Name: ARD-2585
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Solubility

Soluble in DMSO

Storage

Store at -20°C

IUPACName

N-[(1r,4r)-4-(3-chloro-4-cyano-N-methylanilino)cyclohexyl]-4-[4-[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]azetidin-3-yl]piperazin-1-yl]benzamide

Synonyms

Benzamide, N-[trans-4-[(3-chloro-4-cyanophenyl)methylamino]cyclohexyl]-4-[4-[1-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]-3-azetidinyl]-1-piperazinyl]-; N-((1r,4r)-4-((3-chloro-4-cyanophenyl)(methyl)amino)cyclohexyl)-4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)piperazin-1-yl)benzamide; N-[trans-4-[(3-Chloro-4-cyanophenyl)methylamino]cyclohexyl]-4-[4-[1-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]-3-azetidinyl]-1-piperazinyl]benzamide; ARD 2585; ARD2585

Boiling Point

1032.7±65.0°C at 760 Torr

Density

1.46±0.1 g/cm3

InChI Key

LUCHABJUYSYJAT-RVWRWSNSNA-N

InChI

InChI=1S/C41H43ClN8O5/c1-46(30-9-4-26(22-43)35(42)21-30)28-10-5-27(6-11-28)44-38(52)25-2-7-29(8-3-25)47-16-18-48(19-17-47)32-23-49(24-32)31-12-13-33-34(20-31)41(55)50(40(33)54)36-14-15-37(51)45-39(36)53/h2-4,7-9,12-13,20-21,27-28,32,36H,5-6,10-11,14-19,23-24H2,1H3,(H,44,52)(H,45,51,53)/t27-,28-,36?

SMILES

N#CC1=CC=C(C=C1Cl)N(C)C2CCC(NC(=O)C3=CC=C(C=C3)N4CCN(CC4)C5CN(C6=CC=C7C(=O)N(C(=O)C7=C6)C8C(=O)NC(=O)CC8)C5)CC2

Mechanism

Target: ARD-2585 selectively targets androgen receptor, including amplified and mutant AR forms.

Binding site: Its AR ligand binds the androgen receptor ligand-binding domain.

Mechanism of action: ARD-2585 is a highly potent PROTAC androgen receptor degrader designed to remove AR protein through the ubiquitin-proteasome system. It combines an AR-binding ligand with an E3 ligase-recruiting element, promoting ternary-complex formation, AR ubiquitination, and proteasomal degradation. Reported cellular studies show subnanomolar degradation potency in AR-amplified and AR-mutant models, supporting its use as a research tool for robust AR pathway suppression. ARD-2585 enables investigation of receptor degradation kinetics, AR transcriptional dependency, resistance-associated receptor biology, and differences between antagonism and complete AR protein depletion.

Applications

• PROTAC-Assisted Oncology Research: ARD-2585 is utilized in oncology research to selectively degrade oncogenic proteins. By harnessing the body's proteolytic machinery, it facilitates the removal of proteins that drive tumorigenesis, offering a powerful tool for elucidating cancer pathogenesis and identifying novel therapeutic targets.

• Targeted Degradation in Neurodegenerative Studies: ARD-2585 enables researchers to investigate the role of specific proteins in neurodegenerative diseases. Through precise protein degradation, it aids in dissecting proteinopathies and understanding their contribution to disease progression, ultimately advancing therapeutic strategies.

• Drug Resistance Mechanism Exploration via PROTACs: Utilizing ARD-2585, scientists can explore mechanisms of drug resistance by targeting proteins that confer resistance to conventional therapies. This approach provides insights into overcoming resistance and optimizing treatment regimens.

• PROTAC-Driven Signal Transduction Analysis: ARD-2585 serves as a crucial tool in studying signal transduction pathways. By degrading key signaling proteins, researchers can dissect pathway dynamics and interactions, contributing to a deeper understanding of cellular communication and potential points of intervention.

1. Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer

Hoda Metwally,Bukeyan Miao,Weiguo Xiang,Aleksas Matvekas,Miao He,Bo Wen,Lu Wang,Yu Wang,Paul D Kirchhoff,Duxin Sun,Shaomeng Wang,Xin Han,Lijie Zhao,Chong Qin,Donna McEachern J Med Chem . 2021 Sep 23;64(18):13487-13509. doi: 10.1021/acs.jmedchem.1c00900.

We report herein the discovery of exceptionally potent and orally bioavailable PROTAC AR degraders with ARD-2585 being the most promising compound. ARD-2585 achieves DC50values of ≤0.1 nM in the VCaP cell line with AR gene amplification and in the LNCaP cell line carrying an AR mutation. It potently inhibits cell growth with IC50values of 1.5 and 16.2 nM in the VCaP and LNCaP cell lines, respectively, and achieves excellent pharmacokinetics and 51% of oral bioavailability in mice. It is more efficacious than enzalutamide in inhibition of VCaP tumor growth and does not cause any sign of toxicity in mice. ARD-2585 is a promising AR degrader for extensive investigations for the treatment of advanced prostate cancer.

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It is commonly abbreviated as: C₁V₁ = C₂V₂