UT-105 is a small-molecule, irreversible, selective androgen receptor (AR) degrader (SARD) and irreversible inhibitor, binds to AR N-terminal domain (NTD) and inhibits both the AR and AR splice variants (AR-SVs).
UT-105 selectively inhibits wild-type and enzalutamide-resistant mutant AR transactivation with IC50 of 59.4 nM and 36.5 nM, respectively.
UT-105 is selective to AR and does not inhibit the transactivation of glucocorticoid (GR) or mineralocorticoid (MR) receptors in a panel of kinases (468) and 168 GPCRs.
UT-105 binds to AR NTD, but not ligand-binding domain (LBD).
UT-105 effectively degrades AR, irreversibly inhibits AR, inhibits AR-target genes, and significantly inhibits proliferation and colony formation in cells expressing AR and AR-V7.
UT-105 (60 mg/kg/day), but not enzalutamide and bicalutamide, inhibits TNBC tumor growth in orthotopic MDA-MB-453 TNBC model with a tumor growth inhibition (TGI) of >90%.
UT-105 inhibits STAT1 phosphorylation, effectively reduces IRF1, IRF7, and IRF9 expression in tumors, also inhibits the phosphorylation of STAT1, STAT3, and AKT in MDA-MB-453 tumors.