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    BIOMARKER:

    RET G810R

    i
    Entrez ID:
    5979
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    5ms
    Discovery and Synthesis of Heterobifunctional Degraders of Rearranged during Transfection (RET) Kinase. (PubMed, J Med Chem)
    Importantly, in PK/PD studies, 39 exhibited a differentiated and favorable in vivo profile compared to the corresponding tyrosine kinase inhibitor (TKI), compound 3. Robust and sustained degradation of total-RET (tRET) protein and inhibition of phospho-RET (pRET) signaling were observed in TPC-1 xenograft tumors driven by RET and the RET/G810R mutant following a single dose of LDD 39 at 15 and 75 mg/kg, respectively.
    Journal
    |
    RET (Ret Proto-Oncogene) • CRBN (Cereblon)
    |
    RET mutation • RET G810R • RET V804M • RET V804* • RET wild-type
    6ms
    Discovery of 7-(1-methyl-1H-pyrazol-4-yl)-1,6-naphthyridine derivatives as potent inhibitors of rearranged during transfection (RET) and RET solvent-front mutants for overcoming selpercatinib resistance. (PubMed, Eur J Med Chem)
    Importantly, 20p exhibited highly impressive antitumor potency in both a Ba/F3-KIF5B-RETWT-derived xenograft mouse model and a selpercatinib-resistant Ba/F3-KIF5B-RETG810R-positive mutant xenograft mouse model. Overall, 20p represents a novel and promising drug lead for overcoming RET solvent-front mutation-based resistance to selpercatinib.
    Journal
    |
    RET (Ret Proto-Oncogene) • KIF5B (Kinesin Family Member 5B)
    |
    RET G810C • RET G810R • RET G810S
    |
    Retevmo (selpercatinib)