Name: AU-15330
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

Store at 2-8°C, stored under nitrogen, away from moisture

IUPACName

(2S,4R)-1-[(2S)-2-[[2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide

Synonyms

AU 15330; AU15330; (2S,4R)-1-((S)-2-(2-(4-(3-Amino-6-(2-hydroxyphenyl)pyridazin-4-yl)piperazin-1-yl)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

Boiling Point

1046.2±65.0°C at 760 Torr

Density

1.310±0.06 g/cm3

InChI Key

HDCCMCFIGHIDJR-TUDDPRDOSA-N

InChI

InChI=1S/C39H49N9O5S/c1-23(25-10-12-26(13-11-25)34-24(2)41-22-54-34)42-37(52)31-18-27(49)20-48(31)38(53)35(39(3,4)5)43-33(51)21-46-14-16-47(17-15-46)30-19-29(44-45-36(30)40)28-8-6-7-9-32(28)50/h6-13,19,22-23,27,31,35,49-50H,14-18,20-21H2,1-5H3,(H2,40,45)(H,42,52)(H,43,51)/t23-,27+,31-,35+/m0/s1

SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)C(C)NC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CN4CCN(CC4)C5=CC(=NN=C5N)C6=CC=CC=C6O)O

Mechanism

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

Binding Site: Binds the AR ligand-binding domain and von Hippel-Lindau substrate-recognition pocket to support productive ternary complex formation.

Mechanism of Action: AU-15330 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 VHL, 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-Mediated Kinase Degradation: AU-15330 serves as a potent tool for selectively degrading kinases implicated in oncogenic signaling pathways. By harnessing the ubiquitin-proteasome system, researchers can utilize this PROTAC to dissect kinase functions and interactions, advancing the understanding of cancer biology and aiding in the identification of novel therapeutic targets.

• Targeted Degradation in Neurodegeneration: This PROTAC is instrumental in studying the role of misfolded proteins in neurodegenerative diseases. AU-15330 enables the selective degradation of pathogenic proteins, providing insights into disease mechanisms and facilitating the exploration of potential therapeutic strategies for conditions such as Alzheimer's and Parkinson's diseases.

• PROTAC-Driven Epigenetic Modulation: AU-15330 is employed in research focusing on the degradation of epigenetic regulators. By specifically targeting proteins involved in chromatin remodeling and gene expression, this PROTAC aids in elucidating epigenetic modifications' impact on various biological processes and diseases, paving the way for innovative epigenetic therapies.

• Selective Degradation in Immune Response: Researchers utilize AU-15330 to investigate the degradation of proteins that modulate immune signaling pathways. This approach allows the study of immune system dynamics and the identification of key regulatory nodes that could be targeted for therapeutic intervention in autoimmune disorders and inflammatory diseases.

1. Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer

Josh N Vo, Steven Kregel, Mital S Bhakta, Murali Ramachandra, Sanjana Eyunni, Andrew D Delekta, Sanjita Sasmal, Abhijit Parolia, Ulka Vaishampayan, Ingrid J Apel, Rahul Mannan, Pushpinder Bawa, Subhendu Mukherjee, Chandrasekhar Abbineni, Xiaoju Wang, Nora M Navone, Fengyun Su, Alexey I Nesvizhskii, Yuanyuan Qiao, Yu Chang, Rui Wang, Yuzhuo Wang, Rohit Mehra, Lanbo Xiao, Stephanie A Simko, Yuping Zhang, Kiran Aithal, Heng Zheng, Marco Blanchette, Lisa McMurry, Sandra E Carson, Mustapha Jaber, Xuhong Cao, Jay Ghurye, Sylvia Zelenka-Wang, Leena Khare, Susanta Samajdar, Arul M Chinnaiyan Nature . 2022 Jan;601(7893):434-439. doi: 10.1038/s41586-021-04246-z.

The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling1and is altered in over 20% of cancers2,3. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)+forkhead box A1 (FOXA1)+prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.

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It is commonly abbreviated as: C₁V₁ = C₂V₂