b-AP15 (NSC687852) --- Deubiquitinases Inhibitor

b-AP15 (NSC686852) is a potent and selective deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM. It inhibits the activity of two 19S regulatory-particle-associated deubiquitinases, UCHL5 and USP14, resulting in accumulation of polyubiquitin. It has minimal inhibition of UCHL-1, UCHL-3, USP2, USP7, USP, BAP1 and proteasome activity. b-AP15 induces apoptosis by cathepsin D-dependent caspase-cleavage (IC50 ~0.5 μM) and displays antitumor activity in vivo.

Product information

CAS Number: 1009817-63-3

Molecular Weight: 419.39

Formula: C22H17N3O6

Synonym:

NSC686852

Chemical Name: (3E,5E)-1-acryloyl-3,5-bis(4-nitrobenzylidene)piperidin-4-one

Smiles: C=CC(=O)N1C/C(=C\C2C=CC(=CC=2)[N+]([O-])=O)/C(=O)/C(/C1)=C/C1C=CC(=CC=1)[N+]([O-])=O

InChiKey: GFARQYQBWJLZMW-JYFOCSDGSA-N

InChi: InChI=1S/C22H17N3O6/c1-2-21(26)23-13-17(11-15-3-7-19(8-4-15)24(28)29)22(27)18(14-23)12-16-5-9-20(10-6-16)25(30)31/h2-12H,1,13-14H2/b17-11+,18-12+

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

b-AP15 was used at 10 µM final concentration in various in vitro assays.

In Vivo:

b-AP15 was dosed to mice with HCT-116 colon carcinoma xenografts by intraperitoneal injection at 5 mg/Kg. formulation is Cremophor EL and polyethylene glycol 400 (1:1).

References:

1. Berndtsson M, et al. Induction of the lysosomal apoptosis pathway by inhibitors of the ubiquitin-proteasome system. (2009) Int J Cancer. 124(6):1463-9.
2. D'Arcy P, et al. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. (2011) Nat Med. 17(12):1636-40.

Products are for research use only. Not for human use.

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