ARV-110 是一种具有口服活性的，特异性的雄激素受体 (AR) PROTAC 类降解剂。ARV-110 能促进 AR 的泛素化和降解，可用于前列腺癌的研究。
货号:ajcx33088
CAS:2222112-77-6
分子式:C41H43ClFN9O6
分子量：812.29
溶解度:DMSO : 26.67 mg/mL (32.83 mM; ultrasonic and warming and adjust pH to 3 with HCl and heat to 80°C)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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