ARD-69

ARD-69 is a PROTAC degrader based on the E3 ubiquitin ligase VHL and targeting the androgen receptor, which can induce androgen receptor (AR) protein degradation in AR-positive prostate cancer cells. ARD-69 inhibits AR-regulated gene expression, binds to the AR ligand binding domain at one end and binds to VHL at the other end, prompting AR to be recruited to the E3 ubiquitin ligase complex, triggering proteasome degradation, thereby inhibiting AR signaling pathways and downstream gene expression (such as PSA, TMPRSS2) . ARD-69 can be used to study the treatment of castration-resistant prostate cancer (mCRPC) [1][2][3]. ARD-69 is composed of a target protein ligand (pink part) AR antagonist 14 (HY-172624), a PROTAC linker (black part) tert-Butyl 4-ethynyl-[1,4'-bipiperidine]-1'-carboxylate (HY-W442074), and a VHL-type E3 ubiquitinase ligand (blue part) VH 101, acid (HY-47070) ; among them, the VHL ligand and the linker can form a conjugate VH 101-amide-piperidine-Pip-alkyne (HY-172625) .

Product Specifications

CAS Number

[2316837-10-0]

Product Name Alternative

Y-39991

UNSPSC

12352005

Target

Androgen Receptor; PROTACs

Type

Reference compound

Related Pathways

PROTAC; Vitamin D Related/Nuclear Receptor

Applications

Cancer-programmed cell death

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/ARD-69.html

Purity

99.61

Solubility

DMSO : ≥ 200 mg/mL

Smiles

ClC1=CC(O[C@H]2C(C)(C)[C@H](NC(C3=CC=C(C#CC4CCN(C5CCN(C(C[C@H](NC([C@H]6N(C([C@@H](NC(C7(CC7)F)=O)C(C)(C)C)=O)C[C@H](O)C6)=O)C8=CC=C(C9=C(C)N=CS9)C=C8)=O)CC5)CC4)C=C3)=O)C2(C)C)=CC=C1C#N

Molecular Formula

C62H74ClFN8O7S

Molecular Weight

1129.82

References & Citations

[1]Han X, et al. Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer. J Med Chem. 2019 Jan 10.|[2]Du W. Advances in AR-targeting chimeras: a case study of proteolysis-targeting chimeras from bench to bedside. Future Med Chem. 2022 Oct;14 (20) :1471-1489.|[3]Xiang, et al. Recent advances in targeting the androgen receptor with PROTACS. 2022 Medicinal Chemistry Reviews (2022) .