GNE-272 is a in Vivo Probe for the Bromodomains of CBP/EP300.

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

GNE272,GNE 272

Powder

DMSO : ≥ 150 mg/mL (353.38 mM)

Histone Acetyltransferase

GNE-272 is exquisitely selective for CBP/ EP300 and remarkably selective (650-fold) over BRD4. When tested at 10 μM in 35 kinase panel and 42 receptors off-target screening panel, GNE-272 does not inhibit any target at >30%. In addition, GNE-272 does not inhibit (>10 μM, top concentration) several cytochrome P450s (3A4, 1A2, 2C9, 2C19, 2D6). The compound has good potency in the BRET cellular assay. In an orthogonal measure of the target engagement, GNE-272 is shown to inhibit the expression of MYC10 (MV4−11 cell line) with an EC50 of 0.91 μM and good correlation between the BRET and MYC cellular assays is observed.

GNE-272 demonstrates low clearance following a 1 mg/ kg intravenous dose in a mouse PK experiment and good oral bioavailability when dosed at 100 mg/kg, reaching an unbound Cmax of 26 μM. GNE-272 shows a marked antiproliferative effect in hematologic cancer cell lines and modulates MYC expression in vivo that corresponds with antitumor activity in an AML tumor model.