VLX1570

Catalog No.S8288

For research use only.

VLX1570 is a competitive inhibitor of proteasome DUB activity, with an IC50 of ~10 μM in vitro.

VLX1570 Chemical Structure

CAS No. 1431280-51-1

Selleck's VLX1570 has been cited by 5 Publications

Purity & Quality Control

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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 Research:

[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 Research:

[1]

  • Animal Models: Female SCID mice
  • Dosages: 3 mg/kg
  • Administration: i.v

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 469.39
Formula

C23H17F2N3O6

CAS No. 1431280-51-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C=CC(=O)N1CCC(=CC2=CC(=C(C=C2)F)[N+](=O)[O-])C(=O)C(=CC3=CC(=C(C=C3)F)[N+](=O)[O-])C1

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02372240 Terminated Drug: VLX1570 and dexamethasone Multiple Myeloma Vivolux AB|Theradex April 8 2015 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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