| Bioactivity | E 2012 is a potent gamma (γ) secretase modulator without affecting Notch processing. E 2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. E 2012 aims at Alzheimer's disease by reduction of amyloid β-42, and induces cataract following repeated doses in the rat[1]. | ||||||||||||
| Invitro | E2012 has concentration-dependent inhibitory effects on cholesterol biosynthesis in primary culture of rat hepatocytes and HepG2 cells with IC50s of 11.0, and 15.1 nM, respectively[1]. | ||||||||||||
| In Vivo | In vivo lenticular concentration of E 2012 after 13-week repeated dose with cataract was well above those where inhibition is observed in vitro. E 2012 induces cataract in the rat by inhibiting DHCR24 at the final step of cholesterol synthesis with associated elevation in desmosterol within the lens, preceded by desmosterol changes that would serve as a predictive safety biomarker for lenticular opacity[2]. | ||||||||||||
| Name | E 2012 | ||||||||||||
| CAS | 870843-42-8 | ||||||||||||
| Formula | C25H26FN3O2 | ||||||||||||
| Molar Mass | 419.49 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Nakano-Ito K, et al. E2012-induced cataract and its predictive biomarkers. Toxicol Sci. 2014 Jan;137(1):249-58. [2]. Portelius E, Van Broeck B, Andreasson U, Gustavsson MK, Mercken M, Zetterberg H, Borghys H, Blennow K.Acute effect on the Aβ isoform pattern in CSF in response to γ-secretase modulator and inhibitor treatment in dogs.J Alzheimers Dis. 2010;21(3):1005-12. |