TLR3-IN-1 (CU CPT 4a) is a selective TLR3 inhibitor (IC50: 3.44 μM in RAW 264.7 cells). It can inhibit TLR3/dsRNA complex-mediated downstream signaling pathways and inhibit the production of TNF-α and IL-1β in whole cells.

Polyinosinic acid, a single-stranded homonucleic acid and a Toll-like Receptor 3 (TLR3) agonist, enhances the cellular immune response through TLR3 and TRIF. It holds potential applications in immune regulation [1].

Polyinosinic-polycytidylic acid potassium (Poly(I:C) potassium), a synthetic double-stranded RNA analog, serves as an agonist for toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I)-like receptors (RIG-I and MDA5), offering applications in immunotherapy. Its sodium variant enhances both innate and adaptive immune responses when used as a vaccine adjuvant, and is instrumental in modifying the tumor microenvironment. Additionally, Poly(I:C) potassium can directly induce apoptosis in cancer cells [1] [2] [3].

Poly(I:C):Kanamycin (1:1) sodium is a symmetric complex combining Poly(I:C) sodium, a synthetic double-stranded RNA analog acting as a TLR3 and RIG-I/MDA5 agonist, with Kanamycin, an antibacterial agent effective against both Gram-negative and positive bacteria by inhibiting translocation and causing miscoding on the 70S ribosomal subunit. Poly(I:C) sodium serves as a potent vaccine adjuvant, bolstering innate and adaptive immunity and prompting apoptosis in cancer cells [1] [2]. Meanwhile, Kanamycin exhibits significant efficacy against Mycobacterium tuberculosis, including drug-resistant strains, and Klebsiella pneumoniae, offering valuable insights for tuberculosis and pneumonia research [3] [4] [5] [6].

CRAMP (140-173) (mouse), the ortholog of the human LL-37 antimicrobial peptide, inhibits LPS-induced responses and does not colocalize with TLR3 in BEAS-2B cells [1].

NCI 126224, a toll-like receptor 4 (TLR4) antagonist, demonstrates selective inhibition of nitric oxide (NO) production in RAW 264.7 macrophages, triggered by the TLR4 agonist LPS (IC50 = 0.31 µM), as opposed to minimal effects on NO production induced by agonists for TLR7/8 (R-848), TLR1/2 (Pam3CSK4), and TLR3 (poly(I:C)). Nevertheless, it also effectively inhibits NO production initiated by the TLR2/6 agonist FSL-1 at an IC50 of 0.6 µM in the same cell line. Moreover, NCI 126224 suppresses LPS-induced NF-κB activity in BV-2 microglial cells and reduces LPS-triggered increases in IL-1β and TNF-α levels in RAW 264.7 macrophages with IC50 values of 5.92, 0.42, and 1.54 µM, respectively.

Enpatoran (M5049) hydrochloride is a potent and orally active dual inhibitor of TLR7/8 with IC50 values of 11.1 nM and 24.1 nM in HEK293 cells, respectively. This compound specifically inhibits TLR7 and TLR8, while showing no activity against TLR3, TLR4, and TLR9. Enpatoran hydrochloride has the ability to block both synthetic molecule ligands and natural endogenous RNA ligands. Additionally, it demonstrates excellent pharmacokinetic properties in vivo. Enpatoran hydrochloride can be a valuable tool for studying and modulating both innate and adaptive autoimmunity. [1]

SMU127 is an agonist of the toll-like receptor 1/2 (TLR1/2) heterodimer.1It induces NF-κB signaling in cells expressing human TLR2 (EC50= 0.55 μM) but not cells expressing human TLR3, -4, -5, -7, or -8 when used at concentrations ranging from 0.1 to 100 μM. SMU127 induces the production of TNF-α in isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations ranging from 0.01 to 1 μM.In vivo, SMU127 (0.1 mg/animal) reduces tumor volume in a 4T1 murine mammary carcinoma model. 1.Chen, Z., Cen, X., Yang, J., et al.Structure-based discovery of a specific TLR1-TLR2 small molecule agonist from the ZINC drug library databaseChem. Commun. (Camb.)54(81)11411-11414(2018)