Recent Advances in Developing K-Ras Plasma Membrane Localization Inhibitors

Na       Ye; Qingfeng       Xu; Wanwan       Li; Pingyuan       Wang; Jia       Zhou
doi:10.2174/1568026619666190902145116
Abstract

The Ras proteins play an important role in cell growth, differentiation, proliferation and survival by regulating diverse signaling pathways. Oncogenic mutant K-Ras is the most frequently mutated class of Ras superfamily that is highly prevalent in many human cancers. Despite intensive efforts to combat various K-Ras-mutant-driven cancers, no effective K-Ras-specific inhibitors have yet been approved for clinical use to date. Since K-Ras proteins must be associated to the plasma membrane for their function, targeting K-Ras plasma membrane localization represents a logical and potentially tractable therapeutic approach. Here, we summarize the recent advances in the development of K-Ras plasma membrane localization inhibitors including natural product-based inhibitors achieved from high throughput screening, fragment-based drug design, virtual screening, and drug repurposing as well as hit-to-lead optimizations.
Keywords: RAS, K-Ras, K-Ras mutation, Plasma membrane localization inhibitors, Cancer, Drug discovery.
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Graphical Abstract

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DOI https://dx.doi.org/10.2174/1568026619666190902145116	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

Recent Advances in Developing K-Ras Plasma Membrane Localization Inhibitors

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