dd-03-171

DD-03-171 is an optimized small-molecule proteolysis-targeting chimera (PROTAC) that induces the degradation of Bruton tyrosine kinase (BTK), as well as IKFZ1 and IKFZ3 in certain cellular contexts, through a mechanism involving recruitment of the E3 ubiquitin ligase CRBN (cereblon) to target proteins for proteasomal destruction[1]. It is derived from the BTK inhibitor CGI-1746 conjugated to a thalidomide-like ligand via a hydrocarbon linker, enabling simultaneous degradation of BTK and the transcription factors IKFZ1/3 in selected B-cell malignancies[1][9]. In preclinical studies, DD-03-171 demonstrated enhanced antiproliferative effects compared to traditional BTK inhibitors, including activity against ibrutinib-resistant C481S-BTK mutant cancer cells[1]. It reduces tumor burden and extends survival in lymphoma patient-derived xenograft models, suggesting potential as a therapeutic strategy for mantle cell lymphoma (MCL) and other B-cell malignancies, particularly in cases with resistance to standard BTK inhibitors[1][8]. The compound acts in a proteasome- and CRBN-dependent manner, with high selectivity for BTK at the tested concentrations[1][5].

Other names

DD 03-171DD03-171DD-03-171