GNE-272

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效且选择性的 CBP/EP300 溴结构域抑制剂，对 CBP 和 EP300 的 IC50 分别为 0.02 和 0.03 uM。

A potent and selective the bromodomains of CBP/EP300 inhibitor with IC50 of 0.02 and 0.03 uM for CBP and EP300, respectively; displays high selectivity over BRD4 (1) and other BRDs (>10 uM); shows antiproliferative effect in hematologic cancer cell lines and modulates MYC expression in vivo; exhibits excellent in vivo PK and antitumor activity in an AML tumor model.

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.

GNE 272 | GNE272

Chromatin/Epigenetic

Bromodomain

Bromodomain

Cancer

——

1936428-93-1

424.48

C22H25FN6O2

>98% (HPLC)

DMSO : ≥ 150 mg/mL 353.38 mM

CC(N1CCC2=C(C(NC3=C(F)C=C(C4=CN(C)N=C4)C=C3)=NN2[C@H]5CCOC5)C1)=O

(S)-1-(3-((2-Fluoro-4-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-1-(tetrahydrofuran-3-yl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-5(4H)-yl)ethanone

(-20℃)

With Ice Pack

≥ 2 years