SML1953

GDC-0879

≥98% (HPLC)

• Synonym(s): 1H-Inden-1-one, 2,3-dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-, oxime, 2,3-Dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-1H-inden-1-one oxime, 2-[4-[(1E)-1-(Hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol, 5-(1-(2-Hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime, AR00341677, GDC0879
• Empirical Formula (Hill Notation): C₁₉H₁₈N₄O₂
• CAS Number: 905281-76-7
• Molecular Weight: 334.37
• UNSPSC Code: 12352200
• NACRES: NA.77
• MDL number: MFCD16875916
• Assay: ≥98% (HPLC)
• Form: powder

Properties

• Quality Segment: 100
• assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear (warmed)
• storage temp.: 2-8°C
• SMILES string: OCCN(N=C1C2=CC=NC=C2)C=C1C3=CC=C4C(CC/C4=N\O)=C3
• 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+
• InChI key: DEZZLWQELQORIU-RELWKKBWSA-N

Description

Biochem/physiol Actions

GDC-0879 (AR00341677) is an orally active, ATP site-targeting, highly potent Raf inhibitor (IC50 against V600E B-Raf-catalyzed MEK phophorylation = 0.13 nM with 4 μM ATP; IC50 against pERK in V600E B-Raf-expressing cells = 29 nM/Colo205, 59 nM/A375, 63 nM/Malme-3M) with great selectivity over >200 protein kinases (IC50 >1 μM). Oral administration is shown to effectively suppress Colo205 and A375 xenografts-derived tumor growth and pMEK1 in mice in vivo (35 mg/kg bid; 50-200 mg/kg qd or bid). Paradoxically, GDC-0879 also induces wild-type and enhances V600E B-Raf dimerization in an allosteric manner independent of kinase activity inhibition, resulting in selective anti-proliferation activity against V600E B-Raf cancer cells, but not in KRAS mutant or RAS/WT Raf cells, where GDC-0879 induces formation of B–C and A–B heterodimers and downstream signaling activation.

Orally active potent Raf inhibitor with V600E B-Raf-selective anticancer activity, while enhancing Raf signaling in KRAS mutant or RAS/WT Raf cells.

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable