Name: ARD-2128
Brand: BOC Sciences
Price: 699 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

25 mg

$699

In stock

250 mg

$1990

In stock

Purity

≥98%

Solubility

Soluble in DMSO

Appearance

Light Yellow to Green Yellow Solid

Storage

Store at -20°C

IUPACName

N-[3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]-4-[4-[[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidin-4-yl]methyl]piperazin-1-yl]benzamide

Synonyms

ARD2128; ARD 2128; N-[(1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]-4-[4-[[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidin-4-yl]methyl]piperazin-1-yl]benzamide

Boiling Point

1000.4±65.0°C at 760 Torr

Density

1.39±0.1 g/cm3

InChI Key

BWDWHHAZFQBJQL-JABICJEXNA-N

InChI

InChI=1S/C45H50ClN7O6/c1-44(2)42(45(3,4)43(44)59-32-11-7-29(25-47)35(46)24-32)49-38(55)28-5-8-30(9-6-28)52-21-19-50(20-22-52)26-27-15-17-51(18-16-27)31-10-12-33-34(23-31)41(58)53(40(33)57)36-13-14-37(54)48-39(36)56/h5-12,23-24,27,36,42-43H,13-22,26H2,1-4H3,(H,49,55)(H,48,54,56)/t36?,42-,43-

SMILES

N#CC1=CC=C(OC2C(C)(C)C(NC(=O)C3=CC=C(C=C3)N4CCN(CC4)CC5CCN(C6=CC=C7C(=O)N(C(=O)C7=C6)C8C(=O)NC(=O)CC8)CC5)C2(C)C)C=C1Cl

Mechanism

Target: Targets androgen receptor (AR) for experimental targeted protein degradation studies.

Binding Site: Binds the AR ligand-binding domain and cereblon thalidomide-binding pocket to support productive ternary complex formation.

Mechanism of Action: ARD-2128 is designed for use in PROTAC or targeted protein degradation experiments directed toward androgen receptor (AR). The bifunctional molecule links a target-recognition element to cereblon, promoting proximity between the protein of interest and ubiquitination machinery. Productive ternary-complex formation can drive polyubiquitination and proteasome-dependent target depletion, allowing researchers to compare pharmacological inhibition with protein removal. It is suitable for evaluating degradation potency, kinetics, pathway selectivity, and downstream signaling consequences in engineered or disease-relevant cellular models.

Applications

• PROTAC-Enhanced Drug Discovery: ARD-2128 serves as a powerful tool in drug discovery by facilitating the selective degradation of pathogenic proteins. Its use in research enables the identification of novel therapeutic targets through the modulation of protein levels, advancing the development of next-generation treatments.

• Targeted Protein Degradation Studies: ARD-2128 is instrumental in investigating the mechanisms of targeted protein degradation. By selectively degrading specific proteins, researchers can study the effects on cellular pathways and elucidate the roles of these proteins in disease progression.

• Functional Genomics Research: Utilizing ARD-2128 in functional genomics allows for the precise knockdown of proteins, aiding in the understanding of gene function. This approach is pivotal for dissecting complex biological systems and identifying potential genetic vulnerabilities.

• Mechanistic Insights into PROTACs: ARD-2128 provides a model for studying the mechanistic action of PROTACs, offering insights into their binding and degradation processes. Researchers can leverage this information to design more efficient and selective protein degraders.

1. Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

Lijie Zhao, Weiguo Xiang, Xin Han, Bo Wen, Shaomeng Wang, Donna McEachern, Yu Wang, Aleksas Matvekas, Duxin Sun, Bukeyan Miao, Hoda Metwally, Chong Qin, Lu Wang J Med Chem . 2021 Sep 9;64(17):12831-12854. doi: 10.1021/acs.jmedchem.1c00882.

Proteolysis targeting chimera (PROTAC) small-molecule degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 being the best compound. ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders.

HNMR

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂