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    over2years
    Systematic analysis and molecular profiling of EGFR allosteric inhibitor cross-reactivity across the proto-oncogenic ErbB family kinases by integrating dynamics simulation, energetics calculation and biochemical assay. (PubMed, Eur Biophys J)
    It is found that allosteric and orthosteric inhibitors exhibit moderate and modest cross-reactivity across the ErbB family, respectively, but the former generally has a higher binding potency than the latter due to the additional energy cost used for inducing kinase conformational change. Moreover, most allosteric inhibitors can be sensitized by Her2 T798M gatekeeper mutation, a counterpart of EGFR T790M gatekeeper mutation that has been previously reported to cause generic drug resistance for orthosteric inhibitors.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    EGFR mutation • HER-2 mutation • EGFR T790M • EGFR C797S • HER-2 T798M
    almost5years
    A Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies (clinicaltrials.gov)
    P2, N=150, Recruiting, Spectrum Pharmaceuticals, Inc | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • HER-2 amplification • EGFR L858R • HER-2 mutation • EGFR T790M • HER-2 exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • HER-2 S310F • HER-2 V777L • EGFR E709K • HER-2 I655V • HER-2 L869R • HER-2 V842I • EGFR P596L • EGFR R222C • HER-2 T798M • EGFR E746 • HER-2 D769H • HER-2 R678Q • HER-2 T798I • HER-2 mutation + HER-2 T798I • EGFR V774M
    |
    Pozenveo (poziotinib)