ARV-110

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

ARV-110 是一种口服雄激素受体 PROTAC 降解剂，用于治疗前列腺癌。

ARV-110 is an oral degrader of androgen receptor PROTAC for prostate cancer treatment.

Bavdegalutamide completely degrades AR in all cell lines tested, with an observed 50% degradation concentration (DC50) < 1 nM.Bavdegalutamide (0.01 nM-300 nM) leads to AR degradation in LNCaP cells in a dose-dependent manner.Bavdegalutamide (10 nM; 0.5-24 hours) leads to AR degradation in VCaP cells in a time-dependent manner.Bavdegalutamide (10-1000 nM) suppresses the expression of the AR-target gene PSA, inhibits AR-dependent cell proliferation, and induces apoptosis at low nanomolar concentrations.Bavdegalutamide (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.

Bavdegalutamide (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, Bavdegalutamide also exhibits significant inhibition of tumor growth and AR signaling.Bavdegalutamide (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.

——

Endocrinology/Hormones

Androgen Receptor (AR)

Androgen Receptor

——

——

2222112-77-6

812.29

C41H43ClFN9O6

>98% (HPLC)

DMSO:46 mg/mL (56.63 mM; Need ultrasonic)

ClC1=CC(O[C@H]2CC[C@@H](CC2)NC(C3=CC=C(N=N3)N4CCC(CC4)CN5CCN(CC5)C6=CC(C(N7C8CCC(NC8=O)=O)=O)=C(C=C6F)C7=O)=O)=CC=C1C#N

——

(-20℃)

With Ice Pack

≥ 2 years