Semagacestat (LY450139)γ-secretase inhibitor CAS# 425386-60-3 |
- BMS-708163 (Avagacestat)
Catalog No.:BCC2104
CAS No.:1146699-66-2
- DAPT (GSI-IX)
Catalog No.:BCC3618
CAS No.:208255-80-5
- YO-01027 (Dibenzazepine, DBZ)
Catalog No.:BCC2100
CAS No.:209984-56-5
- Flurizan
Catalog No.:BCC2342
CAS No.:51543-40-9
- Begacestat
Catalog No.:BCC2346
CAS No.:769169-27-9
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 425386-60-3 | SDF | Download SDF |
| PubChem ID | 9843750 | Appearance | Powder |
| Formula | C19H27N3O4 | M.Wt | 361.44 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | LY-450139, LY 450139,Semagacestat | ||
| Solubility | DMSO : ≥ 100 mg/mL (276.67 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (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 | ||
| SMILES | CC(C)C(C(=O)NC(C)C(=O)NC1C2=CC=CC=C2CCN(C1=O)C)O | ||
| Standard InChIKey | PKXWXXPNHIWQHW-RCBQFDQVSA-N | ||
| Standard 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Semagacestat (LY450139) is an blocker of γ-secretase 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. | ||||||
| Targets | Aβ42 | Aβ40 | Aβ38 | Notch | |||
| IC50 | 10.9 nM | 12.1 nM | 12.0 nM | 14.1 nM | |||
| Cell experiment: | |
| Cell lines | H4 human glioma cells stably overexpressing human wild-type APP695 |
| Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
| Reacting condition | 24 h; 10 μM |
| Applications | Using H4 cells stably overexpressing human wild-type APP, LY450139 reduced the secretion of Aβ42, Aβ40, and Aβ38 in 96-well-cultured media and increased β-CTF in cell lysates as expected, although this increase was unexpectedly attenuated at high concentrations. The biphasic β-CTF response to LY450139 was also found in Western blot analysis of six-well-cultured cells using two anti-bodies, 82E1 and 6E10, which recognize the N-terminal region of Aβ. |
| Animal experiment: | |
| Animal models | Female Tg2576 mice |
| Dosage form | 3 mg/kg, oral taken. |
| Application | To determine the sites of β-CTF accumulation in response to LY450139, immunofluorescence of anti-human Aβ/β-CTF N-terminal-specific antibody (82E1) was applied to hippocampal slices from Tg2576 mice. Three-month-old Tg2576 mice were administered 3 mg/kg LY450139 for 8 d, with the brain fixed 3 h after the last administration. When immunofluorescence intensities in these regions were normalized with that in the CA3 stratum pyramidale of the same slice, LY450139-treated mice showed significantly higher relative immunoreactivity compared with the vehicle-treated mice. |
| Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| References: [1] Mitani Y, Yarimizu J, Saita K, et al. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice[J]. The Journal of Neuroscience, 2012, 32(6): 2037-2050. | |
Semagacestat (LY450139) Dilution Calculator
Semagacestat (LY450139) Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7667 mL | 13.8336 mL | 27.6671 mL | 55.3342 mL | 69.1678 mL |
| 5 mM | 0.5533 mL | 2.7667 mL | 5.5334 mL | 11.0668 mL | 13.8336 mL |
| 10 mM | 0.2767 mL | 1.3834 mL | 2.7667 mL | 5.5334 mL | 6.9168 mL |
| 50 mM | 0.0553 mL | 0.2767 mL | 0.5533 mL | 1.1067 mL | 1.3834 mL |
| 100 mM | 0.0277 mL | 0.1383 mL | 0.2767 mL | 0.5533 mL | 0.6917 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Semagacestat (also known as LY450139), [(2S)-2-hydroxy-N-((2S)-1-((1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1ylamino)-1-oxopropan-2-yl)-3-methylbutanamide] is an azepine class γ-secretase, which is currently being investigated as a potential disease-modifying agent for the treatment of Alzheimer’s disease (AD). It reduces the rate of formation of amyloid-β (Aβ), a major component of the neuritic plaque in the brains of AD patients, in human subjects and animal models including mice, beagle dogs and guinea pigs. According to previous studies, semagacestat slows the accumulation of Aβ in the brains of transgenic mice overexpressing mutant human amyloid precursor protein V717F (PDAPP mice) and exhibits a dose-dependent decrease of plasma in AD patients.
Reference
Ping Yi, Chad Hadden, Palaniappan Kulanthaivel, Nathan Calvert, William Annes, Thomas Brown, Robert J. Barbuch, Archana Chaudhary, Mosun A. Ayan-Oshodi, and Barbara J. Ring. Disposition and metabolism of semagacestat, a γ-secretase inhibitor, in humans. Drug Metabolism and Disposition 2010; 38(4): 554-565
- IPA-3
Catalog No.:BCC4978
CAS No.:42521-82-4
- 23-Hydroxylongispinogenin
Catalog No.:BCN7830
CAS No.:42483-24-9
- Isobutyl 4-Hydroxybenzoate
Catalog No.:BCN8412
CAS No.:4247-02-3
- Flunixin Meglumin
Catalog No.:BCC4429
CAS No.:42461-84-7
- H-ß-Ala-OEt.HCl
Catalog No.:BCC2852
CAS No.:4244-84-2
- Pinostilbene
Catalog No.:BCN5483
CAS No.:42438-89-1
- Pashanone
Catalog No.:BCN5482
CAS No.:42438-78-8
- 1-Benzylimidazole
Catalog No.:BCC8462
CAS No.:4238-71-5
- ML161
Catalog No.:BCC3642
CAS No.:423735-93-7
- Buxtamine
Catalog No.:BCC8135
CAS No.:4236-73-1
- (-)-Gallocatechin gallate
Catalog No.:BCN6328
CAS No.:4233-96-9
- SC 57461A
Catalog No.:BCC2348
CAS No.:423169-68-0
- Crocin
Catalog No.:BCN2373
CAS No.:42553-65-1
- Sotrastaurin (AEB071)
Catalog No.:BCC3857
CAS No.:425637-18-9
- 8-Hydroxy-5-O-beta-D-glucopyranosylpsoralen
Catalog No.:BCN1443
CAS No.:425680-98-4
- Luteolin-6-C-glucoside
Catalog No.:BCN4985
CAS No.:4261-42-1
- TAK-700 (Orteronel)
Catalog No.:BCC2280
CAS No.:426219-18-3
- TAK-700 salt
Catalog No.:BCC1979
CAS No.:426219-53-6
- 21,23-Dihydro-23-hydroxy-21-oxozapoterin
Catalog No.:BCN7230
CAS No.:426266-88-8
- Dehydrodiconiferyl alcohol
Catalog No.:BCN6878
CAS No.:4263-87-0
- Hemapolin
Catalog No.:BCC8994
CAS No.:4267-80-5
- 4-Hydroxy-3-methoxyphenyl O-beta-D-6-O-syringate-glucopyranoside
Catalog No.:BCN1442
CAS No.:426821-85-4
- NS 5806
Catalog No.:BCC7872
CAS No.:426834-69-7
- S-Isopropylisothiourea hydrobromide
Catalog No.:BCC6837
CAS No.:4269-97-0
Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease.[Pubmed:19527190]
Expert Opin Pharmacother. 2009 Jul;10(10):1657-64.
BACKGROUND: Alzheimer's disease is thought to be caused by increased formations of neurotoxic amyloid beta (A beta) peptides, which give rise to the hallmark amyloid plaques. Therefore, pharmacological agents that reduce A beta formation may be of therapeutic benefit. OBJECTIVE: This paper reviews the pharmacology and chemical efficacy of an A beta-lowering agent, Semagacestat (LY450139). METHODS: A review of the published literature pertaining to semagacestat was obtained using several electronic search engines; unpublished data on file at Eli Lilly and Co. were used as supplementary material. RESULTS/CONCLUSIONS: Semagacestat treatment lowers plasma, cerebrospinal fluid and brain A beta in a dose-dependent manner in animals and plasma and cerebrospinal fluid A beta in humans, compared with placebo-treated patients. On the basis of extant data, semagacestat seems to be well tolerated, with most adverse events related to its actions on inhibition of peripheral Notch cleavage. Thus far, clinical efficacy has not been detectable because of the short duration of the current trials. Phase III trials with 21 months of active treatment are currently underway.
ACS chemical neuroscience molecule spotlight on semagacestat (LY450139).[Pubmed:22778845]
ACS Chem Neurosci. 2010 Aug 18;1(8):533-4.
Semagacestat (LY450139) is a novel gamma-secretase inhibitor currently in late-stage development by Eli Lilly and Company as a potential treatment for Alzheimer's disease (AD). Semagacestat is currently being studied in two phase III clinical trials.
