What question did this study set out to answer?

To characterize the in vitro selectivity, biochemical profile, and in vivo antitumor efficacy of masitinib (AB1010), a novel tyrosine kinase inhibitor targeting KIT.

September 29, 2009PLoS ONEOpen Access

Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

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To characterize the in vitro selectivity, biochemical profile, and in vivo antitumor efficacy of masitinib (AB1010), a novel tyrosine kinase inhibitor targeting KIT.
Assayed recombinant human wild-type KIT, PDGFR, Lyn, FGFR3, ABL, and diverse serine/threonine kinases to evaluate enzyme selectivity and binding kinetics.
Measured stem cell factor-induced proliferation, KIT phosphorylation, degranulation, cytokine production, and migration in wild-type and mutant KIT-expressing Ba/F3 and mast cells.
Evaluated in vivo oral bioavailability, toxicity, and tumor suppression in mice subcutaneously grafted with Ba/F3 cells harboring juxtamembrane KIT mutations.
Masitinib inhibited recombinant human wild-type KIT with an IC50 of 200 +/- 40 nM and blocked factor-dependent Ba/F3 cell proliferation and phosphorylation with an IC50 of 150 +/- 80 nM.
The compound potently targeted PDGFR and Lyn but exhibited weak inhibition of ABL and c-Fms, demonstrating greater suppression of mast cell degranulation and cytokine production than imatinib.
Masitinib blocked juxtamembrane KIT mutant tumor growth in grafted mice and demonstrated oral bioavailability without causing cardiotoxicity or genotoxicity in animal models.

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Implication

Preclinical study demonstrates potent and selective KIT inhibition by masitinib in cell and mouse models, suggesting improved efficacy and safety over imatinib.

Cite This Study

Dubreuil et al. (2009) studied this question.

synapsesocial.com/papers/6a17ffc5cf49e78c48b4b1fb https://doi.org/10.1371/journal.pone.0007258

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Implication

Preclinical study demonstrates potent and selective KIT inhibition by masitinib in cell and mouse models, suggesting improved efficacy and safety over imatinib.

Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

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Discussion

Implication

Cite This Study

Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

Key Points

Discussion

Implication

Cite This Study

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