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ML323

Cat. No. M3721
ML323 Structure
Size Price Availability Quantity
5mg USD 63  USD63 In stock
10mg USD 100  USD100 In stock
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Quality Control & Documentation
Biological Activity

Ml-323 is a potent reversible INHIBITOR of USP1-UAF1, with an IC50 of 76 nM in UB-RHO assay.

Protocol (for reference only)
Cell Experiment
Cell lines H596 cells
Preparation method For the colony-forming assay, seeding cells at a density of 300–500 cells per well in six-well plates and growing overnight.Then treating cells with ML323 alone, cisplatin alone or a combination of cisplatin and ML323 (1:1 or 1:4) at the indicated concentrations. Treating cells with an equal volume of DMSO and usinf saline as control. After 48 h of treatment, adding fresh growth medium, and incubating cells for an additional 5-10 d to allow for colony formation. For UV combination treatment, treating the cells with ML323 at the indicated concentrations or an equal volume of DMSO. After 48 h, removing the medium , and irradiating cells at 254 nm at the indicated dosage. Adding fresh growth medium , and incubating the cells for an additional 5-10 d to allow for colony formation. The cells without UV irradiation but treated with ML323 or an equal volume of DMSO are used as controls and designated as 100%. After the formation of the colonies, fixing cells with methanol and stained with 0.5% crystal violet. Colonies consisting of >50 cells are scored. The number of colonies is determined from triplicate plates. The dose-response curves are generated using GraphPad Prism and analyzed by using CalcuSyn to calculate the combination index, which is determined for the fraction of cells affected after the addition of fixed ratios of cisplatin and the USP1-UAF1 inhibitor.
Concentrations ~30 μM
Incubation time 7-12 days
Animal Experiment
Animal models
Formulation
Dosages
Administration
Chemical Information
Molecular Weight 384.48
Formula C23H24N6
CAS Number 1572414-83-5
Solubility (25°C) DMSO
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
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.

References

[1] Dexheimer TS, et al. J Med Chem. Synthesis and Structure-Activity Relationship Studies of N-Benzyl-2-phenylpyrimidin-4-amine Derivatives as Potent USP1/UAF1 Deubiquitinase Inhibitors with Anticancer Activity against Nonsmall Cell Lung Cancer.

[2] Liang Q, et al. Nat Chem Biol. A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses.

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