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New perspectives in lung cancer therapy
DO-2 has been specifically modified at JNJ by the use of deuterium at a specific site to block a key metabolic liability that causes rapid conversion to a MET target kinase inactive, low solubility and toxic form. This major metabolic liability has been reported to be shared by the main competitors that requires high clinical doses to achieve efficacious exposures. A consequence of these high daily doses is the high level of inactive metabolite(s) that form that still carry off target activities that limits the ability to achieve the level of sustained active drug exposures required for optimal target inhibition to drive lasting efficacy.
Rapid metabolism by Aldehyde Oxidase (AOX) results in loss of activity
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