EPIC-0628 is an inhibitor of the HOTAIR-EZH2 interaction and promotes ATF3 expression. The long noncoding RNA HOTAIR has been found to regulate glioblastoma (GBM) progression and mediate DNA damage repair (DDR) by interacting with the catalytic subunit EZH2 of PRC2. EPIC-0628 also inhibits the ATF3-p38-E2F1 DDR pathway to inhibit the HR pathway and upregulates CDKN1A (p21) expression, causing cell cycle arrest. EPIC-0628 also synergizes with Temozolomide (TMZ) to enhance its in vivo potency.
EPIC-0628 (20 μM; 48 h) arrests the U87 cell cycle in the G1 phase[1].
References:
[1]. Yang E, et al. EPIC-0628 abrogates HOTAIR/EZH2 interaction and enhances the temozolomide efficacy via promoting ATF3 expression and inhibiting DNA damage repair in glioblastoma. Cancer Lett. 2024 Apr 28;588:216812.