BMS-708163 (Avagacestat) (Synonyms: BMS-708163) |
| رقم الكتالوجGC13673 |
A potent inhibitor of γ-secretase
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1146699-66-2
Sample solution is provided at 25 µL, 10mM.
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BMS-708163 is a potent selective and orally bioavailable inhibitor of γ-secretase with IC50 value of 0.3nM [1].
The cleavage of amyloid precusor protein APP by γ-secretase causes the production of Aβ40 and Aβ42, which are cytotoxic and cause AD. In vitro assay shows BMS-708163 inhibits the formation of Aβ40 and Aβ42 in H4-8Sw cells. It also inhibits the human recombinant CYPs in vitro with IC50 value of 20μM. Notch receptor is another substrate of γ-secretase. The inhibition of Notch signal pathway results in some side effects. It is shown that the activity of BMS-708163 to inhibit Notch is 190-fold weaker than to APP. In female rats, oral administration of BMS-708163 significantly reduces the production of Aβ in plasma and brain at 10mg/kg and 100mg/kg. In addition, BMS-708163 also reduces Aβ in brain and CSF in male beagle dogs [1].
References:
[1] Gillman KW, Starrett JE Jr, Parker MF, Xie K, Bronson JJ, Marcin LR, McElhone KE, Bergstrom CP, Mate RA, Williams R, Meredith JE Jr, Burton CR, Barten DM, Toyn JH, Roberts SB, Lentz KA, Houston JG, Zaczek R, Albright CF, Decicco CP, Macor JE, Olson RE. Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor. ACS Med Chem Lett. 2010 Mar 22;1(3):120-4.
Cell experiment: | The cell viability is assessed using a tetrazolium salt (WST-8)-based colorimetric assay from the Cell Counting Kit 8 (CCK-8). The cells are seeded into 96-well plates at an initial density of 5×103 cells/well and cultured for 24 h, after which the cells are cultured with DMSO, increased concentrations of gefitinib or Avagacestat (BMS-708163) , BIBW2992, or the combination of Avagacestat (BMS-708163) and BIBW2992 for an additional 48 h. The A450 is measured in a microplate reader after 10 µL of CCK-8 solution is added and incubated for 1 h. The percentage of growth is shown relative to untreated controls. |
Animal experiment: | Four- to six-week-old female Balb/c athymic (nu + /nu +) mice are anesthetized with ether. The mice are acclimatized for one week before being injected with 1.5×106 PC9/AB2 cells that have been resuspended in 200 μL of matrigel. When established tumors of approximately 150-300 mm3 in diameter are detected, the mice are randomly divided into groups and fed orally by gavage with either vehicle (1% methylcellulose, 0.2% Tween 80 in sterilized water), gefitinib (3 mg/kg diluted in vehicle), Avagacestat (BMS-708163) (10 mg/kg diluted in vehicle), or a combination of gefitinib (3 mg/kg) and Avagacestat (BMS-708163) (10 mg/kg) for 5 days/week. Each treatment group consists of eight mice. The tumor volume are measured and calculated every five days using the following formula: π/6×(larger diameter)×(smaller diameter)2. After 30 days, mice are killed by cervical dislocation. |
References: [1]. Gillman KW, et al. Letter Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable γ-Secretase Inhibitor. Med Chem Lett, 2010, 1 (3), 120-124. | |
| Cas No. | 1146699-66-2 | SDF | |
| المرادفات | BMS-708163 | ||
| Chemical Name | (2R)-2-[(4-chlorophenyl)sulfonyl-[[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoropentanamide | ||
| Canonical SMILES | C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl | ||
| Formula | C20H17ClF4N4O4S | M.Wt | 520.88 |
| الذوبان | ≥ 177.6 mg/mL in DMSO, ≥ 47.6 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9198 mL | 9.5991 mL | 19.1983 mL |
| 5 mM | 0.384 mL | 1.9198 mL | 3.8397 mL |
| 10 mM | 0.192 mL | 0.9599 mL | 1.9198 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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