GDC-0879

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

MedKoo CAT#: 401470

CAS#: 905281-76-7

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.


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10mg
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1g
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25mg
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2g
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50mg
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500mg
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5g
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GDC-0879, purity > 98%, is available through custom synthesis. Minimum 1 gram order is requested. Current shipping out time is about 70 days after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 401470
Name: GDC-0879
CAS#: 905281-76-7
Chemical Formula: C19H18N4O2
Exact Mass: 334.14298
Molecular Weight: 334.37182
Elemental 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

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


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 the kinase ARAF promotes MAPK pathway activation and cell migration. Sci Signal. 2014 Aug 5;7(337):ra73. doi: 10.1126/scisignal.2005484. PubMed PMID: 25097033.

2: Doma E, Rupp C, Varga A, Kern F, Riegler B, Baccarini M. Skin tumorigenesis stimulated by Raf inhibitors relies upon Raf functions that are dependent and independent of ERK. Cancer Res. 2013 Dec 1;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, Xavier RJ, Engelman JA, Martin ES, Hung KE. Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer. 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 Cancer Res. 2013 Jul 15;19(14):4018. PubMed PMID: 23549875; PubMed Central PMCID: PMC3815598.

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

5: Chou B, Adler RS, Meng M, Percey S, Dean B, Hop CE, Shin YG. Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0879 and its metabolite in dog plasma using solid phase extraction. J Pharm Biomed Anal. 2012 Nov;70:354-61. doi: 10.1016/j.jpba.2012.05.029. Epub 2012 Jun 1. 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 the scaffolding function of kinase suppressor of Ras, CRAF and BRAF. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6067-72. doi: 10.1073/pnas.1102554108. Epub 2011 Mar 25. PubMed PMID: 21441104; PubMed Central PMCID: PMC3076888.

7: Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, 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 the MAPK 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, Shin Y, Wong S, Ran Y. Disposition of GDC-0879, a B-RAF kinase inhibitor in preclinical 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, 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. 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-pyraz ol-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. doi: 10.1124/jpet.108.148189. Epub 2009 Jan 15. PubMed PMID: 19147858.