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ARV-110 is an orally active, specific androgen receptor (AR) PROTAC degrader. ARV-110 promotes ubiquitination and degradation of AR. ARV-110 can be used for the research of prostate cancer[1].

ARV-110 completely degrades AR in all cell lines tested, with an observed 50% degradation concentration (DC50) ARV-110 (10 nM; 0.5-24 hours) leads to AR degradation in VCaP cells in a time-dependent manner[2].ARV-110 (10-1000 nM) suppresses the expression of the AR-target gene PSA, inhibits AR-dependent cell proliferation, and induces apoptosis at low nanomolar concentrations[2].ARV-110 (0.01 nM-100 nM) degrades clinically relevant mutant AR proteins (WT AR, F876L, T877A, M896V and H874V), and retains activity in a high androgen environment (R1881, 100 nM) in VCaP cells[2].

ARV-110 (oral gavage; 1 mg/kg; QD) exhibits a greater than 90% AR degradation in vivo. In LNCaP, VCaP and prostate cancer patient derived xenograft (PDX) models, ARV-110 also exhibits significant inhibition of tumor growth and AR signaling[2].ARV-110 (oral gavage; 3 or 10 mpk; 30 days) demonstrates in vivo efficacy and reduction of AR-target gene expression in a long term, castrate, enzalutamide-resistant VCaP tumor model. The TGI are 70% and 60% for 3 mpk and 10 mpk dosage. Respectively[2].

[1]. Taavi Neklesa, et al. ARV-110: An androgen receptor PROTAC degrader for prostate cancer. American Association for Cancer Research. 2018. 78 (13): pp. 5236.

[2]. Taavi K Neklesa,et al. ARV-110: an oral androgen receptor PROTAC degrader for prostate cancer. GU ASCO 2019

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