1381291-36-6

Basic information

• Product Name: USP7-IN-1
• Synonyms: USP7-IN-1;4(3H)-Quinazolinone, 7-chloro-3-[[4-hydroxy-1-(1-oxo-3-phenylpropyl)-4-piperidinyl]methyl]-
• CAS NO: 1381291-36-6
• Molecular Formula: C₂₃H₂₄ClN₃O₃
• Molecular Weight: 425.90796
• Mol File: 1381291-36-6.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• CAS DataBase Reference: USP7-IN-1(CAS DataBase Reference)
• NIST Chemistry Reference: USP7-IN-1(1381291-36-6)
• EPA Substance Registry System: USP7-IN-1(1381291-36-6)

Safety Data

• Hazardous Substances Data: 1381291-36-6(Hazardous Substances Data)

Usage

General Description

USP7-IN-1 is a chemical compound that functions as an inhibitor of the ubiquitin-specific protease 7 (USP7). USP7 is a deubiquitinase enzyme that plays a key role in regulating various cellular processes, including DNA damage response, p53 regulation, and epigenetic modifications. Inhibition of USP7 with USP7-IN-1 has been shown to promote the degradation of oncoproteins, such as MDM2 and MDMX, leading to the activation of tumor suppressor pathways. Additionally, USP7 has been implicated in the replication of viruses, such as human cytomegalovirus, making USP7-IN-1 a potential therapeutic target for both cancer and viral infections. Further research on the pharmacological properties and potential therapeutic applications of USP7-IN-1 is ongoing.

Upstream product

• 1426340-66-0 tert-butyl 4-[(7-chloro-4-oxo-3,4-dihydroquinazolin-3-yl)methyl]-4-hydroxypiperidine-1-carboxylate 
• 31374-18-2 7-chloro-3,4-dihydroquinazolin-4-one 
• 501-52-0 3-Phenylpropionic acid 
• 89-77-0 2-Amino-4-chlorobenzoic acid 

Relevant articles and documents

Design, synthesis, biological evaluation and structure-activity relationship study of quinazolin-4(3H)-one derivatives as novel USP7 inhibitors

Recent research has indicated that the abnormal expression of the deubiquitinase USP7 induces tumorigenesis via multiple cell pathways, and in particular, the p53-MDM2-USP7 pathway is well understood. USP7 is emerging as a promising target for cancer therapy. However, there are limited reports on USP7 inhibitors. Here we report design, synthesis and biological evaluation of novel quinazolin-4(3H)-one derivatives as potent USP7 inhibitors. Our results indicated that the compounds C9 and C19 exhibited the greatest potency against the USP7 catalytic domain, with IC50 values of 4.86 μM and 1.537 μM, respectively. Ub-AMC assays further confirmed IC50 values of 5.048 μM for C9 and 0.595 μM for C19. MTT assays indicated that gastric cancer MGC-803 cells were more sensitive to these compounds than BGC-823 cells. Flow cytometry analysis revealed that C9 restricted cancer cell growth at the G0/G1 and S phases and inhibited the proliferation and clone formation of MGC-803 cells. Further biochemical experiments indicated that C9 decreased the MDM2 protein level and increased the levels of the tumour suppressors p53 and p21 in a dose-dependent manner. Docking studies predicted that solvent exposure of the side chains of C9 and C19 would uniquely form hydrogen bonds with Met407 of USP7. Additionally, C9 exhibited a remarkable anticancer effect in a zebrafish gastric cancer MGC-803 cell model. Our results demonstrated that quinazolin-4(3H)-one derivatives were suitable as leads for the development of novel USP7 inhibitors and especially for anti-gastric cancer drugs.