K-Ras(G12C) inhibitor 6

K-Ras(G12C) inhibitor 6

Names
Preferred IUPAC name N-{1-[(2,4-Dichlorophenoxy)acetyl]piperidin-4-yl}-4-sulfanylbutanamide
Identifiers
CAS Number	2060530-16-5
3D model (JSmol)	Interactive image
ChemSpider	31042597
PubChem CID	71815954
UNII	JPV55C3PN4 Y
InChI 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
SMILES SCCCC(=O)NC1CCN(CC1)C(=O)COC1=CC=C(Cl)C=C1Cl
Properties
Chemical formula	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), 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.

Investigators and pathologists previously thought that K-Ras is undruggable. 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. Adagrasib (MRTX849) is another inhibitor that has shown promising results in clinical trials.