K-Ras(G12C) inhibitor 6
Names
Preferred IUPAC name
N-{1-[(2,4-Dichlorophenoxy)acetyl]piperidin-4-yl}-4-sulfanylbutanamide
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C17H22Cl2N2O3S/c18-12-3-4-15(14(19)10-12)24-11-17(23)21-7-5-13(6-8-21)20-16(22)2-1-9-25/h3-4,10,13,25H,1-2,5-9,11H2,(H,20,22)
    Key: ZPXCEHMKUTXHRZ-UHFFFAOYSA-N
  • SCCCC(=O)NC1CCN(CC1)C(=O)COC1=CC=C(Cl)C=C1Cl
Properties
C17H22Cl2N2O3S
Molar mass 405.33 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

K-Ras(G12C) inhibitor 6 is an irreversible inhibitor of oncogenic K-Ras(G12C),[1] subverting the native nucleotide preference to favour GDP over GTP. Its family of inhibitors allosterically control GTP affinity and effector interactions by fitting inside a "pocket", or binding site, of mutant K-Ras. It is the most frequently mutated oncogene.[2]

Investigators and pathologists previously thought that K-Ras is undruggable.[3] However, Kevan M. Shokat and his colleagues, in the Howard Hughes Medical Institute (HHMI) at the University of California, recently reported a novel discovery of "Achilles heel" on K-RAs, and believed that it has real translational implications for patients with K-RAs mutation.

In recent years, significant research efforts have focused on finding effective inhibitors for the Kras-G12C mutation. For instance, sotorasib (Lumakras) became the first FDA-approved targeted therapy for the treatment of patients with NSCLC harboring the Kras-G12C mutation in 2021.[4] Adagrasib (MRTX849) is another inhibitor that has shown promising results in clinical trials.[5]

References

  1. ↑ "K-Ras(G12C) inhibitor 6". selleckchem.com.
  2. ↑ "Targeting KRAS-G12C | Amgen Oncology". www.amgenoncology.com. Retrieved 2023-12-09.
  3. ↑ "Researchers identify new mechanism to target 'undruggable' cancer gene". www.sciencedaily.com. Retrieved 2017-01-17.
  4. ↑ "Sotorasib is First KRAS Inhibitor Approved by FDA - NCI". www.cancer.gov. 2021-06-25. Retrieved 2023-12-09.
  5. ↑ Dhillon, Sohita (February 2023). "Adagrasib: First Approval". Drugs. 83 (3): 275–285. doi:10.1007/s40265-023-01839-y. ISSN 1179-1950. PMID 36763320.
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