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  • Title: Recent advances in the rational design and development of LIM kinase inhibitors are not enough to enter clinical trials.
    Author: Manetti F.
    Journal: Eur J Med Chem; 2018 Jul 15; 155():445-458. PubMed ID: 29908439.
    Abstract:
    LIM kinases are involved in various pathophysiological processes that depend on actin organization. Alteration of microtubule dynamics by LIMK dysregulation is in fact related to tumor progression and metastasis, viral infection, and ocular diseases, such as glaucoma. As a consequence, many efforts have been done in recent years to rationally design small molecules able to inhibit LIMK activity selectively, without affecting other kinases. As a result, compounds optimized in terms of binding affinity and pharmacokinetic parameters have been discovered, that however failed to access clinical trials. In this review, a comprehensive survey of recent LIMK inhibitors is reported, together with SAR considerations and optimization processes.
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