Additional Relevant Details
In preclinical testing, ARQ 531 demonstrated biochemical inhibition of both wild type and C481S-mutant BTK at sub-nanomolar levels and potent cellular inhibition in C481S-mutant BTK cells that are resistant to ibrutinib. This molecule also exhibits a distinct kinase selectivity profile with inhibitory activity against several key oncogenic drivers related to ibrutinib resistance. It is currently estimated that about 10% of patients treated with ibrutinib develop resistance with over 80% presenting the C481S mutation. This incidence rate is expected to increase.Additionally, the compound potently suppresses cell proliferation of hematological malignancies in vitro, with B-cell receptor signaling inhibition. ARQ 531 also demonstrates strong in vivo target and pathway inhibition of phospho-BTK with potent and durable growth suppression.