WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206324
CAS#: 1431280-51-1
Description: VLX1570 is an inhibitor of the 19S proteasome-specific deubiquitylating enzymes (DUBs) USP14 and UCHL5, with apoptosis-inducing and antineoplastic activities. Upon administration, VLX1570 specifically binds to both USP14 and UCHL5, thereby blocking their deubiquitylating activity. This blocks the ubiquitin proteasome degradation pathway, prevents the degradation of defective proteins, and leads to an accumulation of poly-ubiquitylated proteins. This induces the unfolded protein response (UPR) and results in both the induction of tumor cell apoptosis and the inhibition of tumor cell growth.
MedKoo Cat#: 206324
Name: VLX1570
CAS#: 1431280-51-1
Chemical Formula: C23H17F2N3O6
Exact Mass: 469.1085
Molecular Weight: 469.4008
Elemental Analysis: C, 58.85; H, 3.65; F, 8.09; N, 8.95; O, 20.45
VLX1570, purity > 98%, is in stock.
Synonym: VLX-1570, VLX1570, VLX 1570
IUPAC/Chemical Name: 1-acryloyl-3,5-bis((Z)-4-fluoro-3-nitrobenzylidene)azepan-4-one
InChi Key: SCKXBVLYWLLALY-CQRYCMKKSA-N
InChi Code: InChI=1S/C23H17F2N3O6/c1-2-22(29)26-8-7-16(9-14-3-5-18(24)20(11-14)27(31)32)23(30)17(13-26)10-15-4-6-19(25)21(12-15)28(33)34/h2-6,9-12H,1,7-8,13H2/b16-9-,17-10-
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
The following data is based on the product molecular weight 469.4008 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: 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. doi: 10.18632/oncotarget.15501. PubMed PMID: 28423502; PubMed Central PMCID: PMC5400570.
2: 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. doi: 10.1038/bcj.2016.93. PubMed PMID: 27813535; PubMed Central PMCID: PMC5148058.
3: 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. Corrigendum: The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. Sci Rep. 2016 Jul 29;6:30667. doi: 10.1038/srep30667. PubMed PMID: 27472448; PubMed Central PMCID: PMC4966493.
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. doi: 10.1038/srep26979. Erratum in: Sci Rep. 2016 Jul 29;6:30667. PubMed PMID: 27264969; PubMed Central PMCID: PMC4893612.
5: 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. doi: 10.1158/0008-5472.CAN-16-1040. Epub 2016 Jun 2. PubMed PMID: 27256563; PubMed Central PMCID: PMC5484002.
6: 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. doi: 10.18632/oncotarget.8821. PubMed PMID: 27121063; PubMed Central PMCID: PMC5058731.
7: Wang X, D'Arcy P, Caulfield TR, Paulus A, Chitta K, Mohanty C, Gullbo J, Chanan-Khan A, Linder S. Synthesis and evaluation of derivatives of the proteasome deubiquitinase inhibitor b-AP15. Chem Biol Drug Des. 2015 Nov;86(5):1036-48. doi: 10.1111/cbdd.12571. Epub 2015 May 27. PubMed PMID: 25854145; PubMed Central PMCID: PMC4846425.
Note: MedKoo has licensed VLX1570 patent from Vivolux, AB. MedKoo obtained a non-exclusive license for commercial sales of the VLX1570 substance for non-clinical research use. VLX1570 was covered by patents: WO 2013058691, etc.
