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A Review of the in Silico Design and Development Approaches of Ras-Specific Anticancer Therapeutics

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International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Ras Proteins, play a pivotal role in the proliferation pathways, and Ras mutant forms are well-established cancer drivers. Ras mutations are found in about 30% of all human cancers widely known as challenging diseases to control and treat. The direct inhibition of Ras is challenging and makes Ras an “undruggable” target for many years. The important reason is, that Ras protein has a unique smooth surface and shows different dynamicity upon binding GDP and GTP. As a result, interfering peptides (IPs) targeting the Ras family protein-protein interactions (PPIs) are considered more likely to bind Ras effectively and inhibit the downstream signaling. In this review, we aimed to cover the recent approaches to design the peptides that target Ras family proteins, focusing on in silico methods. In this regard, the anti-cancer peptide development approaches including design and delivery strategies are discussed. Later, more specific methods regarding Ras-specific peptide design are presented. In conclusion, IPs are a promising group of cancer therapeutics to combat Ras mutant cancers. For future perspectives to have these peptides in clinical use, co-inhibition of other cancer targets as well as improving the pharmacokinetic features of peptides are suggested.

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Funding

This manuscript is supported by the grant of the National Institute for Medical Research Development (NIMAD), with grant number 972544.

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Authors and Affiliations

  1. Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Parinaz Motiei, Hamid Reza Heidari, Mohammad Saeid Hejazi & Elnaz Mehdizadeh Aghdam

  2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Parinaz Motiei, Hamid Reza Heidari, Mohammad Saeid Hejazi, Ommoleila Molavi & Elnaz Mehdizadeh Aghdam

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  1. Parinaz Motiei
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  2. Hamid Reza Heidari
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  3. Mohammad Saeid Hejazi
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  4. Ommoleila Molavi
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  5. Elnaz Mehdizadeh Aghdam
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Contributions

All authors have made a contribution to the concept or design of the article. P.M. and H.R.H. drafted the manuscript and interpret the relevant literature. M.S.H. and O.M revised the manuscript. E.M.A. conceptualize and draft the manuscript and interpret the relevant literature.

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Correspondence to Elnaz Mehdizadeh Aghdam.

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Motiei, P., Heidari, H.R., Hejazi, M.S. et al. A Review of the in Silico Design and Development Approaches of Ras-Specific Anticancer Therapeutics. Int J Pept Res Ther 30, 2 (2024). https://doi.org/10.1007/s10989-023-10578-3

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