Figure 3 from Glecirasib, a Potent and Selective Covalent KRAS G12C Inhibitor Exhibiting Synergism with Cetuximab or SHP2 Inhibitor JAB-3312

<p>Glecirasib inhibited ERK phosphorylation and growth of tumors carrying the KRAS G12C mutation <i>in vivo</i>. <b>A–C,</b> PK/PD studies of a single-dose glecirasib administration in NCI-H358 lung cancer xenograft tumors bearing in the flank of mice. Dose response following a single dose of glecirasib is shown in <b>A</b>. Time-dependent PK/PD properties after a single dose of 30 mg/kg and 100 mg/kg glecirasib are shown in <b>B</b> and <b>C</b>, respectively. After 8 hours, glecirasib concentrations in both plasma and tumor in the 30 mg/kg group, as well as the plasma drug concentration in the 100 mg/kg group, were below the quantification limit (plasma: 1 ng/mL; tumor: 5.5 ng/g). Glecirasib concentrations in plasma and tumor tissue were quantified by LC/MS-MS, whereas p-ERK levels in tumors were measured by HTRF. Three mice per group. <b>D–F,</b><i>In vivo</i> efficacy studies of glecirasib in CDX models: NCI-H1373 lung cancer (<b>D</b>), NCI-H358 lung cancer (<b>E</b>), and MIA PaCa-2 pancreatic cancer (<b>F</b>). NCI-H1373 and MIA PaCa-2 CDX models: six mice per group; NCI-H358 CDX model: eight mice per group. Glecirasib was administrated once a day orally. <b>G</b> and <b>H,</b> Tumor growth curves (<b>G</b>) and mice body weight curves (<b>H</b>) of the LUN156 lung cancer PDX model after treatment with glecirasib. Six mice per group. All data are represented as the mean ± SEM. conc., concentration; <i>p</i>.<i>o</i>., orally; QD, once a day.</p>