b-AP15

製品コードS4920 バッチS492002

印刷

化学情報

Chemical Structure Synonyms NSC687852 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H17N3O6
分子量 419.39 CAS No. 1009817-63-3
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 48 mg/mL (114.45 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
4%DMSO Corn oil
1.0mg/ml Taking the 1 mL working solution as an example, add 40 μL of 25 mg/ml clear DMSO stock solution to 960 μL of corn oil and mix evenly. 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 b-AP15 (NSC687852) is a deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM.
in vitro b-AP15 inhibits 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 results in a dose-dependent accumulation of the UbG76V-YFP reporter with IC50 of 0.8 μM, indicating impaired proteasome degradation. b-AP15 (1 μM) results in rapid accumulation of polyubiquitinated proteins in human colon carcinoma HCT-116 cells. b-AP15 (2.2 μM) increases the amounts of the cyclin-dependent kinases CDKN1A and CDKNIB and the tumor suppressor TP53 in a dose-dependent manner without altering the amounts of ornithine decarboxylase 1 (ODC1) in HCT-116 cells. b-AP15 (1 μM) results in G2/M phase cell-cycle arrest in HCT-116 cells, consistent with the accumulation of cell-cycle inhibitors. b-AP15 treatment increases the number of hypodiploid cells and is associated with increased amounts of apoptotic markers, including activated caspase-3, caspase-cleaved poly-ADP ribose polymerase (PARP) and cytokeratin-18 (CK18). b-AP15 is more toxic to HCT-116 cells as compared to immortalized epithelial cells (hTERT-RPE1) or peripheral blood mononuclear cells. b-AP15 inhibits deubiquitinating activity using a variety of substrates, including Ub-AMC, Ub-GFP22, ubiquitinated p53-binding protein homolog (HDM2), and K48- and K63-linked ubiquitin tetramer chains. [1] b-AP15 is an inhibitor of the UPS that induced cell death via induction of the lysosomal apoptosis pathway in a cathepsin-D dependent manner. b-AP15 elicits characteristic UPS defects including the accumulation of ubiquitin conjugates and cell cycle inhibitors such as p21, p27 and the tumor suppressor p53. b-AP15 inhibits the deubiquitinase activity of both cysteine DUBs, with USP14 being slightly more sensitive than UCHL5. b-AP15 induces apoptosis in cells over-expressing the anti-apoptotic Bcl-2 protein and in cells lacking the p53 gene. [2] b-AP15 (1 μM) inhibits ATP-induced IL-1β release from LPS-primed peritoneal macrophages. b-AP15 (1 μM) reduces the levels of cell death induced by nigericin treatment in THP-1 cells. b-AP15 (1 μM) significantly reduces the numbers of ASC specks formed after nigericin treatment in LPS-primed THP-1 cells. [3]
in vivo b-AP15 (5 mg/kg) shows significant antitumor activity in severe combined immunodeficiency (SCID) mice with FaDu squamous carcinoma xenografts. b-AP15 (5 mg/kg) significantly delays tumor onset in mice with HCT-116 colon carcinoma xenografts. [1]
特徴 Not a general deubiquitinase inhibitor. Has minimal inhibition on recombinant and cytosolic nonproteasomal cysteine deubiquitinases.

プロトコル(参考用のみ)

キナーゼアッセイ Deubiquitinase inhibition assays
For deubiquitinase inhibition assays, we incubate 19S regulatory particle (5 nM), 26S (5 nM) UCH-L1 (5 nM), UCH-L3 (0.3 nM), USP2CD (5 nM), USP7CD (5 nM), USP8CD, (5 nM) or BAP1 (5 nM) with DMSO or b-AP15 and monitored the cleavage of ubiquitin-AMC (1?03 nM) using a Wallac VICTOR Multilabel counter or a Tecan Infinite M1000 equipped with 380 nm excitation and 460 nm emission filters.
動物実験 動物モデル mice with HCT-116 colon carcinoma xenografts
投薬量 5 mg/kg
投与方法 intraperitoneal injection

カスタマーフィードバック

Data from [Data independently produced by , , Int J Biochem Cell Biol, 2016, 79:350-359. ]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma [ J Transl Med, 2024, 22(1):193] PubMed: 38388430
A carboxy-terminal ubiquitylation site regulates androgen receptor activity [ Commun Biol, 2024, 7(1):25] PubMed: 38182874
FAAH served a key membrane-anchoring and stabilizing role for NLRP3 protein independently of the endocannabinoid system [ Cell Death Differ, 2022, 10.1038/s41418-022-01054-4] PubMed: 36104448
Inhibition of proteasomal deubiquitinases USP14 and UCHL5 overcomes tyrosine kinase inhibitor resistance in chronic myeloid leukaemia [ Clin Transl Med, 2022, 12(9):e1038] PubMed: 36082692
Treatment with b-AP15 to Inhibit UCHL5 and USP14 Deubiquitinating Activity and Enhance p27 and Cyclin E1 for Tumors with p53 Deficiency [ Technol Cancer Res Treat, 2022, 21:15330338221119745] PubMed: 35971329
SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia [ Sci Adv, 2022, 8(3):eabj8357] PubMed: 35061527
MK2 degradation as a sensor of signal intensity that controls stress-induced cell fate [ Proc Natl Acad Sci U S A, 2021, 118(29)e2024562118] PubMed: 34272277
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] PubMed: 33979649
Regulation of Bax-dependent apoptosis by mitochondrial deubiquitinase USP30 [ Cell Death Discov, 2021, 7(1):211] PubMed: 34381024
Re-Evaluating the Mechanism of Action of α,β-Unsaturated Carbonyl DUB Inhibitors b-AP15 and VLX1570: A Paradigmatic Example of Unspecific Protein Cross-linking with Michael Acceptor Motif-Containing Drugs. [ J Med Chem, 2020, 9;63(7):3756-3762] PubMed: 32109059

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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