PROTACs for Huntington Disease
As a leading CRO in the pharmaceutical field, BOC Sciences is dedicated to the design, discovery, synthesis and optimization of effective PROTACs to assist our customers’ new drug development. With our comprehensive and advanced platform, we provide PROTAC molecules design services for treating Huntington disease.
Introduction
Many neurodegenerative diseases are characterized by dysregulation of protein quality control mechanisms in neuronal cells to form intracellular protein aggregates. The accumulation of various pathogenic proteins leads to the development of different neurodegenerative diseases, including Huntington disease (HD). HD is an autosomal dominant, lethal disease resulting in a diverse range of behavioural, cognitive and physical symptoms. HD is caused by the N-terminal polyglutamine expansion of huntingtin protein (Htt). Promoting the degradation of mutant Htt (mHtt) via the ubiquitin-proteasome system (UPS) prior to aggregation would be a therapeutic strategy to delay or prevent the HD.
The UPS has been shown to play an important role in mHtt degradation. The ability of PROTACs to utilize the natural UPS in cells to promote the degradation of pathogenic proteins shows promising prospects for their HD treatment. PROTAC is a heterobifunctional compound consisting of two different ligands joined by a linker, one of the ligands recruits mHtt, the other ligand is specific for a E3 ubiquitin ligase.
PROTAC in Huntington Disease
The discovery of novel PROTAC protein degraders is one of the most promising approaches for neurologic diseases. PROTACs have important advantages with respect to other therapies, including:
- Targeting many of the proteins within the central nervous system are considered to be ‘undruggable’
- Having ‘catalytic’ activity that a single PROTAC molecule can induce the degradation of numbers of disease-causing proteins
- Holding the ability to cross the blood–brain barrier
- Having potential for oral dosing
PROTACs bring mHtt and the E3 ubiquitin ligase to a relative position that allows mHtt to be ubiquitinated and subsequently degraded by the proteasome. clAP1-based PROTAC has been reported, whose composition includes a specific ligand that can bind cellular inhibitor of apoptosis protein 1 (cIAP1). These PROTAC compounds would recruit cIAP1 to mHtt and induce selective degradation .
One-Stop Services
Related Products
BOC Sciences provides custom protein expression and purification services covering a variety of ubiquitin ligases, such as cIAP1. Our extensive product portfolio also includes PROTAC, E3 ligase ligand-linker conjugate, ligand for E3 ligase, ligand for target protein and PROTAC Linker. If you are interested in our related products, please click to learn more.
Our Advantages
- Indication-directed molecular development of PROTAC
- Customized PROTAC design services for Huntington disease
- High-quality one-stop service
- Comprehensive and advanced PROTAC platform
- Experienced experts team and extensive expertise
- Data analysis, detailed report with results and discussion
- Superior after-sale service
- Short turn-around time and competitive price
Project Workflow
References:
- Fiorillo, A., Morea, V., Colotti, G., Ilari, A., Huntingtin Ubiquitination Mechanisms and Novel Possible Therapies to Decrease the Toxic Effects of Mutated Huntingtin, J. Pers. Med., 2021, 11(12), 1309.
- Harding, R. J., Yu-feng Tong, Y., Proteostasis in Huntington's disease: disease mechanisms and therapeutic opportunities, Acta Pharmacol Sin, 2018, 39(5): 754-769.
* PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license.
