WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 522690
CAS#: 870843-42-8
Description: E2012 is a γ-secretase modulator (GSM). E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. E2012 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.
MedKoo Cat#: 522690
Name: E2012
CAS#: 870843-42-8
Chemical Formula: C25H26FN3O2
Exact Mass: 419.2009
Molecular Weight: 419.5004
Elemental Analysis: C, 71.58; H, 6.25; F, 4.53; N, 10.02; O, 7.63
Synonym: E2012; E-2012; E 2012.
IUPAC/Chemical Name: (S,E)-1-(1-(4-fluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one
InChi Key: PUOAETJYKQITMO-LANLRWRYSA-N
InChi Code: InChI=1S/C25H26FN3O2/c1-17-15-28(16-27-17)23-11-6-19(14-24(23)31-3)13-21-5-4-12-29(25(21)30)18(2)20-7-9-22(26)10-8-20/h6-11,13-16,18H,4-5,12H2,1-3H3/b21-13+/t18-/m0/s1
SMILES Code: O=C1N([C@H](C2=CC=C(F)C=C2)C)CCC/C1=C\C3=CC=C(N4C=C(C)N=C4)C(OC)=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 419.5004 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Sjödin S, Andersson KK, Mercken M, Zetterberg H, Borghys H, Blennow K, Portelius E. APLP1 as a cerebrospinal fluid biomarker for γ-secretase modulator treatment. Alzheimers Res Ther. 2015 Dec 22;7(1):77. doi: 10.1186/s13195-015-0160-z. PubMed PMID: 26689589; PubMed Central PMCID: PMC4687145.
2: Yesuvadian R, Krishnamoorthy J, Ramamoorthy A, Bhunia A. Potent γ-secretase inhibitors/modulators interact with amyloid-β fibrils but do not inhibit fibrillation: a high-resolution NMR study. Biochem Biophys Res Commun. 2014 May 16;447(4):590-5. doi: 10.1016/j.bbrc.2014.04.041. Epub 2014 Apr 18. PubMed PMID: 24747079.
3: Nakano-Ito K, Fujikawa Y, Hihara T, Shinjo H, Kotani S, Suganuma A, Aoki T, Tsukidate K. E2012-induced cataract and its predictive biomarkers. Toxicol Sci. 2014 Jan;137(1):249-58. doi: 10.1093/toxsci/kft224. Epub 2013 Oct 1. PubMed PMID: 24085193.
4: Pozdnyakov N, Murrey HE, Crump CJ, Pettersson M, Ballard TE, Am Ende CW, Ahn K, Li YM, Bales KR, Johnson DS. γ-Secretase modulator (GSM) photoaffinity probes reveal distinct allosteric binding sites on presenilin. J Biol Chem. 2013 Apr 5;288(14):9710-20. doi: 10.1074/jbc.M112.398602. Epub 2013 Feb 8. PubMed PMID: 23396974; PubMed Central PMCID: PMC3617273.
5: Borgegard T, Juréus A, Olsson F, Rosqvist S, Sabirsh A, Rotticci D, Paulsen K, Klintenberg R, Yan H, Waldman M, Stromberg K, Nord J, Johansson J, Regner A, Parpal S, Malinowsky D, Radesater AC, Li T, Singh R, Eriksson H, Lundkvist J. First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms. J Biol Chem. 2012 Apr 6;287(15):11810-9. doi: 10.1074/jbc.M111.305227. Epub 2012 Feb 13. PubMed PMID: 22334705; PubMed Central PMCID: PMC3320929.
6: Portelius E, Gustavsson MK, Zetterberg H, Andreasson U, Blennow K. Evaluation of the performance of novel Aβ isoforms as theragnostic markers in Alzheimer's disease: from the cell to the patient. Neurodegener Dis. 2012;10(1-4):138-40. doi: 10.1159/000334537. Epub 2012 Feb 1. Review. PubMed PMID: 22302034.
7: 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. doi: 10.3233/JAD-2010-100573. PubMed PMID: 20634579.
