P22077 | CAS#1247819-59-5 | USP7 inhibitor

MedKoo Cat#: 406569 | Name: P22077

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

P22077

CAS#1247819-59-5

Theoretical Analysis

MedKoo Cat#: 406569

Name: P22077

CAS#: 1247819-59-5

Chemical Formula: C12H7F2NO3S2

Exact Mass: 314.9835

Molecular Weight: 315.31

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
25mg	USD 250.00	2 Weeks
50mg	USD 350.00	2 Weeks
100mg	USD 550.00	2 Weeks
200mg	USD 750.00	2 Weeks
500mg	USD 1,250.00	2 Weeks
1g	USD 2,250.00	2 Weeks
2g	USD 3,650.00	2 Weeks

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Related CAS #

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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

Product Data

Instruction

View handling instruction

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/

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

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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.

1: Zeng D, Zhang W, Chen X, Ou G, Huang Y, Yu C. Inhibitory Effect of P22077 on Airway Inflammation in Rats with COPD and Its Mechanism. Int J Chron Obstruct Pulmon Dis. 2024 Mar 20;19:779-788. doi: 10.2147/COPD.S451244. PMID: 38529479; PMCID: PMC10962660. 2: Lim CH, Fang XQ, Kang H, Oh T, Lee S, Kim YS, Lim JH. ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway. Int J Mol Sci. 2024 Feb 27;25(5):2768. doi: 10.3390/ijms25052768. PMID: 38474017; PMCID: PMC10932104. 3: Wang Y, Gu YH, Ren KW, Xie X, Wang SH, Zhu XX, Wang L, Yang XL, Bi HL. Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice. Hypertens Res. 2024 May;47(5):1309-1322. doi: 10.1038/s41440-024-01581-2. Epub 2024 Feb 19. PMID: 38374239. 4: Hu M, Dai C, Sun X, Chen Y, Xu N, Lin Z, Xu S, Cheng C, Tan Z, Bian S, Zheng W. Ubiquitination-specific protease 7 enhances stemness of hepatocellular carcinoma by stabilizing basic transcription factor 3. Funct Integr Genomics. 2024 Feb 10;24(1):28. doi: 10.1007/s10142-024-01310-5. PMID: 38340226. 5: Zhang X, Feng N, Wu B, Guo Z, Pan T, Tao X, Zheng H, Zhang W. Prognostic value and immune landscapes of cuproptosis-related lncRNAs in esophageal squamous cell carcinoma. Aging (Albany NY). 2023 Oct 6;15(19):10473-10500. doi: 10.18632/aging.205089. Epub 2023 Oct 6. PMID: 37812189; PMCID: PMC10599721. 6: 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. 7: Wu Y, Gu H, Bao Y, Lin T, Wang Z, Gu D, Shen H, Xian H, Fan Y, Mao R. USP7 sustains an active epigenetic program via stabilizing MLL2 and WDR5 in diffuse large B-cell lymphoma. Cell Biochem Funct. 2022 Jun;40(4):379-390. doi: 10.1002/cbf.3702. Epub 2022 Apr 12. PMID: 35411950. 8: Bian S, Ni W, Zhu M, Zhang X, Qiang Y, Zhang J, Ni Z, Shen Y, Qiu S, Song Q, Xiao M, Zheng W. Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation. Int J Biol Sci. 2022 Jan 1;18(3):1022-1038. doi: 10.7150/ijbs.68179. PMID: 35173534; PMCID: PMC8771828. 9: 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. 10: Lei H, Xu HZ, Shan HZ, Liu M, Lu Y, Fang ZX, Jin J, Jing B, Xiao XH, Gao SM, Gao FH, Xia L, Yang L, Liu LG, Wang WW, Liu CX, Tong Y, Wu YZ, Zheng JK, Chen GQ, Zhou L, Wu YL. Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia. Nat Commun. 2021 Jan 4;12(1):51. doi: 10.1038/s41467-020-20259-0. PMID: 33397955; PMCID: PMC7782553. 11: Shin SB, Kim CH, Jang HR, Yim H. Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance. Int J Mol Sci. 2020 Nov 16;21(22):8629. doi: 10.3390/ijms21228629. PMID: 33207738; PMCID: PMC7697005. 12: 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. 13: Chen H, Zhu X, Sun R, Ma P, Zhang E, Wang Z, Fan Y, Zhou G, Mao R. Ubiquitin-specific protease 7 is a druggable target that is essential for pancreatic cancer growth and chemoresistance. Invest New Drugs. 2020 Dec;38(6):1707-1716. doi: 10.1007/s10637-020-00951-0. Epub 2020 May 28. PMID: 32468271. 14: Deng J, Liang L, Yi H, Su T, Yang Z, Nie L, Liu J. USP7 inhibition inhibits proliferation and induces megakaryocytic differentiation in MDS cells by upregulating gelsolin. Br J Haematol. 2020 Aug;190(3):418-429. doi: 10.1111/bjh.16549. Epub 2020 Mar 4. PMID: 32130729. 15: He Y, Li W, Lv D, Zhang X, Zhang X, Ortiz YT, Budamagunta V, Campisi J, Zheng G, Zhou D. Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity. Aging Cell. 2020 Mar;19(3):e13117. doi: 10.1111/acel.13117. Epub 2020 Feb 16. PMID: 32064756; PMCID: PMC7059172. 16: Zhang W, Zhang J, Xu C, Zhang S, Bian S, Jiang F, Ni W, Qu L, Lu C, Ni R, Fan Y, Xiao M, Liu J. Ubiquitin-specific protease 7 is a drug-able target that promotes hepatocellular carcinoma and chemoresistance. Cancer Cell Int. 2020 Jan 28;20:28. doi: 10.1186/s12935-020-1109-2. PMID: 32002017; PMCID: PMC6986148. 17: Yuan Y, Miao Y, Zeng C, Liu J, Chen X, Qian L, Wang X, Qian F, Yu Z, Wang J, Qian G, Fu Q, Lv H, Zheng H. Small-molecule inhibitors of ubiquitin-specific protease 7 enhance type-I interferon antiviral efficacy by destabilizing SOCS1. Immunology. 2020 Mar;159(3):309-321. doi: 10.1111/imm.13147. Epub 2019 Dec 5. PMID: 31691271; PMCID: PMC7011631. 18: Lamberto I, Liu X, Seo HS, Schauer NJ, Iacob RE, Hu W, Das D, Mikhailova T, Weisberg EL, Engen JR, Anderson KC, Chauhan D, Dhe-Paganon S, Buhrlage SJ. Structure-Guided Development of a Potent and Selective Non-covalent Active-Site Inhibitor of USP7. Cell Chem Biol. 2017 Dec 21;24(12):1490-1500.e11. doi: 10.1016/j.chembiol.2017.09.003. Epub 2017 Oct 19. PMID: 29056421; PMCID: PMC5749250. 19: 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. doi: 10.1016/j.chembiol.2017.09.004. Epub 2017 Oct 19. PMID: 29056420. 20: 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. doi: 10.1038/nchembio.2486. Epub 2017 Oct 2. PMID: 28967922; PMCID: PMC6314479.