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New perspectives in lung cancer therapy
DO-2 overcomes metabolic liabilities as a result of blocking the primary metabolic path by judicious replacement of a metabolically labile hydrogen with a stronger bond strength deuterium atom. As a consequence, a secondary metabolic path assumes a greater role resulting in the formation of an alternative metabolite that has been found to maintain activity on the MET kinase as well as activity on an alternative kinase. This new target kinase has been reported to play a role in the ras signalling pathway involved in resistance to MET inhibitors and represents a promising new target for overcoming or delaying the emergence of resistance.
Incorporation of deuterium in DO-2 reduces metabolism at key sites
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