vecchione L, de Vriendt V, Weinstein BJ, Bronson RT, Tejpar S, XavierRJ, Engelman JA, Martin ES, Hung KE. Concomitant BRAF and PI3K/mTORblockade is required for effective treatment of BRAF(V600E) colorectalcancer. Clin Cancer Res. 2013 May 15;19(10):2688-98. doi:10.1158/1078-0432.CCR-12-2556. Epub 2013 Apr 2. Erratum in: Clin CancerRes. 2013 Jul 15;19(14):4018. PubMed PMID: 23549875; PubMed CentralPMCID: PMC3815598.

4: Fuchs O. Targeting of NF-kappaB signaling pathway, other signalingpathways and epigenetics in therapy of multiple myeloma. CardiovascHematol Disord Drug Targets. 2013 Mar 1;13(1):16-34. Review. PubMedPMID: 23534949.

5: Chou B, Adler RS, Meng M, Percey S, Dean B, Hop CE, Shin YG.Validation and application of a liquid chromatography-tandem massspectrometric method for the determination of GDC-0879 and itsmetabolite in dog plasma using solid phase extraction. J Pharm BiomedAnal. 2012 Nov;70:354-61. doi: 10.1016/j.jpba.2012.05.029. Epub 2012 Jun1. PubMed PMID: 22717139.

6: Hu J, Yu H, Kornev AP, Zhao J, Filbert EL, Taylor SS, Shaw AS.Mutation that blocks ATP binding creates a pseudokinase stabilizing thescaffolding function of kinase suppressor of Ras, CRAF and BRAF. ProcNatl Acad Sci U S A. 2011 Apr 12;108(15):6067-72. doi:10.1073/pnas.1102554108. Epub 2011 Mar 25. PubMed PMID: 21441104; PubMedCentral PMCID: PMC3076888.

7: Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, AlvaradoR, Ludlam MJ, Stokoe D, Gloor SL, Vigers G, Morales T, Aliagas I, Liu B,Sideris S, Hoeflich KP, Jaiswal BS, Seshagiri S, Koeppen H, Belvin M,Friedman LS, Malek S. RAF inhibitors prime wild-type RAF to activate theMAPK pathway and enhance growth. Nature. 2010 Mar 18;464(7287):431-5.doi: 10.1038/nature08833. Epub 2010 Feb 3. PubMed PMID: 20130576.

8: Choo EF, Driscoll JP, Feng J, Liederer B, Plise E, Randolph N, ShinY, Wong S, Ran Y. Disposition of GDC-0879, a B-RAF kinase inhibitor inpreclinical species. Xenobiotica. 2009 Sep;39(9):700-9. doi:10.1080/00498250902991827. PubMed PMID: 19552528.

9: 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, FriedmanLS, Belvin M. Antitumor efficacy of the novel RAF inhibitor GDC-0879 ispredicted by BRAFV600E mutational status and sustained extracellularsignal-regulated kinase/mitogen-activated protein kinase pathwaysuppression. Cancer Res. 2009 Apr 1;69(7):3042-51. doi:10.1158/0008-5472.CAN-08-3563. Epub 2009 Mar 10. PubMed PMID: 19276360.

10: 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 kinaseinhibitor: understanding relationships between systemic concentrations,phosphorylated mitogen-activated protein kinase kinase 1 inhibition, andefficacy. J Pharmacol Exp Ther. 2009 Apr;329(1):360-7. doi:10.1124/jpet.108.148189. Epub 2009 Jan 15. PubMed PMID: 19147858.