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. Author manuscript; available in PMC: 2024 Nov 3.
Published in final edited form as: Cell. 2024 Sep 9;187(22):6379–6392.e17. doi: 10.1016/j.cell.2024.08.017

Figure 4. Cellular targeting of Ras-family GTPases with RMC6291.

Figure 4.

(A) X-ray structure of tricomplex of RMC-4998, K-Ras(G12C), and CypA (PDB: 8G9P). K-Ras residues involved in binding RMC-4998 are colored in blue. Negatively charged K-Ras residues involved in binding CypA are colored in orange.

(B) Sequence alignment of Ras-family GTPases K-Ras, M-Ras, R-Ras, and Rheb. Residues mediating drug resistance to RMC-4998 are highlighted in light orange (mild effect) and orange (strong effect).

(C) Immunoblot of HeLa cells transiently overexpressing K-Ras or K-Ras(G12C). HeLa cells were transiently transfected, treated with different concentration ofRMC-6291 for 3 h, and blotted for Ras.

(D) Immunoblot of HeLa cells transiently overexpressing M-Ras or M-Ras(G22C). HeLa cells were transiently transfected, treated with different concentration ofRMC-6291 for 3 h, and blotted for M-Ras.

(E) Immunoblot of HeLa cells transiently overexpressing R-Ras1 or R-Ras1(G38C). HeLa cells were transiently transfected, treated with different concentration ofRMC-6291 for 3 h, and blotted for R-Ras.

(F) Immunoblot of HeLa cells transiently overexpressing Rheb or Rheb(R15C). HeLa cells were transiently transfected, treated with different concentration of RMC-6291 for 3 h, and blotted for Rheb. Data are representative of three independent experiments.