Semagacestat

• CAT Number: I003524
• CAS Number: 425386-60-3
• Molecular Formula: C₁₉H₂₇N₃O₄
• Molecular Weight: 361.44
• Purity: ≥95%
• Synonyms: (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide
• Target: Amyloid β
• Solubility: DMSO ≥70mg/mL Water <1.2mg/mL Ethanol ≥41mg/mL
• Storage: 3 years -20℃ powder
• IC50: 10.9/12.1/12.0 nM (Aβ42/Aβ40/Aβ38); 14.1 nM (Notch signaling) [1]
• InChI: InChI=1S/C19H27N3O4/c1-11(2)16(23)18(25)20-12(3)17(24)21-15-14-8-6-5-7-13(14)9-10-22(4)19(15)26/h5-8,11-12,15-16,23H,9-10H2,1-4H3,(H,20,25)(H,21,24)/t12-,15-,16-/m0/s1
• InChIKey: PKXWXXPNHIWQHW-RCBQFDQVSA-N
• SMILES: CC(C)C(C(=O)NC(C)C(=O)NC1C2=CC=CC=C2CCN(C1=O)C)O

Semagacestat (LY450139) (Cat.No:I003524) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM.

Reference

1:Changes in Neuropsychiatric Inventory Associated with Semagacestat Treatment of Alzheimer/’s Disease. Rosenberg PB, Lanctôt KL, Herrmann N, Mintzer JE, Porsteinsson AP, Sun X, Raman R.J Alzheimers Dis. 2016 Aug 10;54(1):373-81. doi: 10.3233/JAD-151113. PMID: 27567808 2:A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans. Hölttä M, Dean RA, Siemers E, Mawuenyega KG, Sigurdson W, May PC, Holtzman DM, Portelius E, Zetterberg H, Bateman RJ, Blennow K, Gobom J.Alzheimers Res Ther. 2016 Mar 7;8(1):11. doi: 10.1186/s13195-016-0178-x. PMID: 26948580 Free PMC Article3:Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer/’s disease. Doody RS, Raman R, Sperling RA, Seimers E, Sethuraman G, Mohs R, Farlow M, Iwatsubo T, Vellas B, Sun X, Ernstrom K, Thomas RG, Aisen PS; Alzheimer’s Disease Cooperative Study..Alzheimers Res Ther. 2015 Jun 10;7(1):36. doi: 10.1186/s13195-015-0121-6. eCollection 2015. PMID: 26064192 Free PMC Article4:Neuropathological and biochemical assessments of an Alzheimer/’s disease patient treated with the γ-secretase inhibitor semagacestat. Roher AE, Maarouf CL, Kokjohn TA, Whiteside CM, Kalback WM, Serrano G, Belden C, Liebsack C, Jacobson SA, Sabbagh MN, Beach TG.Am J Neurodegener Dis. 2014 Dec 5;3(3):115-33. eCollection 2014. PMID: 25628963 Free PMC Article5:Safety profile of semagacestat, a gamma-secretase inhibitor: IDENTITY trial findings. Henley DB, Sundell KL, Sethuraman G, Dowsett SA, May PC.Curr Med Res Opin. 2014 Oct;30(10):2021-32. doi: 10.1185/03007995.2014.939167. Epub 2014 Jul 14. PMID: 24983746 6:Semagacestat for treatment of Alzheimer/’s disease. Pomara N.N Engl J Med. 2013 Oct 24;369(17):1661. doi: 10.1056/NEJMc1310845#SA2. No abstract available. PMID: 24152269 7:Semagacestat for treatment of Alzheimer/’s disease. Gupta VB, Gupta VK, Martins R.N Engl J Med. 2013 Oct 24;369(17):1660-1. doi: 10.1056/NEJMc1310845#SA1. No abstract available. PMID: 24152268 8:Semagacestat for treatment of Alzheimer/’s disease. Doody RS, Aisen PS, Iwatsubo T.N Engl J Med. 2013 Oct 24;369(17):1661. doi: 10.1056/NEJMc1310845. No abstract available. PMID: 24152267 Free Article9:A phase 3 trial of semagacestat for treatment of Alzheimer/’s disease. Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS; Alzheimer/’s Disease Cooperative Study Steering Committee., Siemers E, Sethuraman G, Mohs R; Semagacestat Study Group..N Engl J Med. 2013 Jul 25;369(4):341-50. doi: 10.1056/NEJMoa1210951. PMID: 23883379 Free Article10:Effects of the γ-secretase inhibitor semagacestat on hippocampal neuronal network oscillation. Hajós M, Morozova E, Siok C, Atchison K, Nolan CE, Riddell D, Kiss T, Hajós-Korcsok E.Front Pharmacol. 2013 Jun 14;4:72. doi: 10.3389/fphar.2013.00072. eCollection 2013. PMID: 23785331 Free PMC Article