Journal
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Volume 368, Issue 2, Pages 179-186Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.118.252361
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18K19400, 18H03190, 17K19487, 16K13044, 24390042]
- Japan Agency for Medical Research and Development (AMED)
- Adaptable and Seamless Technology Transfer Program through Target-driven R&D, the Japan Science and Technology Agency (JST)
- Platform for Drug Discovery, Informatics, and Structural Life Science of the Ministry of Education, Culture, Sports, Science and Technology, Japan
- JST CREST [JPMJCR17H3]
- Takeda Science Foundation
- Japan Society for the Promotion of Science (JSPS) [17J03990]
- Grants-in-Aid for Scientific Research [18H03190, 16K13044, 17J03990, 17K19487, 18K19400] Funding Source: KAKEN
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Claudin (CLDN) proteins, a tetra-transmembrane family containing over 20 members, have been identified as key structural and functional components of intercellular seals, tight junctions (TJs). CLDNs are involved in the barrier and fence functions of TJs. Loosening the TJ barrier is one strategy for increasing drug absorption and delivery to the brain. Due to aberrant CLDN expression, the TJ fence function is frequently dysregulated in carcinogenesis. In addition, CLDN-1 is a co-receptor for the hepatitis C virus. Together these characteristics indicate CLDNs as promising targets for drug development, and CLDN binders are potential candidates for delivering drugs, treating cancer, and preventing viral infection. Before 2008, a receptor-binding fragment of Clostridium perfringens enterotoxin was the only CLDN binder available. Since then, several challenges regarding the generation of monoclonal antibodies against CLDNs have been surmounted, leading to breakthroughs in CLDN-targeted drug development. Here, we provide an overview of the recent progress in technology using created CLDN binders-anti-CLDN monoclonal antibodies.
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