P22077
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MedKoo CAT#: 406569

CAS#: 1247819-59-5

Description: P22077 is a potent and selective ubiquitin-specific protease 7 (USP7) inhibitor. P22077 potently induces apoptosis in NB cells with an intact USP7-HDM2-p53 axis but not in NB cells with mutant p53 or without human homolog of MDM2 (HDM2) expression. P22077 also significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) in NB cells with an intact USP7-HDM2-p53 axis. Moreover, P22077 was found to be able to sensitize chemoresistant LA-N-6 NB cells to chemotherapy. In an in vivo orthotopic NB mouse model, P22077 significantly inhibited the xenograft growth of three NB cell lines. USP7-specific inhibitors like P22077 may serve not only as a stand-alone therapy but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact USP7-HDM2-p53 axis.


Chemical Structure

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P22077
CAS# 1247819-59-5

Theoretical Analysis

MedKoo Cat#: 406569
Name: P22077
CAS#: 1247819-59-5
Chemical Formula: C12H7F2NO3S2
Exact Mass: 314.98
Molecular Weight: 315.309
Elemental Analysis: C, 45.71; H, 2.24; F, 12.05; N, 4.44; O, 15.22; S, 20.34

Price and Availability

Size Price Availability Quantity
5g USD -1
10mg USD 150
25mg USD 250
50mg USD 350
100mg USD 550
200mg USD 750
500mg USD 1250
1g USD 2250
2g USD 3650
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Synonym: P22077; P-22077; P 22077.

IUPAC/Chemical Name: 1-(5-((2,4-difluorophenyl)thio)-4-nitrothiophen-2-yl)ethanone

InChi Key: RMAMGGNACJHXHO-UHFFFAOYSA-N

InChi Code: InChI=1S/C12H7F2NO3S2/c1-6(16)11-5-9(15(17)18)12(20-11)19-10-3-2-7(13)4-8(10)14/h2-5H,1H3

SMILES Code: CC(C1=CC([N+]([O-])=O)=C(SC2=CC=C(F)C=C2F)S1)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:         

Product Data:
Biological target: P 22077 is a cell-permeable ubiquitin-specific protease 7 (USP7) inhibitor.
In vitro activity: This study found that P22077 stabilized p53 by inducing HDM2 protein degradation in NB cells. P22077 also significantly augmented the cytotoxic effects of doxorubicin (Dox) and etoposide (VP-16) in NB cells with an intact USP7-HDM2-p53 axis. Moreover, P22077 was found to be able to sensitize chemoresistant LA-N-6 NB cells to chemotherapy. Reference: Cell Death Dis. 2013 Oct 17;4(10):e867. https://pubmed.ncbi.nlm.nih.gov/24136231/
In vivo activity: These data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-β/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Reference: Front Pharmacol. 2022 Oct 25;13:1021361. https://pubmed.ncbi.nlm.nih.gov/36386139/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 43.6 138.38
DMSO:PBS (pH 7.2) (1:2) 0.3 1.05
Ethanol 0.6 1.74

Preparing Stock Solutions

The following data is based on the product molecular weight 315.31 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Xiang M, Liang L, Kuang X, Xie Z, Liu J, Zhao S, Su J, Chen X, Liu H. Pharmacological inhibition of USP7 suppresses growth and metastasis of melanoma cells in vitro and in vivo. J Cell Mol Med. 2021 Oct;25(19):9228-9240. doi: 10.1111/jcmm.16834. Epub 2021 Sep 1. PMID: 34469054; PMCID: PMC8500953. 2. 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. doi: 10.1038/cddis.2013.400. PMID: 24136231; PMCID: PMC3920959. 3. Gu YH, Ren KW, Wang Y, Wang SH, Yu XH, Xu LW, Li HH, Bi HL. Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice. Front Pharmacol. 2022 Oct 25;13:1021361. doi: 10.3389/fphar.2022.1021361. PMID: 36386139; PMCID: PMC9640964. 4. Zhao XB, Ji FY, Li HR, Zhu HH, Zhao ZZ, Ling J, Di QQ, Ma XY, Chen WL. P22077 inhibits LPS-induced inflammatory response by promoting K48-linked ubiquitination and degradation of TRAF6. Aging (Albany NY). 2020 Jun 9;12(11):10969-10982. doi: 10.18632/aging.103309. Epub 2020 Jun 9. PMID: 32516131; PMCID: PMC7346011.
In vitro protocol: 1. Xiang M, Liang L, Kuang X, Xie Z, Liu J, Zhao S, Su J, Chen X, Liu H. Pharmacological inhibition of USP7 suppresses growth and metastasis of melanoma cells in vitro and in vivo. J Cell Mol Med. 2021 Oct;25(19):9228-9240. doi: 10.1111/jcmm.16834. Epub 2021 Sep 1. PMID: 34469054; PMCID: PMC8500953. 2. 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. doi: 10.1038/cddis.2013.400. PMID: 24136231; PMCID: PMC3920959.
In vivo protocol: 1. Gu YH, Ren KW, Wang Y, Wang SH, Yu XH, Xu LW, Li HH, Bi HL. Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice. Front Pharmacol. 2022 Oct 25;13:1021361. doi: 10.3389/fphar.2022.1021361. PMID: 36386139; PMCID: PMC9640964. 2. Zhao XB, Ji FY, Li HR, Zhu HH, Zhao ZZ, Ling J, Di QQ, Ma XY, Chen WL. P22077 inhibits LPS-induced inflammatory response by promoting K48-linked ubiquitination and degradation of TRAF6. Aging (Albany NY). 2020 Jun 9;12(11):10969-10982. doi: 10.18632/aging.103309. Epub 2020 Jun 9. PMID: 32516131; PMCID: PMC7346011.

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1: 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:e867. doi: 10.1038/cddis.2013.400. PubMed PMID: 24136231; PubMed Central PMCID: PMC3920959.

2: Dar A, Shibata E, Dutta A. Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway. Mol Cell Biol. 2013 Aug;33(16):3309-20. doi: 10.1128/MCB.00358-13. Epub 2013 Jun 17. PubMed PMID: 23775119; PubMed Central PMCID: PMC3753911.

3: Altun M, Kramer HB, Willems LI, McDermott JL, Leach CA, Goldenberg SJ, Kumar KG, Konietzny R, Fischer R, Kogan E, Mackeen MM, McGouran J, Khoronenkova SV, Parsons JL, Dianov GL, Nicholson B, Kessler BM. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol. 2011 Nov 23;18(11):1401-12. doi: 10.1016/j.chembiol.2011.08.018. PubMed PMID: 22118674.