ARCC 4

ARCC-4 is a low-nanomolar androgen receptor (AR) degrader based on PROTAC, with a DC50 of 5 nM. ARCC-4 is an enzalutamide-based von Hippel-Lindau (VHL)-recruiting AR PROTAC and outperforms enzalutamide. ARCC-4 effectively degrades clinically relevant AR mutants associated with antiandrogen therapy[1].

Research Areas >> Cancer

Signaling Pathways >> PROTAC >> PROTAC

Signaling Pathways >> Others >> Androgen Receptor

VHL

ARCC-4 induces apoptosis and inhibiting proliferation of AR-amplified prostate cancer cells[1]. ARCC-4 enhances protein-protein interactions between AR and VHL, thereby promoting the association of the trimeric complex[1]. ARCC-4 (0.1-10,000 nM; 20 hours) potently degrades AR with a D50 of 5 nM and Dmax of over 95%[1]. ARCC-4 (100 nM; 12 hours) shows near complete AR degradation (>98%) in prostate cancer cells[1]. ARCC-4 selectively degrades AR via the proteasome but not PR-A or PR-B suppression[1]. ARCC-4 shows efficacy against clinically relevant AR mutations[1]. ARCC-4 maintains activity despite elevated androgen levels[1]. Western Blot Analysis[1] Cell Line: VCaP cells Concentration: 0.1 nM, 1 nM, 10 nM, 50 nM, 100 nM, 0.5μM, 1μM, 10 μM Incubation Time: 20 hours Result: Potently degrades AR

[1]. Salami J, et al. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance. Commun Biol. 2018 Aug 2;1:100.