Name: HDAC6 degrader 9c
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 for short term (days to weeks) or -20°C for long term (months to years)

IUPACName

N-[(E)-[4-[2-[2-[2-[4-[[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]phenyl]methylideneamino]-N'-hydroxyoctanediamide

Synonyms

dHDAC6 9c; (E)-8-(2-(4-(2-(2-(2-(4-(((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)benzylidene)hydrazineyl)-N-hydroxy-8-oxooctanamide; 8-[(2E)-2-{4-[2-(2-{2-[4-({[2-(2,6-Dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]amino}methyl)-1H-1,2,3-triazol-1-yl]ethoxy}ethoxy)ethoxy]benzylidene}hydrazino]-N-hydroxy-8-oxooctanamide; Octanoic acid, 8-(hydroxyamino)-8-oxo-, 2-[(1E)-[4-[2-[2-[2-[4-[[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]methyl]-1H-1,2,3-triazol-1-yl]ethoxy]ethoxy]ethoxy]phenyl]methylene]hydrazide; 8-(Hydroxyamino)-8-oxooctanoic acid (2E)-2-[[4-[2-[2-[2-[4-[[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]methyl]-1H-1,2,3-triazol-1-yl]ethoxy]ethoxy]ethoxy]phenyl]methylene]hydrazide

Density

1.44±0.1 g/cm3

InChI Key

MHILTYZXXFOWJH-WVKHYPTHSA-N

InChI

InChI=1S/C37H45N9O10/c47-31-15-14-30(35(50)40-31)46-36(51)28-6-5-7-29(34(28)37(46)52)38-23-26-24-45(44-41-26)16-17-54-18-19-55-20-21-56-27-12-10-25(11-13-27)22-39-42-32(48)8-3-1-2-4-9-33(49)43-53/h5-7,10-13,22,24,30,38,53H,1-4,8-9,14-21,23H2,(H,42,48)(H,43,49)(H,40,47,50)/b39-22+

SMILES

C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NCC4=CN(N=N4)CCOCCOCCOC5=CC=C(C=C5)C=NNC(=O)CCCCCCC(=O)NO

Mechanism

Target: Targets estrogen receptor alpha (ERα) for experimental targeted protein degradation studies.

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

Mechanism of Action: HDAC6 degrader 9c is designed for use in PROTAC or targeted protein degradation experiments directed toward estrogen receptor alpha (ERα). 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-Mediated HDAC6 Degradation: HDAC6 degrader 9c facilitates the selective degradation of HDAC6, a key enzyme involved in protein acetylation and cellular stress responses. This application is pivotal for researchers aiming to dissect HDAC6's role in neurodegenerative diseases and cancer, offering insights into its biological functions through targeted protein degradation.

• Targeted Protein Degradation in Cancer Research: Utilizing HDAC6 degrader 9c allows researchers to explore the therapeutic potential of HDAC6 inhibition in oncology. By promoting the degradation of HDAC6, this PROTAC aids in the study of tumorigenic pathways and the development of novel cancer treatment strategies.

• Neurodegenerative Disease Mechanism Studies: HDAC6 degrader 9c serves as a valuable tool for investigating the pathological mechanisms underlying neurodegenerative disorders. Through targeted degradation, it enables the examination of HDAC6's involvement in protein aggregation and neuronal toxicity, providing a pathway to potential therapeutic interventions.

• Cellular Stress Response Analysis: By employing HDAC6 degrader 9c, scientists can delve into the cellular stress response mechanisms modulated by HDAC6. This application is crucial for understanding how cells manage proteostasis and adapt to stress, thereby contributing to the broader field of cell biology research.

1. Development of the first small molecule histone deacetylase 6 (HDAC6) degraders.

Yang, K., Song, Y., Xie, H., Wu, H., Wu, Y.T., Leisten, E.D. and Tang, W., 2018. Bioorganic & medicinal chemistry letters, 28(14), pp.2493-2497.

Histone deacetylases (HDACs) decrease the acetylation level of histones and other non-histone proteins. Over expression of HDACs have been observed in cancers and other diseases. Targeted protein degradation by "hijacking" the natural ubiquitin-proteasome-system (UPS) recently emerged as a novel technology to "knock-out" endogenous disease-causing proteins. We applied this strategy to the development of the first small molecule degraders for zinc-dependent HDACs by conjugating non-selective HDAC inhibitors with E3 ubiquitin ligase ligands. Through cell-based assays, we discovered novel bifunctional molecules (dHDAC6) that could selectively degrade HDAC6. Further mechanistic studies indicated that HDAC6 was selectively removed by the UPS.

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