Avagacestat (BMS-708163)

Catalog No.S1262 Batch:S126203

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Technical Data

Formula

C20H17ClF4N4O4S
Molecular Weight 520.88 CAS No. 1146699-66-2
Solubility (25°C)* In vitro DMSO 100 mg/mL (191.98 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
1.65mg/ml Taking the 1 mL working solution as an example, add 50 μL of 33 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.
Targets
Aβ42 [1]
(in H4-8Sw cells)		 Aβ40 [1]
(in H4-8Sw cells)
0.27 nM 0.3 nM
In vitro BMS-708163 exhibits weaker selectivity for inhibition of Notch processing with 193-fold IC50 value. [1]
In vivo Oral administration of BMS-708163 significantly reduces Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs. BMS-708163 has no dose-limiting effects in dogs (3 mg/kg during 6 months), with a high brain to plasma ratio (2.4). [1]
Features Appears to be more “notch sparing” than semagacestat (LY450139).

Protocol (from reference)

Animal Study:[1]
  • Animal Models

    Female Harlan Sprague-Dawley rats or ATM-405-142K9 with 7- 10 month old Na?ve, grade II beagles

  • Dosages

    10 mg/kg (rats) or 2.5 mg/kg (dogs)

  • Administration

    Dosed daily by oral gavage

Customer Product Validation

Data from [Stem Cells, 2014, 32(1), 301-12]

Data from [Stem Cells, 2014, 32(1), 301-12]

Data from [Data independently produced by J Biol Chem, 2014, 289(30), 20871-8]

Data from [Data independently produced by , , Sci Rep, 2016, 6:33427]

Selleck's Avagacestat (BMS-708163) has been cited by 24 publications

Multi-omics characterization of autophagy-related molecular features for therapeutic targeting of autophagy [ Nat Commun, 2022, 13(1):6345] PubMed: 36289218
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Structural basis of γ-secretase inhibition and modulation by small molecule drugs [ Cell, 2021, 184(2):521-533.e14] PubMed: 33373587
Carboxy-terminal fragment of amyloid precursor protein mediates lipid droplet accumulation upon γ-secretase inhibition [ Biochem Biophys Res Commun, 2021, 570:137-142] PubMed: 34280617
Activation of notch 3/c-MYC/CHOP axis regulates apoptosis and promotes sensitivity of lung cancer cells to mTOR inhibitor everolimus. [ Biochem Pharmacol, 2020, 175:113921] PubMed: 32201213
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance [ Cancer Cell, 2019, 36(1):68-83] PubMed: 31257073
EGFL7 Antagonizes NOTCH Signaling and Represents a Novel Therapeutic Target in Acute Myeloid Leukemia. [ Clin Cancer Res, 2019, 10.1158/1078-0432.CCR-19-2479] PubMed: 31672772
Wild-type TP53 defined gamma-secretase inhibitor sensitivity and synergistic activity with doxorubicin in GSCs. [ Am J Cancer Res, 2019, 9(8):1734-1745] PubMed: 31497354
Iron dysregulates APP processing accompanying with sAPPα cellular retention and β-secretase inhibition in rat cortical neurons [Chen YT, et al. Acta Pharmacol Sin, 2018, 39(2):177-183] PubMed: 28836584

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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