Investigation of Chiral Imidazoquinoline Based Heterocyclic Small Molecules on TLR7/8 Modulatory Activity
Abstract A library of chiral imidazoquinoline derivatives was synthesized and evaluated in HEK-Blue hTLR7 and hTLR8 reporter cell assays. The SAR study led to the identification of a highly potent novel dual TLR7/8 agonist 40 (EC50 78 nM for hTLR7 and 520 nM for hTLR8) and a TLR7/8 antagonist 31 (IC50 270 nM for hTLR7 and 320 nM for hTLR8). The research findings demonstrated the stereochemical dependence of TLR7/8 activity, possibly due to the different interactions of the two enantiomers in the TLR7/8 binding pocket.
Authors
- Deepender Kaushik
- Anshuman Dixit (ORCID: https://orcid.org/0000-0001-8063-7893)
- Binita Sihag
- Deepak B. Salunke (ORCID: https://orcid.org/0000-0002-1241-9146)
- Madhuri T. Patil
- Nikolai Petrovsky (ORCID: https://orcid.org/0000-0002-1580-5245)
- Yoshikazu Honda‐Okubo (ORCID: https://orcid.org/0000-0002-2872-8621)
- Pradeep K. Das
- Anjali Dadhwal
Institutions
- National Institute of Pharmaceutical Education and Research (IN)
- West Australian Sleep Disorders Research Institute (AU)
- Panjab University (IN)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2026-10-05
- DOI
- https://doi.org/10.1021/acsmedchemlett.6c00453
- Primary Topic
- Immune Response and Inflammation
- Type
- article
- Field-Weighted Citation Impact
- 0.00