VLX1570

Catalog No.S8288 Batch:S828801

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Technical Data

Formula

C23H17F2N3O6
Molecular Weight 469.39 CAS No. 1431280-51-1
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description VLX1570 is a competitive inhibitor of proteasome DUB activity, with an IC50 of ~10 μM in vitro.
Targets
DUB [1]
(Cell-free assay)
~10 μM
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].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    OPM-2 MM cells

  • Concentrations

    0.5 μM

  • Incubation Time

    3 h

  • Method

    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. 
Animal Study:

[1]
  • Animal Models

    Female SCID mice

  • Dosages

    3 mg/kg

  • Administration

    i.v

Selleck's VLX1570 has been cited by 6 publications

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

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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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