Research Area
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Description
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Cancer |
Biological Activity
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Description
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WZ8040 is a novel mutant-selective irreversible EGFRT790M inhibitor. |
Targets
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EGFR T790M |
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IC50 |
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In Vitro
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WZ8040 is 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors such as CL-387785 and HKI-272. WZ8040 treatment potently inhibits the growth of HCC827 (EGFR Del E746_A750), PC9 (EGFR Del E746_A750), H3255 (EGFR L858R), H1975 (EGFR L858R/T790M), and PC9 GR (EGFR Del E746_A750/T790M) with IC50 of 1 nM, 6 nM, 66 nM, 9 nM, and 8 nM, respectively. WZ8040 weakly inhibits the growth of HCC827 GR (EGFR E746_A750/MET amp), H1819 (ERBB2 amp), Calu-3 (ERBB2 amp), H1781 (ERBB2 Ins G776V, C), and HN11 (EGFR & ERBB2 WT) with IC50 of >3.3 μM, 738 nM, 915 nM, 744 nM, and 1.82 μM, respectively. WZ8040 is not toxic up to 10 μM against A549 (KRAS mutant) or H3122 (EML4-ALK) cells. [1] |
In Vivo
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Clinical Trials
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Features
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Inhibits EGFRT790M mutation but not wild-type EGFR. |
Protocol
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Cell Assay
[1]
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Cell Lines |
HCC827, H3255, HCC827 GR, H1975, PC9, PC9 GR, Calu-3, H1819, and Ba/F3 |
Concentrations |
Dissolved in DMSO, final concentrations ~10 μM |
Incubation Time |
72 hours |
Methods |
Cells are exposed to increasing concentrations of WZ8040 for 72 hours. Growth is assessed using the MTS survival assay. |
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