EOAI3402143

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

EOAI3402143（去泛素酶抑制剂 G9，EOAI 3402143）是一种新型共价去泛素酶 Usp9x/Usp24 抑制剂。

EOAI3402143 (Deubiquitinase inhibitor G9, EOAI 3402143) is a novel covalent deubiquitinase Usp9x/Usp24 inhibitor with increased aqueous solubility and greater cellular Usp9x inhibitory activity than WP1130; displays nM apoptotic activity against other myeloma cell lines and diffuse large B-cell lymphomas cells; increases tumor cell apoptosis, and fully blocks or regresses myeloma tumors in mice; also inhibis Usp5.

EOAI3402143 retains potent Usp9x and Usp5 inhibitory activity. EOAI3402143 dose-dependently inhibits Usp9x and Usp24 activity, increases tumor cell apoptosis. Treatment of UM-2, UM-6, UM-16, and UM-76 with Usp9x inhibitor EOAI3402143 (G9) dose-dependently suppresses cell survival, while 600 nM of EOAI3402143 completely suppresses UM-2 3D colony growth when compared to untreated vehicle controls.

To examine this potential, the effect of EOAI3402143 (G9) treatment is investigated on human MIAPACA2 tumor xenografts. Human MIAPACA2 cells are injected subcutaneously into NSG mice. Primary tumor development is monitored by caliper measurements, and once measurable, mice are separated into two groups and are treated with either vehicle control (PEG300/DMSO) or G9 at 15 mg/kg. Tumor growth, animal weight, behavior, and mobility are monitored during treatment. In parallel, murine 8041 tumors are also established and subjected to similar G9 treatment and tumor monitoring regimen as the human MIAPACA2 xenografts. Consistent with the in vitro findings, Usp9x inhibition results in the suppression of tumor growth in human tumor xenografts, but any significant effect on the growth of 8041 tumors xenografts is not observed, although the Usp9x activity is inhibited effectively by EOAI3402143 treatment in both human MIAPACA2 and mouse 8041 xenograft tumors.

Deubiquitinase inhibitor G9 | EOAI 3402143

Proteasome/Ubiquitin

DUB

DUB

——

——

1699750-95-2

503.424

C25H28Cl2N4O3

>98% (HPLC)

DMSO : 50 mg/mL 99.32 mM; H2O : < 0.1 mg/mL

CCCC(C1=CC=C(C=C1)OCCN2CCOCC2)NC(=O)C(=CC3=C(C=CC(=N3)Cl)Cl)C#N

(E)-2-cyano-3-(3,6-dichloropyridin-2-yl)-N-(1-(4-(2-morpholinoethoxy)phenyl)butyl)acrylamide

(-20℃)

With Ice Pack

≥ 2 years