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YU238259

Cat. No. M6205
YU238259 Structure
Size Price Availability Quantity
5mg USD 110  USD110 In stock
10mg USD 190  USD190 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

In vitro: YU238259 exhibits potent synthetic lethality in the setting of DNA damage response and DNA repair defects. 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. YU238259 sensitizes tumor cells to radiation therapy and DSB-inducing chemotherapy.

In vivo: Growth of BRCA2-deficient human tumor xenografts in nude mice is significantly delayed by YU238259 treatment even in the absence of concomitant DNA-damaging therapy.

Protocol
Cell Experiment
Cell lines U2OS cells
Preparation method 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).
Concentrations 25 μM
Incubation time 1 h
Animal Experiment
Animal models 069(nu)/070(nu/+) athymic nude mice
Formulation 3:1 DMSO:PBS
Dosages 3 mg/kg
Administration i.p.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 459.95
Formula C22H22ClN3O4S
CAS Number 1943733-16-1
Purity >98%
Solubility 91 mg/mL in DMSO
Storage at -20°C
References

[1] Stachelek GC, et al. Mol Cancer Res. YU238259 Is a Novel Inhibitor of Homology-Dependent DNA Repair That Exhibits Synthetic Lethality and Radiosensitization in Repair-Deficient Tumors.

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