PROTACs for Leukemia

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BOC Sciences is a provider of drug discovery services. We have been developing PROTAC technology for nearly a decade to help our customers accelerate the development of new drugs. With the comprehensive PROTAC platform, we offer one-stop PROTAC based molecular development services for leukemia treatment.

Introduction

Leukemia is a cancer of blood-forming tissues, hindering the body's ability to fight infection. Many types of leukemia exist, ranging from mild to severe, such as chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), which include fatal malignancies. The success of treatment depends on the type of leukemia and the age of the person. Leukemias and lymphomas both belong to a group of tumors that affect the bone marrow, blood, and lymphoid system.

Treatment options for leukemia include chemotherapy, radiation therapy, and targeted therapy, etc. While some types of leukemia can be managed by watchful waiting, fatal hematologic malignancies also exist. Therefore, finding promising disease solutions remains critical and challenging. PROTACs have emerged as a novel technology in cancer treatment as targeted protein degrader. PROTAC is a heterbifunctional molecule that could simultaneously bind to the E3 ligase and target protein, thereby leading to degradation of the disease-causing protein. PROTACs have been developed for targeting leukemia related therapeutic targets, showing promising preclinical results.

PROTACs in Leukemia

A number of PROTACs have been developed to target various pathogenic proteins associated with leukemia progression, such as bromodomain-containing protein 4 (BRD4), Bruton’s tyrosine kinase (BTK), BCR-ABL, ALK, Bcl-xL, FLT-3, CDK-6, HDAC6, and STAT3. Some of them have been shown to be in vitro against cancer cells with extreme lethality and enable in vivo tumor regression in animal models.

There are many examples of PROTACs that show promise in leukemia treatment. dBET1 degrades BRD4 with sub-micromolar DC50 values and significantly inhibits the proliferation of leukemia cells in vitro and in mouse models; MT-802 exhibits activities in degradation of wild-type and mutant BTK and inhibited cell proliferation in CLL cells; GMB-475 induced degradation of BCR-ABL at sub-micromolar levels in primary CML patient cells inhibited their proliferation; etc.

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. We provide PROTAC molecules design services for leukemia therapeutics, including:

• PROTACs for CML
• PROTACs for ALL
• PROTACs for AML
• PROTACs for APL (Acute promyelocytic leukemia)
• PROTACs for T-ALL (Acute T-cell leukemia)

One-Stop Services

• PROTAC^® Design Services
• Ligand Design for E3 Ligase
• Ligand Design for Target Protein
• PROTAC^® In Vitro Evaluation
• PROTAC^® In Vivo Evaluation

Related Products

Our Advantages

• PROTAC design and optimization for the treatment of leukemia
• Well-established PROTAC platform and one-stop service
• Quality services and products
• Expertise and experienced scientific team
• Data analysis, detailed results reporting and discussion
• Highly reliable and reproducible results

Project Workflow

References:

1. Li, X., Song, Y., Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy, Journal of Hematology & Oncology, 2020, 13, 50.
2. He, Y., Zhou, D., et al., Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies, J Hematol Oncol, 2020, 13: 103.

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