Research progress of KRAS inhibitors

LI Xueyan; CHEN Na; JIANG Cheng

doi:10.11665/j.issn.1000-5048.2024010801

Journal of China Pharmaceutical University > 2024 > 55(2): 257-269. > DOI: 10.11665/j.issn.1000-5048.2024010801

LI Xueyan, CHEN Na, JIANG Cheng. Research progress of KRAS inhibitors[J]. J China Pharm Univ, 2024, 55(2): 257 − 269. DOI: 10.11665/j.issn.1000-5048.2024010801

Citation:

LI Xueyan, CHEN Na, JIANG Cheng. Research progress of KRAS inhibitors[J]. J China Pharm Univ, 2024, 55(2): 257 − 269. DOI: 10.11665/j.issn.1000-5048.2024010801

Citation:

LI Xueyan, CHEN Na, JIANG Cheng. Research progress of KRAS inhibitors[J]. J China Pharm Univ, 2024, 55(2): 257 − 269. DOI: 10.11665/j.issn.1000-5048.2024010801

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Research progress of KRAS inhibitors

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China

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Received Date: January 07, 2024

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Abstract

Abstract

KRAS protein, a small GTPase encoded by the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene, is involved in cell proliferation, differentiation, migration and cell survival, and is known as a regulatory switch for the cell life cycle. However, KRAS gene is prone to mutation, leading to hyperactivation of its downstream signaling pathways, and has a vital role in driving tumorigenesis. KRAS mutations predominantly take place at residue G12, G13 or Q61, and different mutants have varying effects on protein physiological functions and tumor types. Due to its smooth surface and high affinity for nucleotides, KRAS had been considered to be “undruggable” until the launch of selective KRAS G12C inhibitors sotorasib and adagrasib, which broke the dogma. This review introduces the structure and functions of KRAS, as well as the status and progress of inhibitors directly targeting KRAS mutants (G12C, G12D, G12R, G12S) and pan-KRAS inhibitors, aiming to provide some insightful reference for the development of KRAS inhibitors.
- RAS,
- KRAS,
- KRAS inhibitors,
- antitumor

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References (67)

References

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