ID11916 is an orally available androgen receptor (AR) antagonist and PDE5 inhibitor, modulates AR-dependent and AR-independent pathways by activating cGMP-dependent protein kinase (PKG).
ID11916 effectively blocks androgen binding to AR, nuclear translocation, and androgen-dependent transcriptional activity of AR, while increasing intracellular cGMP levels and activating PKG via phosphodiesterase 5 (PDE5) inhibition.
ID11916 demonstrated potent anti-cancer effect in prostate cancer cell lines VCaP and 22Rv1, but not enzalutamide ID11916 showed approximately 60-fold greater anti-proliferative activity (IC50=2.77 uM) in VCaP, than enzalutamide.
ID11916 demonstrates greater potency in colony formation assays than enzalutamide in AR-positive breast cancer cell lines SK-BR-3 (ID11916 IC50: 0.653 μM vs Enzalutamide IC50: > 30.0 μM) and MDA-MB-231 (ID11916 IC50: 1.96 μM vs Enzalutamide IC50: 18.1 μM).
ID11916 shows superior tumor growth inhibition in MDA-MB-453 xenograft model.