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Development of soft calineurin inhibitors for atopic dermatitis reported


To utilize the activity of calcineurin inhibitors in treating atopic dermatitis while avoiding the cancer risk related to systemic exposure of these agents, investigators at Array BioPharma have developed a series of "soft" calcineurin inhibitors. Soft drugs retain their activity on local delivery but are rapidly inactivated via metabolic pathways upon systemic exposure. Safety is enhanced as exposure of active drug to distal organs is minimized. The discovery process at Array involved the identification of inactive analogues of ciclosporin and FK-506, evaluation of the mechanism of inactivity and modification of the inactive analogues to restore bioactivity. This led to the identification of compounds which were potent in cellular and enzyme systems but ...

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