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Researchers Find New Small Molecule Capable of Triggering the Immune System

April 20, 2015April 20, 2015
Patricia Silva PhDby Patricia Silva PhD

In News.

Researchers Find New Small Molecule Capable of Triggering the Immune System
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Researchers at the University of Colorado Boulder and Tsinghua University in China recently published in the journal Science Advances that a specific small molecule is capable of triggering an immune response, having potential biomedical applications for treating diseases such as Scleroderma. The study is entitled “Specific activation of the TLR1-TLR2 heterodimer by small-molecule agonists.”

The immune defense mechanism in vertebrates is divided into two groups: the innate immunity, which provides the first line of defense and an immediate response to infection or injury, and the adaptive immunity, which is characterized by a slow specific response through immune B and T cells. Toll-like receptors (TLRs) are elements that can detect pathogens through the recognition of pathogen-specific molecules and subsequent activation of the host’s immune responses. Stimulators or agonists of TLRs can trigger both the innate and the adaptive immune systems, having been exploited as potent vaccine adjuvants and anti-tumor agents.

Researchers have now identified a small molecule named CU-T12-9 [N-methyl-4-nitro-2-(4-(4-trifluoromethyl)phenyl)-1H-imidazol-1-yl)aniline] that can directly bind to TLR1 and TLR2, facilitating the formation of the heterodimer TLR1-TLR2 complex, and triggering a subsequent innate immune response.

“The TLR protein family has finally become a realistic target for drug developers,” said the study’s senior author Dr. Hang Hubert Yin in a news release. The research team believes that their work provides new insight into the signaling pathways of TLR1/2 and may also facilitate future therapeutic developments based on agonist molecules that can activate TLR1/2. “To the best of my knowledge, (…) our compound CU-T12-9 represents the first well characterized small molecule TLR1/2 agonist.”

Excessive TLR activation can, however, lead to an over-stimulation of the immune system, so a proper balance between activation and inhibition is necessary to optimize the immune response of patients to an anti-tumor drug or a new vaccine.

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The University of Colorado Boulder has filed a patent application for CU-T12-9 and also other TLR agents. The research team is currently looking for partnerships in the drug discovery field to further develop their TLR agents. CU-T12-9 in particular is currently licensed to Tocris Bioscience and EMD Millipore.

Another drug candidate targeting TLRs as a therapy for inflammatory disorders is TLR4 inhibitors, especially in disorders like neuropathic pain, a complex state of chronic pain where nerve fibers may be damaged or dysfunctional, and scleroderma, a rare chronic autoimmune disorder where the body’s own immune system attacks healthy tissue resulting in a hardening and tightening of the skin and connective tissue.

The research team believes that the development of small molecules targeting TLRs to trigger an immune system response can lead to the development of new vaccine adjuvants, anti-cancer agents and therapeutic drugs for inflammatory disorders such as scleroderma.

  • Author Details
Patricia Silva PhD
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Patricia Silva PhD
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Tagged CU-T12-9, immune system, Scleroderma, TLR, toll-like receptor.

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