SML2111

GSK8814

≥98% (HPLC)

• Synonym(s): 8-((3R,4R,5S)-3-((4,4-Difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-ylamino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one, 8-[[(3R,4R,5S)-3-[(4,4-Difluorocyclohexyl)methoxy]-5-methoxy-4-piperidinyl]amino]-3-methyl-5-(5-methyl-3-pyridinyl)-1,7-naphthyridin-2(1H)-one
• Empirical Formula (Hill Notation): C₂₈H₃₅F₂N₅O₃
• CAS Number: 1997369-78-4
• Molecular Weight: 527.61
• UNSPSC Code: 12352200

Properties

• assay: ≥98% (HPLC)
• form: powder
• color: colorless to very dark brown
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: −20°C
• SMILES string: O=C(N1)C(C)=CC2=C1C(N[C@H]3[C@H](OCC4CCC(F)(F)CC4)CNC[C@@H]3OC)=NC=C2C5=CN=CC(C)=C5

Description

Biochem/physiol Actions

GSK8814 is an aqueous soluble (>439 μM) inhibitor that targets ATAD2 & ATAD2B bromodomain (BD) with submicromolar affinity (pK_d = 8.1 for ATAD2 by ITC) and high selectivity (pIC₅₀ = 7.3/ATAD2 BD & 7.7/ATAD2B BD in competitive ligand binding assays by TR-FRET; pIC₅₀ ≤4.5 when using BD1/BD2 of BRD2-4 or BRDT). When tested using intact cells, GSK8814 effectively disrupts histone H3.3 interaction with ATAD2 BD construct (IC₅₀ = 2.7 μM), but not full-length ATAD2. GSK8814, but not its less active diastereomer GSK8815, is shown to suppress LNCaP colony formation in a soft agar assay, albeit with a high effective concentration (by 56% at 20 μM).

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3