Uses
CCT020312 is a selective EIF2AK3/PERK activator. CCT020312 elicits EIF2A phosphorylation in cells.
Biological Activity
CCT020312 is a selective activator of EIF2AK3/PERK. It induces phosphorylation of EIF2A in cells.
in vitro
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.
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: | 9-week-old P301S tau transgenic mice[2] |
| Dosage: | 2 mg/kg |
| Administration: | Intraperitoneal injection; once daily for 6 weeks |
| Result: | P301S transgenic mice treated with CCT020312 performed significantly better in Morris water maze.
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References
[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. DOI:
10.1371/journal.pone.0028568[2] Bruch J, et al. PERK activation mitigates tau pathology in vitro and in vivo. EMBO Mol Med. 2017 Mar;9(3):371-384. DOI:
10.15252/emmm.201606664
