A potent inhibitor of γ-secretase
Technical Support & Resources

Visit our FAQ

Contact Us

Toll Free Phone (USA and Canada Only): (888) 526-5351
Direct Phone: (734) 975-3888

Request Technical Support

Technical Support Request

To streamline the process attach the appropriate questionnaire to your inquiry.

Download IHC QuestionnaireDownload WB Questionnaire

View Our Privacy Statement for details on how we use and protect your data. In addition, this site is protected by hCaptcha and its Privacy Policy and Terms of Service apply.

Avagacestat

Item No. 16711

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
(2R)-2-[[(4-chlorophenyl)sulfonyl][[2-fluoro-4-(1,2,4-oxadiazol-3-yl)phenyl]methyl]amino]-5,5,5-trifluoro-pentanamide
CAS Number
1146699-66-2
Synonyms
  • BMS 708163
Molecular Formula
C20H17ClF4N4O4S
Formula Weight
520.9
Purity
≥98%
Formulation
A crystalline solid
Solubility(Learn about Variance in Solubility)
DMF: 2 mg/mlDMSO: 15 mg/mlDMSO:PBS(pH 7.2) (1:2): 0.3 mg/mlEthanol: 5 mg/ml
λmax
244 nm
SMILES
O=S(N([C@@H](C(N)=O)CCC(F)(F)F)CC1=CC=C(C2=NOC=N2)C=C1F)(C3=CC=C(Cl)C=C3)=O
InChi Code
InChI=1S/C20H17ClF4N4O4S/c21-14-3-5-15(6-4-14)34(31,32)29(17(18(26)30)7-8-20(23,24)25)10-13-2-1-12(9-16(13)22)19-27-11-33-28-19/h1-6,9,11,17H,7-8,10H2,(H2,26,30)/t17-/m1/s1
InChi Key
XEAOPVUAMONVLA-QGZVFWFLSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
Recommended Products

Certificates of Analysis & Batch Specific Data

Provide batch numbers separated by commas to download or request available product inserts, QC sheets, certificates of analysis, data packs, and GC-MS data.

Download most recent Certificate of Analysis for this product

    1 mg

    $49

    Add

    5 mg

    $213

    Add

    10 mg

    $376

    Add
    Product Description

    γ-Secretase is a protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors and β-amyloid precursor protein (APP), within the transmembrane domain.1,2 Avagacestat is a potent, orally bioavailable inhibitor of γ-secretase that more potently inhibits the cleavage of APP to Aβ40 than signaling through Notch (IC50s = 0.30 and 58 nM, respectively).3 It shows good pharmacokinetics in rats, dogs, and humans and passes the blood-brain barrier, reducing plasma, brain, and cerebrospinal fluid Aβ40 levels.3,4 While suppressing the production of Aβ38, Aβ40, and Aβ42, γ-secretase inhibitors, including avagacestat, increase the level of APP β-C-terminal fragment, both in vitro and in vivo, altering cell function.5 Avagacestat may impact Notch signaling in vivo, although it is generally considered a “Notch-sparing” γ-secretase inhibitor.6

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Andersson, E.R., and Lendahl, U. Therapeutic modulation of Notch signalling - are we there yet? Nat. Rev. Drug Discov. 13(5), 357-378 (2014).

    2. Jurisch-Yaksi, N., Sannerud, R., and Annaert, W. A fast growing spectrum of biological functions of γ-secretase in development and disease. Biochim. Biophys. Acta 1828(12), 2815-2827 (2013).

    3. Gillman, K.W., Starrett, J.E., Jr., Parker, M.F., et al. Discovery and evaluation of BMS-708163, a potent, selective and orally bioavailable γ-secretase inhibitor. ACS Med. Chem. Lett. 1(3), 120-124 (2010).

    4. Albright, C.F., Dockens, R.C., Meredith, J.E., Jr., et al. Pharmacodynamics of selective inhibition of γ-secretase by avagacestat. J. Pharmacol. Exp. Ther. 344(3), 686-695 (2013).

    5. 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. Neurosci. 32(6), 2037-2050 (2012).

    6. Crump, C.J., Castro, S.V., Wang, F., et al. BMS-708,163 targets presenilin and lacks notch-sparing activity. Biochemistry 51(37), 7209-7211 (2012).