Delving into the Latest Updates on ARD-2051 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Proteolysis-targeting chimeras (PROTAC)

Synonyms

Target

AR

Mechanism

AR modulators(Androgen Receptor modulators)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Advanced Prostate Carcinoma

Inactive Indication-

Originator Organization

University of Michigan

Active Organization

University of Michigan

Inactive Organization-

Drug Highest PhaseDiscovery

First Approval Date-

Regulation-

Structure

Molecular FormulaC43H45ClN8O5

InChIKeyWBMJNGGUHCHFHY-YNJTUNHHSA-N

CAS Registry2632305-18-9

Author: Takyi-Williams, John ; Han, Xin ; McEachern, Donna ; Zhao, Lijie ; Qin, Chong ; Yang, Chao-Yie ; Wang, Lu ; Sun, Duxin ; Miao, Bukeyan ; Ator, Mark ; Xu, Tianfeng ; Wang, Yu ; Xiang, Weiguo ; Wang, Mi ; Matvekas, Aleksas ; Wen, Bo ; Mckean, Robert ; Metwally, Hoda ; Kirchhoff, Paul D ; Wang, Shaomeng ; Lu, Jianfeng

We report the discovery of ARD-2051 as a potent and orally efficacious androgen receptor (AR) proteolysis-targeting chimera degrader. ARD-2051 achieves DC₅₀ values of 0.6 nM and D_max >90% in inducing AR protein degradation in both the LNCaP and VCaP prostate cancer cell lines, potently and effectively suppresses AR-regulated genes, and inhibits cancer cell growth. ARD-2051 achieves a good oral bioavailability and pharmacokinetic profile in mouse, rat, and dog. A single oral dose of ARD-2051 strongly reduces AR protein and suppresses AR-regulated gene expression in the VCaP xenograft tumor tissue in mice. Oral administration of ARD-2051 effectively inhibits VCaP tumor growth and causes no signs of toxicity in mice. ARD-2051 is a promising AR degrader for advanced preclinical development for the treatment of AR+ human cancers.

100 Deals associated with ARD-2051

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