(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide
Semagacestat
CAS: 425386-60-3
Molecular Formula: C19H27N3O4
(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide - Names and Identifiers
| Name | Semagacestat |
| Synonyms | LY450139 semagacestat Semagacestat Unii-3yn0602W4w LY450139(Semagacestat) (2S)-2-HYDROXY-3-METHYL-N-[(2S)-1-{[(1S)-3-METHYL-2-OXO-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-1-YL]AMINO}-1-OXOPROPAN-2-YL]BUTANAMIDE (2S)-2-Hydroxy-3-methyl-N-[(1S)-1-methyl-2-oxo-2-[[(1S)-2,3,4,5-tetrahydro-3-methyl-2-oxo-1H-3-benzazepin-1-yl]amino]ethyl]butanamide (2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide Butanamide, 2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-oxo-2-[[(1S)-2,3,4,5- tetrahydro-3-methyl-2-oxo-1H-3-benzazepin-1-yl]amino]ethyl]-, (2S)- |
| CAS | 425386-60-3 |
| EINECS | 1592732-453-0 |
| InChI | InChI=1/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 |
(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide - Physico-chemical Properties
| Molecular Formula | C19H27N3O4 |
| Molar Mass | 361.44 |
| Density | 1.22 |
| Melting Point | 208-212 °C |
| Boling Point | 681.9±55.0 °C(Predicted) |
| Flash Point | 366.2℃ |
| Solubility | ≥72 mg/mL in DMSO <1 mg/mL in DMSO ≥43 mg/mL in Ethanol |
| Vapor Presure | 0mmHg at 25°C |
| Appearance | Solid |
| Color | White |
| pKa | 12.97±0.20(Predicted) |
| Storage Condition | 2-8°C |
| Refractive Index | 1.576 |
| Use | A γ-secretase blocker of Aβ42, Aβ40 and Aβ38 |
| In vitro study | Semagacestat reduced the secretion of Aβ42, Aβ40 and Aβ38 from H4 human glioma cells stably over-expressing human wild-type into the culture medium with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, respectively, which did not affect cell viability. Semagacestat also increases β-CTF in Cell Lysates with an ECmax of 16.0 nM, and this increase can be rapidly reduced at the highest concentration. Semagacestat inhibits Notch signaling with an IC50 of 14.1 nM. Semagacestat reduced the secretion of Aβ40 from murine CTX expressing endogenous murine APP in a concentration-dependent manner, but the formation of Aβ42 in murine CTX was 12-fold lower than that of aβ40, consistent with the neural metadata of wild-type mice. |
| In vivo study | The APP transgenic Tg2576 mice of 5.5 months old were orally administered with Semagacestat at a dose of 1 mg/kg, which significantly improved the memory impairment, and disappeared after 8 days of sub-chronic dose administration. LY450139 acts at doses of 10 mg/kg and 30 mg/kg to reduce Aβ42 and Aβ40, and Aβ42 and Aβ40 are reduced by 22-23% and 36-41%, respectively, and the dose of 0.3-10 mg/kg treatment to increase beta-CTF, this effect is dose-dependent, does not inhibit other brain gamma-secreting substrates, such as Notch, N-cadherin or epha4, but normal cognition in wild-type mice in the Y-maze impairment trial, and 3-month-old Tg2576 mice failed to repair cognitive deficits. |
(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide - Risk and Safety
| HS Code | 29337900 |
(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide - Introduction
Semagacestat (LY450139) is a γ-secretase inhibitor. When acting on Aβ42, Aβ40 and Aβ38, IC50 is 10.9 nM, 12.1 nM and 12.0 nM respectively, and also inhibits Notch signaling pathway, IC50 is 14.1 nM.
Last Update：2022-10-16 17:25:11
(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide - Reference Information
| biological activity | Semagacestat (LY450139) is a γ-secretase inhibitor that acts on Aβ42,Aβ40 and Aβ38,IC50 is 10.9 nM,12.1 nM and 12.0 nM respectively, and also inhibits Notch signaling pathway. IC50 in human glioma cells is 14.1 nM. Phase 3. |
| target | TargetValue gamma secretase(Aβ42) (H4 human glioma cells) 10.9 nM gamma secretase(Aβ38) (H4 human glioma cells) 12.0 nM gamma secretase(Aβ40) (H4 human glioma cells) 12.1 nM Notch (H4 human glioma cells) 14.1 nM |
| Target | Value |
| γ secretase(Aβ42) (H4 human glioma cells) | 10.9 nM |
| γ secretase(Aβ38) (H4 human glioma cells) | 12.0 nM |
| γ secretase(Aβ40) (H4 human glioma cells) | 12.1 nM |
| Notch (H4 human glioma cells) | 14.1 nM |
| in vitro study | Semagacestat reduce the secretion of Aβ42, Aβ40 and Aβ38 into the culture medium by H4 human glioma cells stably overexpressing human wild type, with IC50 of 10.9 nM, 12.1 nM and 12.0 nM respectively, which will not affect cell activity. Semagacestat also increases β-CTF in cytolyss, ECmax is 16.0 nM, and this increase can be rapidly reduced at the highest concentration. Semagacestat suppress Notch signal, IC50 is 14.1 nM. Semagacestat decreased the secretion of Aβ40 into the medium by murine CTX expressing endogenous murine APP, this effect was concentration dependent, but the formation of Aβ42 in murine CTX was 12 times lower than that of Aβ40, consistent with the neural metadata of wild-type mice. |
| in vivo study | Semagacestat 5.5-month-old APP transgenic Tg2576 mice were orally administered at a dose of 1 mg/kg, which significantly improved memory impairment and disappeared after 8 days of subchronic dose administration. LY450139 the dose of 10 mg/kg and 30 mg/kg is applied to reduce Aβ42 and Aβ40 respectively, Aβ42 and Aβ40 are reduced by 22-23% and 36-41% respectively, and the dose of 0.3-10 mg/kg is used to increase β-CTF. This effect is dose-dependent and will not inhibit other brain γ-secreting substrates, such as Notch, N-cadherin or EphA4, however, the normal cognition of wild-type mice and the 3-month-old Tg2576 mice in the Y-maze impairment test could not repair the cognitive defect. |
Last Update：2024-04-09 21:04:16
![(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-{[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-2-oxoethyl]butanamide](http://res.chembk.com/assets/images/structure/307086.gif)
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Product Name: Semagacestat (LY450139) Visit Supplier Webpage Request for quotationCAS: 425386-60-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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