With cutting-edge technology and extensive expertise, Alfa Cytology focuses on preclinical research of pancreatic cancer. Our service aims to decipher the intricate role of CD39 in pancreatic cancer progression and devise innovative strategies to inhibit its activity.
Introduction to CD39 and Its Signaling Pathway
CD39, also known as ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), is a typical ectonucleotidase with a catalytic site on the extracellular face. This glycoprotein consists of two transmembrane domains, an extracellular catalytic domain, and several glycosylation sites that are crucial for its stability and function. These domains are critical for the nucleotide hydrolysis process, and its primary function involves the conversion of extracellular ATP and ADP into AMP, ensuring precise regulation of extracellular nucleotide concentrations, which regulates purinergic signaling and modulating immune responses.
Fig. 1 Therapeutic regimens targeting CD39 alone or in combination with other strategies enhance antitumor immunity. (Guo S, et al, 2022)
CD39 Inhibitor Development for Pancreatic Cancer
Many tumors deplete immunostimulatory eATP by increasing CD39 expression to evade immune surveillance. Studies have shown that CD39 expression levels are increased in various tumors, including pancreatic cancer. CD39 inhibitors are therapeutic agents designed to block the activity of the enzyme CD39 and have therapeutic potential for diseases characterized by adenosine overproduction and immunosuppression, such as chronic infections and autoimmune diseases. CD39 inhibitors are currently being explored as potential treatments for pancreatic cancers with several promising candidates progressing through various stages of the drug development pipeline. Here are some examples:
| CD39 Inhibitor | Molecular Type | Target | Phase |
|---|---|---|---|
| TIDAL-01 (TTX-030) | Monoclonal antibody | CD39 | Phase I |
| AB680 | Small molecule inhibitor | CD39 | Phase I |
| SRF617 | Monoclonal antibody | CD39 | Phase I |
| BAY 1905254 | Small molecule inhibitor | CD39 | Preclinical |
Our Services
Alpha Cytology offers a comprehensive, customized service focused on the complex mechanisms of CD39-mediated immune evasion, with the aim of delivering potent inhibitors that have the potential to revolutionize the treatment of pancreatic cancer. Our expertise spans the spectrum from molecular characterization to functional testing, ensuring a robust pipeline for the discovery and validation of CD39 inhibitors.
Molecule Types for CD39 Inhibitor Development
Alfa Cytology offers comprehensive CD39 inhibitor development services for pancreatic cancer covering a wide range of molecule types, notably the following:
These inhibitors are designed to bind to the active site of CD39, blocking its enzymatic activity and preventing the conversion of ATP/ADP to AMP.
These are designed to bind to specific epitopes on CD39, blocking its activity or marking it for destruction by the immune system.
These contain Fab, scFv, and single-domain antibodies(sdAbs) that retain the ability to specifically bind to CD39. They offer advantages in terms of tissue penetration and reduced immunogenicity.
Designed to be used to inhibit CD39 expression at the gene level by targeting CD39 mRNA.
These include synthetic and mimetic peptides that mimic natural substrates or regulatory proteins, bind to CD39 and block its function.
CD39 Inhibitor Development Process
Target Identification and Validation
This step involves pinpointing CD39 as a target using genomic, proteomic, and bioinformatics approaches to understand its role in pancreatic cancer.
CD39 Inhibitor Design and Optimization
This phase focuses on refining the structure of identified inhibitors using computational modeling and medicinal chemistry to enhance their potency and selectivity.
Drug Screening
Identify potential CD39 inhibitors from libraries of small molecules, monoclonal antibodies, antibody fragments, siRNAs, miRNAs, and peptides by using high-throughput screening methods.
Comprehensive preclinical evaluation using in vivo and in vitro models for antitumor efficacy, DMPK/ADME, and safety testing of CD39 inhibitors.
Alfa Cytology is your partner of choice for groundbreaking preclinical research in pancreatic cancer. Focusing on CD39 inhibitors and other pancreatic cancer therapeutic targets, our services help researchers precisely target and develop highly specific and effective therapies to advance the field of precision oncology. With our extensive experience and state-of-the-art methodologies, we offer a comprehensive range of customized services to accelerate your R&D efforts. For inquiries or to learn more about how we can support your research project, please contact us.
Reference
- Guo S, et al. CD39–A bright target for cancer immunotherapy. Biomedicine & Pharmacotherapy. 2022, 151: 113066.
