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Primetech Corporation
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Primetech Corporation
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Harvard Bioscience
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New Era Pump Systems Inc
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MiniMed Inc
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Bioanalytical Systems Inc
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Image Search Results
Journal: Cancer Discovery
Article Title: Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRAS G12C
doi: 10.1158/2159-8290.CD-22-0158
Figure Lengend Snippet: JDQ443 displays antitumor activity across a range of cell-derived, KRAS G12C -dependent mouse tumor models, with efficacy driven by daily AUC. A, Aggregated best tumor growth inhibition in six KRAS G12C tumor models. JDQ443 efficacy was evaluated after oral dosing of 10, 30, and 100 mg/kg/day in six human KRAS G12C -mutant CDX models in mice. NSCLC cell line models are depicted in red, whereas PDAC (MIA Paca-2) and esophageal (KYSE410) cancer cell line models are shown in blue. Data are means from 2–11 independent in vivo studies. %Regr. is percentage tumor volume regression [–(Δtreated/treated at baseline) × 100], and %T/C is percentage tumor volume growth ratio [(Δtreated/Δcontrol) × 100]. B–G, CDX-bearing mice with KRAS G12C -mutated ( C–G ) and non–G12C-mutated (NCI-441, KRAS G12V ; B ) tumors were treated orally (p.o.) with JDQ443 at the indicated doses and schedules. G, LU99 tumor–bearing mice were treated with JDQ443 by continuous intravenous infusion using a programmable microinfusion pump. H and I, Simulated population-PK/PD metrics of daily AUC of JDQ443 in mouse blood ( H ) and average free KRAS G12C levels in tumor at steady state ( I ) are correlated with the observed efficacy in LU99 (%T/C or % regression). Points correspond to the mean and the error bars to ± 1 SD of the simulated PK/PD metrics based on 100 simulations and observed efficacy metrics. *, P < 0.05 versus vehicle; #, P < 0.05 versus each other, by one-way ANOVA.
Article Snippet: To assess the effect of continuous dosing on tumor growth, LU99 tumor–bearing nude mice were implanted subcutaneously with a
Techniques: Activity Assay, Derivative Assay, Inhibition, Mutagenesis, In Vivo