KU-0058948
Based on 1 Customer Validation
KU-0058948 is a potent PARP1 inhibitor with an IC50 of 3.4 nM. KU-0058948 induces the accumulation of DNA double-strand breaks through inhibition of PARP1, triggering chromosomal aberrations, cell cycle arrest, and apoptosis in homologous recombination-deficient cells, while impeding the recruitment of the NuRD/PcG complex to affect chromatin remodeling. KU-0058948 can be used for research on cancers such as myeloid leukemia.
For research use only. We do not sell to patients.
- Purity : 99.79%
- CAS No.: 763111-49-5
- Formula: C21H21FN4O2
- Molecular Weight:380.42
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
PARP-1 3.4 nM (IC50) |
In Vitro
KU-0058948 (1 μM; 24 h) significantly increases γH2AX phosphorylation foci and reduces rad51 foci formation in sensitive leukemia cell lines (P39, Mutz-3) and primary AML cells, thereby confirming the presence of homologous recombination deficiency in these cells[2].
KU-0058948 (5-10 nM; 5-14 days) does not enhance the cytotoxicity of the DNA methyltransferase inhibitor (5'-aza-2'-CdR) (HY-A0004) in AML primary cells and leukemia cell lines (P39, HL60, Mutz-3), but produces a strong synergistic effect with the histone deacetylase (HDAC) inhibitor MS275 (HY-12163), significantly enhancing the cytotoxicity of MS275[2].
KU-0058948 (100 μM; 24 h) in P39 and Mutz-3 cells, when combined with 100 nM MS275 exposure, extremely significantly increases γH2AX phosphorylation focus formation compared with the product alone[2].
KU-0058948 (10 µM; 3 h) inhibits local UV-induced loss of GFP-H1 and GFP-H4 in damaged U2OS cells[3].
KU-0058948 (1 μM; 4-16 h) significantly inhibits the large-scale chromatin decondensation induced by tethered DDB2 in human U2OS 2-6-3 cells containing a LacO array[3].
KU-0058948 (10 µM; 3 h) significantly inhibits the recruitment of the repair protein XPC to UV-induced DNA damage sites and limits its immobilization on chromatin in human U2OS cells and XP4PA cells[3].
KU-0058948 (1 μM; 1 h before UV laser microirradiation) abolishes the recruitment of MEL-18 to UV laser-induced DNA damage sites in HeLa cells[4].
KU-0058948 inhibits the recruitment of MTA1 and CHD4 to UV laser-induced DNA damage sites in cells[4].
KU-0058948 (1 h before UV laser microirradiation) reverses the manifestation of PARG siRNA-induced m7G cap and RNAP2-ser2 resistance stripes at UV laser microirradiation sites in HeLa cells, indicating that PARP activity is required for transcriptional repression at DNA damage sites[4].
KU-0058948 (1 µM; 1 h) inhibits PARP1 poly (ADP-ribosyl) ation but does not alter the kinetics of Menadione (HY-B1897A)-induced global CSB-chromatin binding in CS1AN-CSBWT cells[5].
KU-0058948 (1 µM; 1 h) reduces Menadione-induced CSB occupancy at chrX-1 and chrX-2 in CS1AN-CSBWT cells, but does not affect chr17-1 or chr19-2[5].
KU-0058948 (1 µM; 24 h) increases NHEJ end-joining efficiency and error-prone repair frequency in fibroblast nuclear extracts, with BLM−/− error-prone repair rising from 8.7% to 15.9%[6].
KU-0058948 (10 pM-10 µM; 12-14 days) reduces clonogenic survival of chromosomally unstable fibroblasts, with BRCA2−/− cells exhibiting 10-fold greater sensitivity than ATM−/− and NBS1−/− cells[6].
KU-0058948 (1 µM; 24 h) eliminates Rad51 foci in BRCA2−/−, ATM−/−, and NBS1−/− fibroblasts but does not affect BLM−/− or DNL IV−/− fibroblasts[6].
KU-0058948 (0.1-10 μM; 7-10 days) reduces clonogenic survival to a greater extent in Brca1S971A/S971A MEFs than in Brca1C/C MEFs in the p53−/− background, indicating moderate PARP inhibitor hypersensitivity[7].
KU-0058948 potently and completely blocks PARP enzyme activity in purified HDAC enzyme and recombinant human PARP enzyme reaction systems but has no direct inhibitory effect on HDAC enzyme activity[2].
KU-0058948 (10 μM; 30 min) inhibits recombinant H. aurantiacus PARP self-modification in a DNA-dependent cell-free assay[8].
KU-0058948 (2-20 min after microirradiation) does not alter the relocalization of PARP3 to laser-induced DNA damage sites in Cos1 cells[9].
KU-0058948 eliminates PARP3-stimulated tankyrase 1 auto-ADP-ribosylation and NuMA hetero-ADP-ribosylation in in vitro assays[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:P39 and HL60 leukemic cell lines
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Concentration:1 μM
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Incubation Time:48, 72， 120 h
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Result:Caused an accumulation of cells in the S phase and an increase in the G2/M population.
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Cell Line:P39 cells
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Concentration:1 μM
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Incubation Time:24， 48, 72， 120 h
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Result:Induced profound levels of apoptosis specifically in the repair-defective P39 cells, as confirmed by Annexin V staining and sub-G1 peak analysis at 120 h.
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Cell Line:P39, Mutz-3 and primary AML patient cells
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Concentration:1 μM, 100 μM
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Incubation Time:24 h
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Result:Induced significantly increased γH2AX phosphorylation foci in sensitive leukemic cells while failing to elicit Rad51 foci formation, confirming that the target cells lack an effective homologous recombination DNA repair pathway.
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Cell Line:HeLa cells
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Concentration:1 μM
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Incubation Time:1 h before UV laser microirradiation
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Result:Control cells efficiently recruited MEL-18 to DNA lesions.
MEL-18 recruitment was largely abrogated, while γH2AX stripes remained detectable at DNA damage sites.
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Cell Line:CS1AN-CSBWT cells (CS1AN-sv cells stably expressing wild-type CSB)
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Concentration:1 µM
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Incubation Time:1 h
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Result:Decreased poly(ADP-ribosyl)ation activity was observed by anti-PAR Western blot.
The kinetics of menadione-induced global CSB-chromatin association were not significantly changed; percent CSB co-fractionating with chromatin was similar to DMSO control across the indicated times.
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Cell Line:CS1AN-CSBWT cells
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Concentration:1 µM
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Incubation Time:1 h
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Result:CSB occupancy was significantly decreased at chrX-1 and chrX-2, but not at chr17-1 or chr19-2.
Chemical Information
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CAS No. 763111-49-5
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Appearance Solid
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Molecular Weight 380.42
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Formula C21H21FN4O2
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Color White to off-white
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SMILES
O=C1NN=C(CC2=CC=C(F)C(C(N3CCNCCC3)=O)=C2)C4=C1C=CC=C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 16.67 mg/mL (43.82 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (298 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Farmer H, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 Apr 14;434(7035):917-21. [Content Brief]
[2]. Gaymes TJ, et al. Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes. Haematologica. 2009 May;94(5):638-46. [Content Brief]
[8]. Slade D, et al. The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase. Nature. 2011 Sep 04;477(7366):616-20. [Content Brief]
[9]. Boehler C, et al. Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. Proceedings of the National Academy of Sciences of the United States of America. 2011 Feb 15;108(7):2783-8. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6287 mL | 13.1434 mL | 26.2867 mL | 65.7168 mL |
| 5 mM | 0.5257 mL | 2.6287 mL | 5.2573 mL | 13.1434 mL | |
| 10 mM | 0.2629 mL | 1.3143 mL | 2.6287 mL | 6.5717 mL | |
| 15 mM | 0.1752 mL | 0.8762 mL | 1.7524 mL | 4.3811 mL | |
| 20 mM | 0.1314 mL | 0.6572 mL | 1.3143 mL | 3.2858 mL | |
| 25 mM | 0.1051 mL | 0.5257 mL | 1.0515 mL | 2.6287 mL | |
| 30 mM | 0.0876 mL | 0.4381 mL | 0.8762 mL | 2.1906 mL | |
| 40 mM | 0.0657 mL | 0.3286 mL | 0.6572 mL | 1.6429 mL |
KU-0058948 Related Classifications
HY-136489 Related Classifications
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