VLX1570

製品コードS8288 バッチS828801

印刷

化学情報

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

C23H17F2N3O6
分子量 469.39 CAS No. 1431280-51-1
Solubility (25°C)* 体外 DMSO 93 mg/mL (198.12 mM)
Water Insoluble
Ethanol Insoluble
* <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 VLX1570 is a competitive inhibitor of proteasome DUB activity, with an IC50 of ~10 μM in vitro.
in vitro VLX1570 is an analogue of b-AP15 that shows higher potency and improved solubility. VLX1570 preferentially inhibits proteasomal DUB activity while not inhibiting the activities of a panel of non-proteasomal DUBs. VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Treatment of multiple myeloma cells with VLX1570 induces the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. VLX1570 induces the expression of the chaperone HSP70B′, the oxidative stress marker Hmox-1, and the ER stress marker XBP-1s. VLX1570 is retained in cells after removal of drug and that USP14 was engaged by drug 17 hours after wash-out, as evidenced by thermal stabilization and persistent enzyme inhibition[1].
in vivo VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Treatment with VLX1570 is found to lead to extended survival in xenograft models of multiple myeloma. The in vivo IC50 for inhibition of proteasome DUB activity and induction of apoptosis is <1 μM, with multiple myeloma cells showing greater levels of sensitivity compared to other tumor types. The lower IC50 for activity in vivo is presumably due to rapid drug uptake and enrichment in cells[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 OPM-2 MM cells
濃度 0.5 μM
反応時間 3 h
実験の流れ

OPM-2 MM cells are exposed to 0.5 μM VLX1570 for 3 hours and 25 μg whole cell lysates are subsequently labeled with Ub-VS (1 μM), followed by SDS gel electrophoresis and immunoblotting with USP14 or UCHL5 antibodies. 
動物実験 動物モデル Female SCID mice
投薬量 3 mg/kg
投与方法 i.v

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：

A carboxy-terminal ubiquitylation site regulates androgen receptor activity [ Commun Biol, 2024, 7(1):25] PubMed: 38182874
Histone deacetylase inhibitor, panobinostat, exerts anti-proliferative effect with partial normalization from aberrant epigenetic states on granulosa cell tumor cell lines [ PLoS One, 2022, 17(7):e0271245] PubMed: 35802681
VLX1570 induces apoptosis through the generation of ROS and induction of ER stress on leukemia cell lines [ Cancer Sci, 2021, 112(8):3302-3313] PubMed: 34032336
Deubiquitinase Inhibitors Impair Leukemic Cell Migration Through Cofilin Oxidation and Alteration of Actin Reorganization [ Front Pharmacol, 2021, 12:778216] PubMed: 35069199
Histone Deacetylase Inhibitor, Panobinostat Exerts Anti-proliferative Effect with Partial Normalization from Aberrant Epigenetic States on Granulosa Cell Tumor [ Research Square, 2021, 10.21203/rs.3.rs-265240/v1] PubMed: None
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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