ANXA3 degrader 18a5 is a highly selective ANXA3 degrader with SPR KD of 0.08 uM, exhibits antiproliferative activity against with IC50 of 0.71 and 1.05 uM, DC50 of 3.12 uM and 1.32 uM in MDA-MB-468 and MDA-MB-231 cells, respectively.
ANXA3 degrader 18a5 shows significant improvement in ANXA3 binding activity, better cancer cell inhibition, and preferable ANXA3 selective degradation in vitro and in vivo, than (R)-SL18.
ANXA3 degrader 18a5 promotes ANXA3 degradation via the ubiquitin-proteasome pathway rather than autophagy.
ANXA3 degrader 18a5 (6 uM) degraded the ANXA3 protein by 70% in MDA-MB-231 cells, with little to no effect on ANXA4, ANXA10, and ANXA13 proteins.
ANXA3 degrader 18a5 induces apoptosis, inhibits migration, invasion, and colony formation in TNBC cells.
ANXA3 degrader 18a5 showed potent antitumor activity with low toxicity in a subcutaneous tumor xenograft model.