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P 22077

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Chemical Structure| 1247819-59-5 同义名 : -
CAS号 : 1247819-59-5
货号 : A106163
分子式 : C12H7F2NO3S2
纯度 : 99%+
分子量 : 315.316
MDL号 : MFCD22580421
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(158.57 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2% DMSO+30% PEG 300+2% Tween 80+water 3 mg/mL

生物活性
靶点

  • USP/UBP

    USP7, IC50:8.6 μM

    USP47, EC50:8.74 μM
描述 Deubiquitinating enzymes (DUBs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. More than the half of DUBs belong to the ubiquitin-specific protease (USP) subfamily. USP7 is the most widely studied DUB and is well known as herpes-associated USP (HAUSP). USP7 can influence the location, activation , and stability of its substrates[3]. P22077 is an inhibitor of USP7 with IC50 value of 6 and 10 μM for USP10 and USP7, respectively[4]. In vitro, P22077 activates p53 and its targeted gene p21 (cyclin-dependent kinase inhibitor 1) in human colon carcinoma HCT116 cells. P22077 greatly reduced the cell viability and induced apoptosis of IMR-32, NGP, CHLA-255, and SH-SY5Y cells but not that of NB-19 and SK-N-AS cells at concentration ranging in 1 - 20 μM. P22077 stabilized p53 by inducing HDM2 protein degradation, and augmented the cytotoxic effects of doxorubicin and etoposide in neuroblastoma cells. In vivo, administration P2207 at dose of 15 mg/kg daily for 3 weeks significantly inhibited tumor growth in the orthotopic neuroblastoma mouse model[5]. Treatment with P2207 on the dose of 20 mg/kg daily for 30 days significantly suppressed the growth of MYCN-amplified human neuroblastoma cell lines in xenograft mouse models[6].
作用机制 P22077 covalently modify the catalytic cysteine of USP7 and induce a conformational switch in the enzyme associated with active site rearrangement[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.17mL

0.63mL

0.32mL

15.86mL

3.17mL

1.59mL

31.71mL

6.34mL

3.17mL
参考文献

[1]Altun M, Kramer HB, et al. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol. 2011 Nov 23;18(11):1401-12.

[2]Tian X, Isamiddinova NS, et al. Characterization of selective ubiquitin and ubiquitin-like protease inhibitors using a fluorescence-based multiplex assay format. Assay Drug Dev Technol. 2011 Apr;9(2):165-73.

[3]Shan H, Li X, Xiao X, Dai Y, Huang J, Song J, Liu M, Yang L, Lei H, Tong Y, Zhou L, Xu H, Wu Y. USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia. Signal Transduct Target Ther. 2018 Oct 26;3:29.

[4]Weisberg EL, Schauer NJ, Yang J, Lamberto I, Doherty L, Bhatt S, Nonami A, Meng C, Letai A, Wright R, Tiv H, Gokhale PC, Ritorto MS, De Cesare V, Trost M, Christodoulou A, Christie A, Weinstock DM, Adamia S, Stone R, Chauhan D, Anderson KC, Seo HS, Dhe-Paganon S, Sattler M, Gray NS, Griffin JD, Buhrlage SJ. Inhibition of USP10 induces degradation of oncogenic FLT3. Nat Chem Biol. 2017 Dec;13(12):1207-1215.

[5]Fan YH, Cheng J, Vasudevan SA, Dou J, Zhang H, Patel RH, Ma IT, Rojas Y, Zhao Y, Yu Y, Zhang H, Shohet JM, Nuchtern JG, Kim ES, Yang J. USP7 inhibitor P22077 inhibits neuroblastoma growth via inducing p53-mediated apoptosis. Cell Death Dis. 2013 Oct 17;4(10):e867.

[6]Tavana O, Li D, Dai C, Lopez G, Banerjee D, Kon N, Chen C, Califano A, Yamashiro DJ, Sun H, Gu W. HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma. Nat Med. 2016 Oct;22(10):1180-1186.

[7]Pozhidaeva A, Valles G, Wang F, Wu J, Sterner DE, Nguyen P, Weinstock J, Kumar KGS, Kanyo J, Wright D, Bezsonova I. USP7-Specific Inhibitors Target and Modify the Enzyme's Active Site via Distinct Chemical Mechanisms. Cell Chem Biol. 2017 Dec 21;24(12):1501-1512.e5.