^
    almost4years
    [VIRTUAL] AGX87 - An IND-stage potent and selective next-generation NTRK/ROS1 inhibitor of WT and clinical resistant mutants with superiority over tyrosine kinase inhibitors currently approved or in development (AACR 2021)
    While the 1st generation TKIs larotrectinib (LOXO101, LAR), entrectinib (ENT) and crizotinib (CRI) have provided effective initial treatment for patients with cancers harboring these mutations, acquired resistance including secondary kinase domain mutations invariably arise. Kinase and cell proliferation inhibition and in vivo antitumor activity were determined using recombinant kinases and engineered NIH3T3 or Ba/F3 cells expressing WT or mutated TRKs and ROS1, respectively...Against the resistant solvent-front (G595R) mutant AGX87 was >1000-fold more potent (IC50=0.2 nM) than LAR and ENT and 20-fold more potent than LOXO195... AGX87 demonstrated best-in-class activity against WT and mutated TRKs and ROS1 and exhibited excellent drug-like properties. IND enabling studies are in progress.
    Clinical • Head-to-Head
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK2 fusion • ROS1 G2032R • NTRK1 G595R • NTRK1 G667C
    |
    Xalkori (crizotinib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • selitrectinib (BAY 2731954) • AGX87