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. Author manuscript; available in PMC: 2021 Jan 9.
Published in final edited form as: Adv Cancer Res. 2020 Jul 9;148:69–146. doi: 10.1016/bs.acr.2020.05.002

Figure 4. RAS activation and direct inhibitors of RAS.

Figure 4.

From left to right: ① RAS is inactive when bound to GDP. ② RTK activation results in recruitment of GRB2/SOS complex to the PM where SOS promotes GDP release from RAS and formation of transient nucleotide-free state (apo-RAS; ③). ④ Binding of GTP leads to RAS recruitment of effectors. ⑤ Subsequent dimerization of the RAS/effector complex activates effectors initiating signaling cascades. RAS inactivation occurs through GTP hydrolysis catalyzed by GAPs. Numbers indicate points of direct RAS inhibition: ① G12C inhibitors (section 2.2.1.2.); ② Inhibitors of SOS-RAS (sections 2.2.1.3., 2.2.1.4., 2.2.2.1., and 2.2.2.5.); ③ Inhibitors of apo-RAS (section 2.2.2.1.) ④ Inhibitors of effector interactions (sections 2.2.1.3., 2.2.1.5., 2.2.2.1., 2.2.2.3., 2.2.2.4., 2.2.2.5., 2.2.2.6., and 2.2.2.7.); ⑤ Anti-RAS Biologics (see sections 2.2.2.6., and 2.2.2.7.). Coloring of RAS molecule is the same as in Fig. 2.