- WP1130
- LDN 57444
- P005091
- SJB3-019A
- SJB2-043
- IU1
| C527Inhibitor of USP1/USF1 complex |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.02%
- COA (Certificate Of Analysis)
- HPLC(Retest)
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- MSDS (Material Safety Data Sheet)
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Chemical structure
| Kinase experiment [1]: | |
In Vitro Deubiquitination Assays | Purified USP5 enzyme was purchased from Boston Biochem. UCH-L1 and UCH-L3 were as reported previously. USP12/46 was prepared in our laboratory as described. The in vitro enzymatic assays were performed as described previously using ubiquitin-AMC (Ub-7-amido-4methylcoumarin; Boston Biochem) as a substrate in a reaction buffer containing 20 mM HEPES-KOH (pH 7.8), 20 mM NaCl, 0.1 mg/ml ovalbumin, 0.5 mM EDTA and 10 mM dithiothreitol. The fluorescence was measured by FluoStar Galaxy Fluorometer (BMG Labtech). For the Ub-vinylsulfone (VS) assay, the proteins were incubated with Ub-VS (Boston Biochem) at 0.5 μM final concentration for 45 min at 30 °C, followed by the immunoblotting analysis. |
| Cell experiment [1]: | |
Cell lines | human U20S osteosarcoma cells, Hela cells |
Preparation method | The solubility of this compound in DMSO is <2.93mg l.="" general="" tips="" for="" obtaining="" a="" higher="" concentration:="" please="" warm="" the="" tube="" at="" 37℃="" for="" 10="" minutes="" and/or="" shake="" it="" in="" the="" ultrasonic="" bath="" for="" a="" while.="" stock="" solution="" can="" be="" stored="" below="" -20℃="" for="" several=""> |
Reacting condition | 0.5, 1 and 2 μM; 24 h |
Applications | In human U20S osteosarcoma cells, C527 promoted ID1 degradation in a dose-dependent way. In Hela cells, C527 increased the levels of Ub-FANCD2 and Ub-FANCI. Pre-treatment with C527 also enhanced the cytoxicity of DNA damaging agents including Mitomyin C and Camptothecin. C527 inhibited Camptothecin induced the Rad51 foci formation and reduced homologous recombination (HR) activity. |
References: 1.Mistry H, Hsieh G, Buhrlage SJ et al. Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol Cancer Ther. 2013 Dec;12(12):2651-62. doi: 10.1158/1535-7163.MCT-13-0103-T. Epub 2013 Oct 15. | |
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| Cas No. | 192718-06-2 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | 2-(4-fluorophenyl)naphtho[2,3-d]oxazole-4,9-dione | ||
| Canonical SMILES | O=C1C2=C(N=C(C3=CC=C(F)C=C3)O2)C(C4=CC=CC=C41)=O | ||
| Formula | C17H8FNO3 | M.Wt | 293.25 |
| Solubility | <2.93mg l="" in="" dmso=""> | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
C527, also named heterocyclic tricyclic 1,4-dihydro-1,4-dioxo-1H-naphthalene, is an inhibitor of USP1 (deubiquitinating enzyme 1) / USF1 (USP1-associated factor 1) complex with IC50 value of 0.88 ± 0.03 μM in vivo. C527 is a pan-deubiquitinating enzyme inhibitor in vitro, with a high nanomolar IC50 for the USP1/UAF1 complex.C527 inhibited the DUB activity of the USP12/USP46 complex and other DUB enzymes in vitro. However, the IC50 of C527 for these DUB enzymes was higher in comparison to USP1/UAF1 complex. C527 had considerably less inhibitory effect on UCH-L1 and UCH-L3, a different subclass of deubiquitinating enzymes, referred to as the ubiquitin C- terminal hydrolases, even though they are also cysteine proteases.In several leukemic cell lines, C527 promote ID1 degradation, and cause cytotoxicity. In mouse osteosarcoma cells, C527 promotes the degradation of ID1 and the concurrent upregulation of p21. in human U20S osteosarcoma cells, C527 promoted the dose-dependent degradation of ID1. In Hela cells, C527 treatments caused an increase in the levels of Ub-FANCD2 and Ub-FANCI, and inhibited Camptothecin induced the Rad51 foci. Pre-treatment of hela cells with USP1 inhibitor caused an enhancement in the cytoxicity of Mitomycin C and Camptothecin .Reference:1.Mistry H, Hsieh G, Buhrlage SJ et al. Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol Cancer Ther. 2013 Dec;12(12):2651-62. doi: 10.1158/1535-7163.MCT-13-0103-T. Epub 2013 Oct 15.
