CCT020312

CCT020312 is a selective EIF2AK3/PERK activator. CCT020312 elicits EIF2A phosphorylation in cells. IC50 & Target: EIF2AK3/PERK^[1][2]. In Vitro: Treatment of HT29 cells with CCT020312 for 24 hours reveals a concentration-dependent loss of P-S608-pRB signal, with a linear response between 1.8 and 6.1 μM^[1].
CCT020312 treatment effectively inhibits cell proliferation (as measured at 96 hours) even if treatment is for 2 hours only with subsequent compound washout, indicating that CCT020312 is capable of eliciting durable rather than transient cytostasis^[1].
Treatment of HT29 cells with 10 μM CCT020312 for 24 hours reduces the amount of the G1/S cyclins D1, D2, E and A as well as the CDK catalytic subunit CDK2 and increased the level of the CDK inhibitor p27KIP1 present in such cells^[1]. In Vivo: Treatment of 15-week-old wildtype mice with the PERK activator CCT020312 (1-5 mg/kg; i.p.; once daily for 3 days) leads to increased levels of phosphorylated PERK and NRF2 in brain homogenates^[2].
P301S transgenic mice treated with CCT020312 (2 mg/kg; i.p.; once daily for 6 weeks) performes significantly better in Morris water maze^[2].