PROTACs for Lymphoma

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Targeted therapies are drugs specifically designed to attack lymphoma cells, and targeted proteins are usually presented more commonly in lymphoma cells than in healthy cells. PROTAC is promising in lymphoma treatment because it selectively and effectively promotes the degradation of tumor-associated proteins, which results in fewer adverse events and side effects on healthy cells. As an expert in PROTAC development, BOC Sciences offers comprehensive PROTAC design and development services for lymphoma drug discovery.

Introduction

Lymphoma is one of the most common types of cancer, and it may take place at any age. Luckily, it is almost always treatable. Mechanistically, lymphoma is a type of blood cancer that develops when white blood cells named lymphocytes grow out of control. The two major types of lymphoma are Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), and over 70 different types of lymphoma have been discovered. Treatment of lymphoma may involve one or more of the followings: chemotherapy, radiation therapy, proton therapy, targeted therapy, and surgery. Compared to chemotherapy, lymphoma cells targeted therapy revealed higher efficiency.

PROTAC technology is an emerging targeted protein degradation therapy that selectively degrades pathogenic protein. PROTAC is a unique bifunctional molecule that promotes protein degradation by binding the protein of interest (POI) and an E3 ligase to form a trimeric complex, hence promoting ubiquitination of the target protein and proteasomal degradation.

PROTACs Technology for Lymphoma Therapy

PROTAC utilizes the naturally occurring intracellular ubiquitin-proteasome system to selectively degrade target proteins as it contains a small-molecule ligand that localizes target proteins. As PROTAC technology matures, this innovative therapeutic approach shows its potential in lymphoma treatment. For example, anaplastic large-cell non-Hodgkin’s lymphoma (ALCL) is associated with Anaplastic lymphoma kinase (ALK), diffuse large B cell lymphoma is associated with B-cell lymphoma 6 (BCL6), and PROTACs have demonstrated the potential to degrade these disease-related targets.

Other promising PROTAC molecules for lymphoma treatment have been published in academic articles. After years of development, PROTAC technology has slowly moved from academia to industry, and PROTAC development programs were disclosed by pharmaceutical and biotechnology companies. To our knowledge, three PROTAC drug development pipelines are in the early clinical development: ANX-2127 and ANX-5948 targeting BTK for B cell malignancies and autoimmune diseases, and KT-413 targeting IRAK4 for DLBLC.

Our Services

As a leading CRO in the pharmaceutical field, BOC Sciences is dedicated to the design, discovery, and synthesis of effective PROTACs for lymphoma treatment to assist our clients in developing new PROTAC molecules. Our well-established PROTAC platform enables new insights for lymphoma treatment, including:

• PROTACs for DLBCL
• PROTACs for ALCL
• PROTACs for CML

Our Advantages

• Dedicated to the development of PROTAC for lymphoma treatment
• Well-established PROTAC platform
• Expertise and experienced scientific team
• Data analysis, detailed results reporting and discussion
• Highly reliable and reproducible results
• Quality one-stop service and competitive price

Project Workflow

References:

1. McCoull, W., et al., Development of a Novel B-Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6, ACS Chem. Biol., 2018, 13, 11, 3131-3141.
2. Zhang, C., et al., Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK), Eur J Med Chem., 2018, 151: 304-314.

* PROTAC^® is a registered trademark of Arvinas Operations, Inc., and is used under license.