| Identification | Back Directory | [Name]
P 22077 | [CAS]
1247819-59-5 | [Synonyms]
P 22077
CS-1115
P 22077; P-22077
P 22077 USP/EP/BP
USP7/USP47 Inhibitor, 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-Difluoro-phenylsulfanyl)-4-nitro-thiophen-2-yl]-ethanone
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 | [Molecular Formula]
C12H7F2NO3S2 | [MDL Number]
MFCD22580421 | [MOL File]
1247819-59-5.mol | [Molecular Weight]
315.316 |
| Chemical Properties | Back Directory | [Melting point ]
146 - 148°C | [Boiling point ]
395.4±42.0 °C(Predicted) | [density ]
1.53±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to 25 mg/ml) | [form ]
solid | [color ]
Off-white | [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. |
| Hazard Information | Back Directory | [Description]
P22077 (1247819-59-5) is a selective (tested against 23 other DUBs) inhibitor of USP7 (IC50?= 8 μM) and the closely related USP47.1,2?It destabilizes claspin, a scaffolding protein involved in regulating Chk1 kinase, a DNA damage response enzyme.2?P22077 inhibits neuroblastoma growth?via?induction of p53-mediated apoptosis.3?N-Myc was destabilized by P22077 inhibition of USP7 in human neuroblastoma cells.4?It was able to stabilize p53 levels in conjunction with an Mdm2 inhibitor (Nutlin-3,?Cat# 10-1350)?in HCT116 colorectal carcinoma cells.5 | [Uses]
P22077 is an analog of the ubiquitin-specific protease (USP7) inhibitor P5091. It inhibits USP7, as well. | [Synthesis]
1. 2-Acetyl-5-chlorothiophene (4.00 g, 24.8 mmol) was added in batches to fuming nitric acid (24 mL) cooled in an ice bath.
2. The reaction mixture was stirred at room temperature for 30 minutes and then poured into 200 mL of ice water.
3. The precipitated solid was extracted with ether, and the organic phase was dried, filtered, and concentrated in vacuum to afford the crude product 1-(5-chloro-4-nitrothiophen-2-yl)ethan-1-one (4.50 g, yellow solid), which did not require further purification.
4. 2,4-difluorothiophenol (4.30 g, 29.4 mmol) was added to a solution of sodium methanolate (1.40 g, 26.3 mmol) in methanol (250 mL).
5. The mixture was stirred at room temperature for 20 minutes before the crude product 1-(5-chloro-4-nitrothiophen-2-yl)ethan-1-one (5.50 g) was added.
6. The mixture was stirred overnight and then water (250 mL) was added, the solid formed was collected by filtration and dried under vacuum at 40 °C. The product was reconstituted by acetonitrile over a 2-minute period.
7. The product was recrystallized twice by acetonitrile to give 1-(5-((2,4-difluorophenyl)thio)-4-nitrothiophen-2-yl)ethanone (3.30 g, 39% yield) as a white solid.
8. 1H NMR (300 MHz, DMSO) δ 8.50, 8.00, 7.97, 7.95, 7.9, 7.71, 7.70, 7.68, 7.67, 7.65, 7.64, 7.43, 7.40, 7.37, 2.50. | [Enzyme inhibitor]
This ubiquitin cycle inhibitor (FW = 315.33 g/mol; CAS 1247819-59-5;
Solubility: 60 mg/mL DMSO), also known as 1-[5-[ (2,4-
difluorophenyl) thio]-4-nitro-2-thienyl]ethanone, targets Ubiquitin-Specific
Peptidase-7 (or USP-7) with an EC50 value of 8.6 μM. P22077 also inhibits
the structurally related peptidase USP-47. | [in vivo]
P 22077 (15 mg/kg, i.p. 21 days) shows potent antitumor activities in an xenograft mouse model bearing IMR-32-derived tumors; P 22077 also exhibits antitumor effects after treatment at 10 mg/kg for 14 days in mice bearing SH-SY5Y-derived tumors, and at 20 mg/kg for 12 days in mice bearing NGP-derived tumors[2]. | [storage]
Store at 4°C | [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 |
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