VLX-1570

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H17F2N3O6
Molecular Weight	469.3944
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[O-][N+](=O)C1=CC(\C=C2/CN(CC\C(=C/C3=CC(=C(F)C=C3)[N+]([O-])=O)C2=O)C(=O)C=C)=CC=C1F

InChI

InChIKey=SCKXBVLYWLLALY-CZCYGEDCSA-N

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+

HIDE SMILES / InChI

Molecular Formula	C23H17F2N3O6
Molecular Weight	469.3944
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	2
Optical Activity	NONE

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT02372240 | https://www.ncbi.nlm.nih.gov/pubmed/27264969 | https://www.ncbi.nlm.nih.gov/pubmed/27813535

Vivolux developed VLX-1570 as a small molecule proteasome 19S proteasome deubiquitinase (DUB) inhibitor. In addition, VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. VLX-1570 participated in phase I/II clinical trial in patients with myeloma. However, this study was terminated because of the dose-limiting toxicity was observed. Thus, the full clinical trial was put on hold. VLX1570 also inhibits ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Besides, was shown that VLX1570 modulated bio-cellular pathways that were essential for Waldenstrom macroglobulinemia (WM) cell survival. Thus, VLX1570 can be further studied for clinical use in patients with WM.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
19S-Proteasome Deubiquitinase 1 Target ID: 19S-Proteasome Deubiquitinase Sources: https://www.ncbi.nlm.nih.gov/pubmed/25854145	Inhibitor 8297	0.58 µM [IC50]
Ubiquitin carboxyl-terminal hydrolase 14 2 Target ID: P54578 Gene ID: 9097.0 Gene Symbol: USP14 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27264969	Inhibitor 8297
Ubiquitin carboxyl-terminal hydrolase isozyme L5 2 Target ID: Q9Y5K5 Gene ID: 51377.0 Gene Symbol: UCHL5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27813535	Inhibitor 8297

PubMed

Title	Date	PubMed
Synthesis and evaluation of derivatives of the proteasome deubiquitinase inhibitor b-AP15.	2015 Nov	25854145
The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells.	2016 Jun 6	27264969
USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment.	2016 May 24	27121063

Sample Use Guides

In Vivo Use Guide

VLX1570 IV (0.05, 0.15, 0.3, 0.6, 1.2, 2.0 mg/kg) on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:28:43 GMT 2023` Edited by `admin` on `Sat Dec 16 08:28:43 GMT 2023`
Record UNII	K6067N5M6N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VLX-1570

Common Name

English

(3E,5E)-3,5-BIS((4-FLUORO-3-NITROPHENYL)METHYLIDENE)-1-(PROP-2-ENOYL)AZEPAN-4-ONE

Systematic Name

English

VLX1570

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

428714