Benzimidazole is a common kinase inhibitor scaffold and benzimidazole-based compounds interact with enzymes by multiple binding modes. In some cases, the benzimidazole acts as part of the hinge-binding motif, in others it has a scaffolding role without evidence for direct hinge binding. Several of these compounds are ATP-competitive inhibitors and show high selectivity by exploiting unique structural properties that distinguish one kinase from the majority of other kinases. However, the high specificity for a single target is not always sufficient. Thus another approach, called multi-target therapy, has been developed over the last few years. The simultaneous inhibition of various kinases may be useful because the disease is attacked at several relevant targets. Moreover, if a kinase becomes drug-resistant, a multitargeted drug can act on the other kinases. Some benzimidazole derivatives are multi-target inhibitors. In this article benzimidazole inhibitors are reported with their mechanisms of action, structure-activity relationship (SAR) and biological properties.

Benzimidazole derivatives as kinase inhibitors / Garuti L; Roberti M; Bottegoni G.. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - ELETTRONICO. - 21:20(2014), pp. 2284-2298. [10.2174/0929867321666140217105714]

Benzimidazole derivatives as kinase inhibitors

GARUTI, LAURA;ROBERTI, MARINELLA;BOTTEGONI, GIOVANNI
2014

Abstract

Benzimidazole is a common kinase inhibitor scaffold and benzimidazole-based compounds interact with enzymes by multiple binding modes. In some cases, the benzimidazole acts as part of the hinge-binding motif, in others it has a scaffolding role without evidence for direct hinge binding. Several of these compounds are ATP-competitive inhibitors and show high selectivity by exploiting unique structural properties that distinguish one kinase from the majority of other kinases. However, the high specificity for a single target is not always sufficient. Thus another approach, called multi-target therapy, has been developed over the last few years. The simultaneous inhibition of various kinases may be useful because the disease is attacked at several relevant targets. Moreover, if a kinase becomes drug-resistant, a multitargeted drug can act on the other kinases. Some benzimidazole derivatives are multi-target inhibitors. In this article benzimidazole inhibitors are reported with their mechanisms of action, structure-activity relationship (SAR) and biological properties.
2014
Benzimidazole derivatives as kinase inhibitors / Garuti L; Roberti M; Bottegoni G.. - In: CURRENT MEDICINAL CHEMISTRY. - ISSN 0929-8673. - ELETTRONICO. - 21:20(2014), pp. 2284-2298. [10.2174/0929867321666140217105714]
Garuti L; Roberti M; Bottegoni G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/289326
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