Small molecule agonists of toll-like receptors 7 and 8: a patent review 2014 - 2020

• Published in: Expert opinion on therapeutic patents Vol. 30; no. 11; p. 825
• Main Authors: Kieffer, Madeleine E, Patel, Akash M, Hollingsworth, Scott A, Seganish, W Michael
• Format: Journal Article
• Language: English
• Published: England 01.11.2020
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Drug Development; Humans; Immunity, Innate - drug effects; Neoplasms - drug therapy; Neoplasms - immunology; Patents as Topic; Toll-Like Receptor 7 - agonists; Toll-Like Receptor 8 - agonists; Virus Diseases - drug therapy; Virus Diseases - immunology; toll-like receptor 7; innate immune activation; toll-like receptor 8; immuno-oncology; Hepatitis B
• ISSN: 1744-7674
• DOI: 10.1080/13543776.2020.1825687

Toll-like receptors 7 and 8 (TLR7 and TLR8) are endosomal immune receptors that initiate an innate immune response and can facilitate activation of the adaptive immune system. Both preclinical and clinical studies have shown the downstream inflammatory response from TLR7 and TLR8 agonism results in preliminary efficacy for the treatment of cancer, viral infections, and for use as a vaccine adjuvant. This patent review covers recent developments in small molecule TLR7 and TLR8 agonists published between January 2014 - February 2020. We summarize relevant chemical scaffolds, observed structure-activity relationships, and where available, preliminary animal models, and clinical data. In the last 6 years, there has been significant progress in the optimization of novel TLR7 and TLR8 small molecule agonists. These novel compounds are currently being evaluated in the clinic for multiple antiviral and oncology indications. Clinical data from these trials will provide a clearer outlook on 1) the TLR7/8 engagement necessary to obtain the desired immune response, 2) safety margin improvement using directed delivery, and 3) potential synergistic effects with checkpoint inhibitor combination therapies.