DD-03-171 + NX-5948 + GMB475 + PT-65 + SJFa

DD-03-171 + NX-5948 + GMB475 + PT-65 + SJFa is a hypothetical combination therapy consisting of investigational BTK-targeted protein degraders primarily aimed at B-cell malignancies. DD-03-171 is a cereblon-engaging PROTAC degrader derived from CGI1746 conjugated to thalidomide, potently degrading BTK (DC50=5.1 nM), IKZF1, and IKZF3 in a proteasome- and CRBN-dependent manner, suppressing signaling and proliferation in mantle cell lymphoma cells including ibrutinib-resistant C481S mutants, with demonstrated efficacy in patient-derived xenograft models. NX-5948 is an orally bioavailable, CNS-penetrant catalytic BTK degrader from Nurix Therapeutics that targets wild-type and mutant BTK forms via ubiquitination and proteasomal degradation, showing preliminary clinical efficacy in relapsed/refractory CLL/SLL and fast track designation for Waldenström macroglobulinemia. Limited public data exists on GMB475, PT-65, and SJFa, which may represent additional preclinical or early-stage BTK modulators or degraders; their inclusion suggests a multi-pronged approach to overcome BTK inhibitor resistance in lymphomas through enhanced degradation and pathway inhibition.