| Bioactivity | CCT020312 is a selective EIF2AK3/PERK activator. CCT020312 elicits EIF2A phosphorylation in cells. | |||||||||
| Target | EIF2AK3/PERK. | |||||||||
| Invitro | 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]. Animal Model: | |||||||||
| Name | CCT020312 | |||||||||
| CAS | 324759-76-4 | |||||||||
| Formula | C31H30Br2N4O2 | |||||||||
| Molar Mass | 650.40 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [1]. Stockwell SR, et al.Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling. PLoS One. 2012;7(1):e28568. [2]. Bruch J, et al. PERK activation mitigates tau pathology in vitro and in vivo. EMBO Mol Med. 2017 Mar;9(3):371-384. |