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Chemical Structure| 1247819-59-5 Chemical Structure| 1247819-59-5

Structure of P 22077
CAS No.: 1247819-59-5

Chemical Structure| 1247819-59-5

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P22077 is an inhibitor of ubiquitin specific protease USP7 (EC50 = 8.6 μM). P22077 also inhibits the deubiquitinase USP47.

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Product Details of P 22077

CAS No. :1247819-59-5
Formula : C12H7F2NO3S2
M.W : 315.32
SMILES Code : CC(C1=CC([N+]([O-])=O)=C(SC2=CC=C(F)C=C2F)S1)=O
MDL No. :MFCD22580421
InChI Key :RMAMGGNACJHXHO-UHFFFAOYSA-N
Pubchem ID :46931953

Safety of P 22077

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H319-H332-H372-H400
Precautionary Statements:P260-P264-P270-P273-P280-P301+P312+P330-P304+P312-P305+P351+P338-P314-P337+P313-P391-P501
Class:9
UN#:3077
Packing Group:

Isoform Comparison

Biological Activity

Target
  • USP/UBP

    USP47, EC50:8.74 μM

    USP7, IC50:8.6 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
IMR-32 10 μM 24 hours P22077 significantly induces apoptosis in IMR-32 cells PMC3920959
SH-SY5Y 10 μM 24 hours P22077 significantly induces apoptosis in SH-SY5Y cells PMC3920959
LA-N-6 10 μM 24 hours P22077 overcomes chemoresistance in LA-N-6 cells PMC3920959
Huh7 cells 10 µM or 20 µM 24 hours or 48 hours P22077 treatment significantly reduced the viability of Huh7 and SK-Hep1 cells and induced cell death. PMC6986148
SK-Hep1 cells 10 µM or 20 µM 24 hours or 48 hours P22077 treatment significantly reduced the viability of Huh7 and SK-Hep1 cells and induced cell death. PMC6986148
SμMC-7721 cells 10 µM or 20 µM 24 hours P22077 treatment had minimal effect on the viability of SμMC-7721 cells and did not significantly induce cell death. PMC6986148
HepG2 cells 10 µM or 20 µM 24 hours P22077 treatment had minimal effect on the viability of HepG2 cells and did not significantly induce cell death. PMC6986148
HeLa 10 µM 1 h or 2 h To investigate the effect of P22077 on HSF1 phosphorylation in HeLa cells, results showed that P22077 induced HSF1 phosphorylation PMC10932104
H1299 10 µM 1 h or 2 h To investigate the effect of P22077 on HSF1 phosphorylation in H1299 cells, results showed that P22077 induced HSF1 phosphorylation PMC10932104
HEK293 10 µM 1 h or 2 h To investigate the effect of P22077 on HSF1 phosphorylation in HEK293 cells, results showed that P22077 induced HSF1 phosphorylation PMC10932104
Hep3B 10 µM 1 h or 2 h To investigate the effect of P22077 on HSF1 phosphorylation in Hep3B cells, results showed that P22077 induced HSF1 phosphorylation PMC10932104
HEK293T cells 100 nM 12 hours P22077 significantly up-regulated ubiquitination levels of Myc-SOCS1 and down-regulated SOCS1 protein expression, promoting IFN-I signaling activation. PMC7011631
A549 cells 100 nM 12 hours P22077 significantly down-regulated endogenous SOCS1 protein expression, which depended on proteasome-dependent degradation. PMC7011631
NCI-H460TXR cells 17.6 µM 48 hours Combination treatment with P22077 and volasertib significantly reduced MDR1/ABCB1 expression PMC7697005
HCAECs 10 ng/mL 36 hours USP7 inhibition significantly reduced the migration rate and permeability of HCAECs and alleviated TGF β2-induced endothelial-mesenchymal transition (EndoMT). PMC11799894
cardiomyocytes 100 nM 24 hours To evaluate the effect of P22077 on Ang II-induced cardiomyocyte hypertrophy, results showed that P22077 significantly reduced Ang II-induced cardiomyocyte hypertrophy PMC9640964

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
mice B-NDG mouse model intraperitoneal injection AZD1208: 30 mg/kg, quizartinib: 1 mg/kg Daily, tumor growth was monitored To evaluate the therapeutic effect of P22077 on the CML mouse model, results showed that P22077 significantly prolonged the survival of mice. PMC7782553
nude mice orthotopic neuroblastoma model intraperitoneal injection 15, 20, or 30 mg/kg Single dose P22077 significantly inhibits neuroblastoma growth in the mouse model PMC3920959
nude mice SK-Hep1 xenograft model intraperitoneal injection 10 and 20 mg/kg twice weekly for approximately 2 weeks P22077 significantly inhibited the tumor growth in the SK-Hep1 xenograft model. PMC6986148
Mice CAWS-induced Kawasaki disease model Intraperitoneal injection 5 mg/kg Single injection, lasting 30 minutes P22077 significantly alleviated CAWS-induced cardiac inflammation, endothelial-mesenchymal transition (EndoMT), and fibrosis in the Kawasaki disease model mice. PMC11799894
mice Ang II-induced hypertensive model intraperitoneal injection 50 mg/kg Daily for 2 weeks To evaluate the effect of P22077 on Ang II-induced cardiac hypertrophy and remodeling, results showed that P22077 significantly alleviated cardiac hypertrophy, fibrosis, inflammation, and oxidative stress PMC9640964

Protocol

Bio Calculators
Preparing Stock Solutions 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

References

[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.

 

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