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Differential Toxicities of Kinase Inhibitors (KI) on Bone Marrow Progenitors from Different Species
Poster Title: Differential Toxicities of Kinase Inhibitors (KI) on Bone Marrow Progenitors from Different Species
Submitted on 20 Dec 2013
Author(s): Clarke, E. and Dos Santos, G.
Affiliations: Reachbio
Poster Views: 855
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Poster Information
Abstract: Kinase inhibitors(KIs) represent a new class of rationally designed drugs.

The success of Imatinib, targeting the ABL tyrosine kinase in CML, has prompted the development of other KIs for the treatment of various cancers and inflammation. Although more successful than conventional therapies, my elotoxicity is of ten a major side effect of KIs.

We previously showed that there was a direct correlation (R2= 0.81) between the in vitro human CFU-GM IC 50 values for various KIs and clinical neutropenia. Interestingly, studies have revealed significant differences between human, dog, rat and mouse CFU-GM sensitivities to certain pharmaceuticals. Since multiple animal models are of ten used in toxicity testing, we have now compared the IC50 values between human, non-human primate, dog, rat and mouse for Imatinib, Erlotinib, Dasatinib, Sorafenib and Sunitinib.
Summary: Myelotoxicity is often a side effect of kinase inhibitors. We reported a correlation (R2 = 0.81) between in vitro human CFU-GM IC50 values and clinical neutropenia. When these values were obtained from other species, non-human primate and dog values compared well with human data, but rat and mouse IC50 values differed significantly. This suggests rodent assays may not accurately predict toxicity to the human hematopoietic system.
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