Avagacestat
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MedKoo CAT#: 500206

CAS#: 1146699-66-2

Description: Avagacestat, also known as BMS-708163, is an oral GSI designed for selective inhibition of Aβ synthesis currently in development for the treatment of mild to moderate and predementia AD. In addition to the desired effect on Aβ synthesis, GSIs affect Notch processing, which is thought to mediate some toxic adverse effects reported with this drug class.


Chemical Structure

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Avagacestat
CAS# 1146699-66-2

Theoretical Analysis

MedKoo Cat#: 500206
Name: Avagacestat
CAS#: 1146699-66-2
Chemical Formula: C20H17ClF4N4O4S
Exact Mass: 520.05952
Molecular Weight: 520.88
Elemental Analysis: C, 46.12; H, 3.29; Cl, 6.81; F, 14.59; N, 10.76; O, 12.29; S, 6.16

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Synonym: Avagacestat; BMS708163; BMS-708163; BMS 708163.

IUPAC/Chemical Name: (R)-2-(4-chloro-N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide

InChi Key: MKQKPLQMNCXTJE-VEZQGTPESA-L

InChi Code: InChI=1S/C22H25N6O8P.2Na/c1-2-23-22(29)27-19-16-20(25-11-24-19)28(12-26-16)21-18-17(14(34-21)10-33-37(30,31)32)35-15(36-18)9-8-13-6-4-3-5-7-13;;/h3-9,11-12,14-15,17-18,21H,2,10H2,1H3,(H2,30,31,32)(H2,23,24,25,27,29);;/q;2*+1/p-2/b9-8+;;/t14-,15+,17-,18-,21-;;/m1../s1

SMILES Code: O=C(N)[C@H](N(CC1=CC=C(C2=NOC=N2)C=C1F)S(=O)(C3=CC=C(Cl)C=C3)=O)CCC(F)(F)F

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 520.88 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens R. A contrast in safety, pharmacokinetics, and pharmacodynamics across age groups after a single 50-mg oral dose of the γ-secretase inhibitor avagacestat. Br J Clin Pharmacol. 2012 May 23. doi: 10.1111/j.1365-2125.2012.04339.x. [Epub ahead of print] PubMed PMID: 22616739.

2: Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens RC. Multicenter, randomized, double-blind, placebo-controlled, single-ascending dose study of the oral γ-secretase inhibitor BMS-708163 (Avagacestat): tolerability profile, pharmacokinetic parameters, and pharmacodynamic markers. Clin Ther. 2012 Mar;34(3):654-67. Epub 2012 Feb 28. PubMed PMID: 22381714.

3: Mitani Y, Yarimizu J, Saita K, Uchino H, Akashiba H, Shitaka Y, Ni K, Matsuoka N. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J Neurosci. 2012 Feb 8;32(6):2037-50. PubMed PMID: 22323718.

4: Hartley RF, Huang Y, Cassidy M, Razler TM, Qian F, Hussain MA. Degradation kinetics and mechanism of an oxadiazole derivative, design of a stable drug product for BMS-708163, a γ-secretase inhibitor drug candidate. J Pharm Sci. 2012 Sep;101(9):3124-33. doi: 10.1002/jps.23050. Epub 2012 Jan 19. PubMed PMID: 22262489.

5: Lu Y, Zhang L, Nolan CE, Becker SL, Atchison K, Robshaw AE, Pustilnik LR, Osgood SM, Miller EH, Stepan AF, Subramanyam C, Efremov I, Hallgren AJ, Riddell D. Quantitative pharmacokinetic/pharmacodynamic analyses suggest that the 129/SVE mouse is a suitable preclinical pharmacology model for identifying small-molecule γ-secretase inhibitors. J Pharmacol Exp Ther. 2011 Dec;339(3):922-34. Epub 2011 Sep 19. PubMed PMID: 21930801.

6: Gu H, Deng Y, Wang J, Aubry AF, Arnold ME. Development and validation of sensitive and selective LC-MS/MS methods for the determination of BMS-708163, a gamma-secretase inhibitor, in plasma and cerebrospinal fluid using deprotonated or formate adduct ions as precursor ions. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2319-26. Epub 2010 Jul 6. PubMed PMID: 20674522.



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