YU238259

SKU: orb1302938

Description

YU238259 is a selective small molecule inhibitor of homology-directed repair (HDR) that spares non-homologous end joining (NHEJ), as demonstrated in cellular GFP reporter assays. This tool compound is useful for studying DNA repair pathway choice, synthetic lethality, and radiosensitization in both in vitro and in vivo cancer research models.

Research Area

Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 1943733-16-1
• MW: 459.95
• Purity: 99.12% (May vary between batches)
• Formula: C₂₂H₂₂ClN₃O₄S
• SMILES: COc1ccc(cc1)S(=O)(=O)NCc1ccc(cc1)C(=O)NCCc1ccc(Cl)cn1
• Target: DNA-PK
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:84 mg/mL (182.63 mM);10% DMSO+90% Corn Oil:3.3 mg/mL (7.17 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• In Vivo:
  Growth of BRCA2-deficient human tumor xenografts in nude mice is significantly delayed by YU238259 treatment even without concomitant DNA-damaging therapy.
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• In Vitro:
  YU238259 sensitizes tumor cells to radiation therapy and DSB-inducing chemotherapy. Treatment with YU238259 is not only synergistic with ionizing radiation (IR), etoposide, and PARP inhibition, but this synergism is heightened by BRCA2-deficiency. Synthetic lethality of YU238259 in HDR-deficient cells results from accumulation of unresolved DSBs following additional inhibition of residual HDR pathway activity. Inhibition of HDR activity by YU238259 has little to no effect on the NHEJ pathway.
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• Cell Research:
  U2OS cells were pretreated with 25 μM YU238259 or DMSO vehicle for 1 h and cells were then irradiated with 10 Gy IR. Cells were fixed at 8 h post-IR, stained with antibodies and Hoechst dye, and imaged. Foci were quantified using the InCell Analyzer algorithm developed by YCMD. Cells were scored as foci-positive if they contained ≥15 foci (BRCA1, pDNA-PK) or ≥20 foci (53BP1).
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• Animal Research:
  Animal Models: 069(nu)/070(nu/+) athymic nude mice. Formulation: 3:1 DMSO:PBS. Dosages: 3 mg/kg . Administration: i.p

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, HDR, DNAPK, DNA-PK, DNA-dependent protein kinase, YU 238259, YU238259, YU-238259

Compound Identifiers

PubChem CID

121473004