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PD166326

Cat. No. M8118
PD166326 Structure
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Biological Activity

PD166326 is an ATP-competitive inhibitor of BCR-ABL and Src kinases, inhibiting Src and Abl with IC50 values of 6 nM and 8 nM, respectively.

Chemical Information
Molecular Weight 427.28
Formula C21H16Cl2N4O2
CAS Number 185039-91-2
Solubility (25°C) DMSO: 2 mg/mL
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] Sbastien Grosso, et al. Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors

[2] Justyna Jakubowska, et al. Novel inhibitors of Bcr-Abl

[3] Shinya Kimura, et al. New tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

[4] Nicholas C Wolff, et al. PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia

[5] Nikolas von Bubnoff, et al. A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the mutation pattern for PD166326, an alternative Abl kinase inhibitor

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