ARV-110

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.

Product information

CAS Number: 2222112-77-6

Molecular Weight: 812.29

Formula: C41H43ClFN9O6

Chemical Name: N-[4-(3-chloro-4-cyanophenoxy)cyclohexyl]-6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyridazine-3-carboxamide

Smiles: N#CC1=CC=C(C=C1Cl)O[C@@H]1CC[C@H](CC1)NC(=O)C1=CC=C(N=N1)N1CCC(CN2CCN(CC2)C2=CC3=C(C=C2F)C(=O)N(C2CCC(=O)NC2=O)C3=O)CC1

InChiKey: CLCTZVRHDOAUGJ-SYVGMNBRSA-N

InChi: InChI=1S/C41H43ClFN9O6/c42-31-19-28(4-1-25(31)22-44)58-27-5-2-26(3-6-27)45-38(54)33-7-9-36(48-47-33)51-13-11-24(12-14-51)23-49-15-17-50(18-16-49)35-21-30-29(20-32(35)43)40(56)52(41(30)57)34-8-10-37(53)46-39(34)55/h1,4,7,9,19-21,24,26-27,34H,2-3,5-6,8,10-18,23H2,(H,45,54)(H,46,53,55)/t26-,27-,34?

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 26.67 mg/mL (32.83 mM; ultrasonic and warming and adjust pH to 3 with HCl and heat to 80°C).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

ARV-110 completely degrades AR in all cell lines tested, with an observed 50% degradation concentration (DC50) < 1 nM. ARV-110 (0.01 nM-300 nM) leads to AR degradation in LNCaP cells in a dose-dependent manner. ARV-110 (10 nM; 0.5-24 hours) leads to AR degradation in VCaP cells in a time-dependent manner. 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. 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.

In Vivo:

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. 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.

Products are for research use only. Not for human use.