CHEMICAL APPROACHES TO MODULATING THE IMMUNE RESPONSE: SYNTHESIS OF SMALL MOLECULE IMMUNE MODULATORS FOR AUTOIMMUNE DISEASES

Abstract

The autoimmune diseases are illnesses that arise as a result of aberrant activation of the immune system, chronic inflammation, and tissue damage. Small molecule immune modulators have shown great promise in giving cause for hope in therapeutic intervention through specific immune pathway modulation. These small molecules demonstrate advantages over biologics in terms of oral bioavailability, production cost, and tissue penetration. Recent advances in chemical synthesis and applications of small molecule modulators on innate immune receptors, such as Toll-like receptors (TLRs), nucleic acid sensing pathways, and inflammasomes, have also been reviewed in this paper. Particular attention has been given to TLR4 modulators, which are regarded as one of the most extensively studied TLRs concerning inflammatory diseases. Targeting of the cGAS-STING pathway and NLRP3 inflammasome have also gained much attention with respect to their therapeutic potentials in systemic lupus erythematosus (SLE), rheumatoid arthritis, and inflammatory bowel disease.

The modulators have differing modes of action such as inhibition for excessive immune activity or promotion of immune tolerance for the specific recipient. Advances in structure-based drug design and artificial intelligence-driven virtual screening for the discovery of new compounds have been comprehended in this review too. Several modulators, examples include Eritoran, TAK-242, and MCC950, have entered clinical trials, which highlights the promise of such approaches to clinical practice. However, there are certain challenges in specificity, off-target effects, and toxicity, which need to be overcome for an optimizing therapy. Future investigations will assess the effects of small molecule modifiers on pharmacokinetics despite focusing on the long-term efficacy and safety of these compounds in various patient demographics. Conclusively, this review captures the possibility of changing treatment perspectives for autoimmune and inflammatory diseases through the small molecules immune modulators..