Product Name :
GDC-0879
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.
CAS:
905281-76-7
Molecular Weight:
334.37
Formula:
C19H18N4O2
Chemical Name:
(E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2, 3-dihydro-1H-inden-1-one oxime
Smiles :
O/N=C1\CCC2=CC(=CC=C2\1)C1=CN(CCO)N=C1C1C=CN=CC=1
InChiKey:
DEZZLWQELQORIU-RELWKKBWSA-N
InChi :
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+
Purity:
≥98% (or refer to the Certificate of Analysis)
Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition :
Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.{{Protease Inhibitor Cocktail} web|{Protease Inhibitor Cocktail} Immunology/Inflammation|{Protease Inhibitor Cocktail} Biological Activity|{Protease Inhibitor Cocktail} In Vivo|{Protease Inhibitor Cocktail} manufacturer}
Shelf Life:
≥12 months if stored properly.
Stock Solution Storage:
0 – 4 oC for 1 month or refer to the Certificate of Analysis.
Additional information:
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.|Product information|CAS Number: 905281-76-7|Molecular Weight: 334.37|Formula: C19H18N4O2|Synonym:|GDC0879|GDC 0879|Chemical Name: (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2, 3-dihydro-1H-inden-1-one oxime|Smiles: O/N=C1\CCC2=CC(=CC=C2\1)C1=CN(CCO)N=C1C1C=CN=CC=1|InChiKey: DEZZLWQELQORIU-RELWKKBWSA-N|InChi: 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+|Technical Data|Appearance: Solid Power|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO: 66 mg/mLwarmed(197.{{LM10} web|{LM10} Protocol|{LM10} Description|{LM10} custom synthesis|{LM10} Autophagy} 38 mM). Water: Insoluble.|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.PMID:23439434 |Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined|HS Tariff Code: 382200|How to use|In Vitro:|GDC-0879 also inhibits cellular pERK with IC50 of 63 nM. GDC-0879 shows comparable potency in A375 melanoma and Colo205 colorectal carcinoma cell lines, both of which are B-RafV600E mutant, with IC50 of 59 nM and 29 nM for pMEK1 inhibition respectively. GDC-0879 potently inhibits B-RafV600E in Malme3M cells with IC50 of 0.75 μM. GDC-0879 also shows EC50 values In Vivo:|In GDC-0879 treated mice, both cell line- and patient-derived BRAFV600E tumors exhibit stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared to mutant KRAS-expressing tumors. Although there is involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression is observed for some KRAS-mutant tumors following GDC-0879 administration. Whereas GDC-0879-mediated efficacy is associated strictly with B-RafV600E status, MEK inhibition also attenuates proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of B-RafV600E melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of PI3K pathway activity.|References:|Hoeflich KP, et al. Cancer Res. 2009, 69(7), 3042-3051.Wong H, et al. J Pharmacol Exp Ther. 2009, 329(1), 360-367.Products are for research use only. Not for human use.|
