B-AP15

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

B-AP15(NSC687852) 是 26S 蛋白酶体去泛素化酶 UCHL5 和 Usp14 的特异性抑制剂。

B-AP15(NSC687852) is a specific inhibitor of the deubiquitinating enzymes UCHL5 and Usp14 of the 26S proteasome. It blocks the deubiquitinating activity of the 26S proteasome.(In Vitro):Purified 19S proteasomes (5 nM) are treated with indicated concentrations of b-AP15 and DUB activity is determined by detectionof Ub-AMC cleavage. The IC50 value (2.1±0.411 μM) is determined from log concentration curves in Graph Pad Prism using non linear regression analysis. b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that is insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. The ability of b-AP15 is determined to inhibit proteasome deubiquitinase activity using Ub-AMC as the substrate. An IC50 of 16.8±2.8 μM is observed. b-AP15 is a specific USP14 and UCHL5 inhibitor, which blocks growth and induces apoptosis in MM cells.(In Vivo):b-AP15 (2.5 mg/kg) inhibits tumor growth in syngenic mice models with less frequent administration schedules. We administered b-AP15 to C57BL/6J mice with Lewis lung carcinomas (LLCs) using a 2-d-on, 2-d-off schedule and to BALB/c mice with orthotopic breast carcinoma (4T1) using a 1-d-on, 3-d-off schedule. b-AP15 significantly inhibited tumor growth in both models, with T/C=0.16 (P≤0.01) for the C57BL/6J mice and T/C=0.25 (P≤0.001) for the BALB/c mice. A reduction in the number of pulmonary metastases also is observed in the group of mice with 4T1 breast carcinomas treated with b-AP15.

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b-AP15 | USP14 Inhibitor III | UCHL5UCH37 Inhibitor II | NSC687852.

Proteasome/Ubiquitin

DUB

UCH-L5

Cancer

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1009817-63-3

419.39

C22H17N3O6

>98% (HPLC)

DMSO: 48 mg/mL warmed (114.45 mM)

O=C1/C(CN(C(C=C)=O)C/C1=C\C2=CC=C([N+]([O-])=O)C=C2)=C/C3=CC=C([N+]([O-])=O)C=C3

(3E,5E)-1-acryloyl-3,5-bis(4-nitrobenzylidene)piperidin-4-one.

(-20℃)

With Ice Pack

≥ 2 years