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Chemical Structure| 1431280-51-1 Chemical Structure| 1431280-51-1

Structure of VLX1570
CAS No.: 1431280-51-1

Chemical Structure| 1431280-51-1

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VLX1570 is a deubiquitinylating enzyme DUB competitive inhibitor with an IC50 of approximately 10 μM in vitro and shows coinhibition of the deubiquitinating enzymes, like USP14 and UCHL5.

Synonyms: VLX1570

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Product Details of VLX1570

CAS No. :1431280-51-1
Formula : C23H17F2N3O6
M.W : 469.39
SMILES Code : O=C1/C(CN(C(C=C)=O)CC/C1=C/C2=CC=C(F)C([N+]([O-])=O)=C2)=C\C3=CC=C(F)C([N+]([O-])=O)=C3
Synonyms :
VLX1570
MDL No. :MFCD28502165

Safety of VLX1570

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • DUB

    DUB, IC50:~10 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
HNT34 cells 273 nM HNT34 cells showed moderate sensitivity to VLX1570 with an IC50 of 273 nM. PMC8470745
Kasumi-1 cells 260 nM Kasumi-1 cells showed moderate sensitivity to VLX1570 with an IC50 of 260 nM. PMC8470745
MOLM-14 cells 204 nM MOLM-14 cells showed higher sensitivity to VLX1570 with an IC50 of 204 nM. PMC8470745
KG1a cells 307 nM KG1a cells showed lower sensitivity to VLX1570 with an IC50 of 307 nM. PMC8470745
Primary WM tumor cells 250 nM 12 h To evaluate the apoptosis-inducing effect of VLX1570 on primary WM cells, results showed that VLX1570 induced apoptosis and PARP-1 cleavage at 250 nM. PMC5148058
BCWM.1/BR cells 29 nM 72 h To evaluate the cytotoxicity of VLX1570 on BCWM.1/BR cells, results showed that VLX1570 effectively inhibited cell viability at 29 nM. PMC5148058
WM cell lines and drug-resistant subclones 20 nM 72 h To assess the sensitivity of WM cells to VLX1570, results showed that all WM cells were sensitive to VLX1570, with BCWM.1 cells being the most sensitive, showing 50% loss of viability at 20 nM VLX1570. PMC5148058
LNCaP cells 5 μM 15 min VLX1570 markedly increased the overall levels of high-molecular weight ubiquitylated proteins but did not result in AR ubiquitylation, indicating that the high molecular weight AR species generated by VLX1570 were not due to polyubiquitylation PMC10770046
VCaP cells 2.5 or 5.0 μM 4 h VLX1570 significantly decreased AR in DHT-treated VCaP cells and increased high molecular weight AR, indicating a more pronounced effect of VLX1570 on AR in the presence of DHT PMC10770046
C4-2 cells 2.5 or 5.0 μM 4 h VLX1570 significantly decreased AR in DHT-treated cells and increased high molecular weight AR, indicating a more pronounced effect of VLX1570 on AR in the presence of DHT PMC10770046
H1299 cells 1.25, 2.5, 5, 10, 25, 50, 100, 200, 400 nM 72 h Evaluate the effect of VLX1570 on the viability of H1299 cells, results showed that VLX1570 significantly inhibited cell proliferation PMC8742231
H460 cells 1.25, 2.5, 5, 10, 25, 50, 100, 200, 400 nM 72 h Evaluate the effect of VLX1570 on the viability of H460 cells, results showed that VLX1570 significantly inhibited cell proliferation PMC8742231
A549 cells 1.25, 2.5, 5, 10, 25, 50, 100, 200, 400 nM 72 h Evaluate the effect of VLX1570 on the viability of A549 cells, results showed that VLX1570 significantly inhibited cell proliferation PMC8742231
U2OS cells 5 μM and 20 μM 1 h To identify covalent targets of VLX1570 through chemical proteomics, results showed multiple covalent targets were identified, with CIAPIN1 being the most significant PMC7152998
HL-60 50 nM 3 h VLX1570 induced the genetic pathway involved in “heat shock transcription factor 1 (HSF1) activation”, “HSF1 dependent transactivation”, and “Regulation of HSF1 mediated heat shock response”. PMC8353915

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice A673 and TC-71 xenograft models Intraperitoneal injection 4.4 mg/kg Daily, continuous treatment Evaluate the inhibitory effect of VLX1570 on tumor growth, results showed that VLX1570 significantly inhibited tumor growth PMC5484002
Mice WM xenograft model Intraperitoneal injection 4.4 mg/kg Every alternate day for 21 days To evaluate the anti-tumor activity of VLX1570 in WM xenograft mice, results showed that VLX1570 significantly reduced tumor volume and growth, and prolonged survival. PMC5148058
Zebrafish Zebrafish embryo model Added to water 1 µM 72 hours VLX1570 significantly inhibited the growth and spread of KG1a and MOLM-14 cells. PMC8470745

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.13mL

0.43mL

0.21mL

10.65mL

2.13mL

1.07mL

21.30mL

4.26mL

2.13mL

References

[1]Paulus A, Akhtar S, et al. Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells. Blood Cancer J. 2016 Nov 4;6(11):e492.

[2]Wang X, Mazurkiewicz M, et al. The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. Sci Rep. 2016 Jun 6;6:26979.

[3]Vogel RI, Pulver T, Heilmann W, Mooneyham A, Mullany S, Zhao X, Shahi M, Richter J, Klein M, Chen L, Ding R, Konecny G, Kommoss S, Winterhoff B, Ghebre R, Bazzaro M. USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment. Oncotarget. 2016 May 24;7(21):30962-76.

[4]Wang X, Mazurkiewicz M, Hillert EK, Olofsson MH, Pierrou S, Hillertz P, Gullbo J, Selvaraju K, Paulus A, Akhtar S, Bossler F, Khan AC, Linder S, D'Arcy P. The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. Sci Rep. 2016 Jun 6;6:26979.

[5]Mazurkiewicz M, Hillert EK, Wang X, Pellegrini P, Olofsson MH, Selvaraju K, D'Arcy P, Linder S. Acute lymphoblastic leukemia cells are sensitive to disturbances in protein homeostasis induced by proteasome deubiquitinase inhibition. Oncotarget. 2017 Mar 28;8(13):21115-21127.

[6]Paulus A, Akhtar S, Caulfield TR, Samuel K, Yousaf H, Bashir Y, Paulus SM, Tran D, Hudec R, Cogen D, Jiang J, Edenfield B, Novak A, Ansell SM, Witzig T, Martin P, Coleman M, Roy V, Ailawadhi S, Chitta K, Linder S, Chanan-Khan A. Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells. Blood Cancer J. 2016 Nov 4;6(11):e492.

[7]Shukla N, Somwar R, Smith RS, Ambati S, Munoz S, Merchant M, D'Arcy P, Wang X, Kobos R, Antczak C, Bhinder B, Shum D, Radu C, Yang G, Taylor BS, Ng CK, Weigelt B, Khodos I, de Stanchina E, Reis-Filho JS, Ouerfelli O, Linder S, Djaballah H, Ladanyi M. Proteasome Addiction Defined in Ewing Sarcoma Is Effectively Targeted by a Novel Class of 19S Proteasome Inhibitors. Cancer Res. 2016 Aug 1;76(15):4525-34.

 

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