1247819-59-5

Basic information

• Product Name: P 22077
• Synonyms: P 22077;1-(5-(2,4-difluorophenylthio)-4-nitrothiophen-2-yl)ethanone;1-[5-[(2,4-Difluorophenyl)thio]-4-n-itro-2-thienyl]-ethanone;Ethanone, 1-[5-[(2,4-difluorophenyl)thio]-4-nitro-2-thienyl]-;1-[5-[(2,4-Difluorophenyl)thio]-4-nitro-2-thienyl]ethanone P 22077;P 22077 1-[5-[(2,4-Difluorophenyl)thio]-4-nitro-2-thienyl]ethanone;1-[5-(2,4-Difluoro-phenylsulfanyl)-4-nitro-thiophen-2-yl]-ethanone
• CAS NO: 1247819-59-5
• Molecular Formula: C₁₂H₇F₂NO₃S₂
• Molecular Weight: 315.3156864
• Product Categories: Inhibitors
• Mol File: 1247819-59-5.mol

Chemical Properties

• Boiling Point: 395.4±42.0 °C(Predicted)
• Appearance: /
• Density: 1.53±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 25 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: P 22077(CAS DataBase Reference)
• NIST Chemistry Reference: P 22077(1247819-59-5)
• EPA Substance Registry System: P 22077(1247819-59-5)

Safety Data

• Hazardous Substances Data: 1247819-59-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
P22077 is used as a research compound for studying the role of USP7 in various cellular processes and its potential as a therapeutic target for cancer treatment.
Used in Cancer Research:
P22077 is used as an inhibitor of USP7 for destabilizing claspin and inducing p53-mediated apoptosis in neuroblastoma cells, as well as for destabilizing N-Myc in human neuroblastoma cells.
Used in Drug Combination Studies:
P22077 is used in combination with an Mdm2 inhibitor (Nutlin-3) to stabilize p53 levels in HCT116 colorectal carcinoma cells, potentially enhancing the therapeutic efficacy of p53-targeting drugs.

References

1) Tian?et al. (2011),?Characterization of Selective Ubiquitin and Ubiquitin-like Protease Inhibitors Using a Fluorescence-Based Multiplex Assay Format; Assay Drug Dev. Technol.?9?165 2) Altun?et al.?(2011),?Activity-based chemical proteomics accelerates inhibitor development for deubiquitinylating enzymes; Chem. Biol.?18?1401 3) Fan?et al.?(2013),?USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis;?Cell Death Dis.?4?e867 4) Tavana?et al.?(2016),?HAUSP deubiquitinates and stabilizes M-Myc in neuroblastoma; Nat. Med.?22?1180 5) Tavana?et al.?(2018),?Targeting HAUSP in both p53 wildtype and p53-mutant tumors; Cell Cycle?17?823

Upstream product

• 6310-09-4 2-acetyl-5-chlorothiophene 
• 42456-75-7 5-acetyl-2-chloro-3-nitrothiophene 
• 1996-44-7 2,4-difluorothiophenol 

Relevant articles and documents

Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors

Herpesvirus-associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with and stabilizes Mdm2, and represents one of the first examples that deubiquitinases oncogenic proteins. USP7 has been regarded as a potential drug target for cancer therapy. Inhibitors of USP7 have been recently shown to suppress tumor cell growth in vitro and in vivo. Based on leading USP7 inhibitors P5091 and P22077, we designed and synthesized a series of thiazole derivatives. The results of in vitro assays showed that the thiazole compounds exhibited low micromolar inhibition activity against both USP7 enzyme and cancer cell lines. The compounds induced cell death in a p53-dependent and p53-independent manner. Taken together, this study may provide thiazole compounds as a new class of USP7 inhibitors.

Selective dual inhibitors of the cancer-related deubiquitylating proteases USP7 and USP47

Inhibitors of the cancer-related cysteine isopeptidase human ubiquitin-specific proteases 7 (USP7) and 47 (USP47) are considered to have potential as cancer therapeutics, owing to their ability to stabilize the tumor suppressor p53 and to decrease DNA polymerase β(Polβ), both of which are potential anticancer effects. A new class of dual small molecule inhibitors of these enzymes has been discovered. Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines. Compound 1 has been shown to demonstrate modest activity in human xenograft multiple myeloma and B-cell leukemia in vivo models. This activity may be the result of dual inhibition of USP7 and USP47. To address issues regarding potency and developability, analogues of compound 1 have been synthesized and tested, leading to improvements in potency, solubility, and metabolic reactivity profile. Further optimization is expected to yield preclinical candidates and, ultimately, clinical candidates for the treatment of multiple myeloma, prostate cancer, and other cancers.