Toll-like receptors (TLRs) play a crucial role in the innate immune system by recognizing pathogen-related molecular patterns from various microorganisms. Specifically, TLRs signal by recruiting specific adaptor molecules, leading to transcription factor NF- κ Activation of B and IRFs. Proper cellular localization of TLRs is important in signal regulation. Moreover, cell type-specific signals downstream of TLR determine specific innate immune responses. TLR is widely distributed in immune cells and other somatic cells. The expression and location of TLRs are responsive to specific molecules from pathogens or damaged host cells. Besides, the binding of ligands with TLR will activate specific intracellular signal cascade reactions, thus initiating a host defense response.

TLRs activation can affect the occurrence, progression, and treatment of cancer by regulating the inflammatory microenvironment. The number of evidence related to the function and expression of TLR in cancer cells has increased rapidly, indicating that TLR has a key relationship with chemotherapy resistance and tumorigenesis. Today, we will introduce a potent TLR1/TLR2 agonist, Diprovocim.

Diprovocim is a Potent TLR1/TLR2 Agonist.

From: Wang Y, et al. Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):E8698-E8706.

At first, Diprovocim elicits full agonist activity in human THP-1 cells (EC50=110 pM). Diprovocim stimulates the release of TNF-α from mouse macrophages (EC50=1.3 nM). Particularly, Diprovocim activates downstream MAPK and NF-κB signaling pathways. Diprovocim displayed strong adjuvant activity in mice, particularly abetting cellular immune responses.

Secondly, Diprovocim induces dose-dependent TNF production by THP-1 cells (EC50=110 pM). It is the same in human peripheral blood mononuclear cells (PBMC) (EC50=875 pM) and mouse peritoneal macrophages (EC50=1.3 nM) and bone marrow-derived dendritic cells (BMDC) (EC50=6.7 nM). In addition to TNF, Diprovocim induced IL-6 production by mouse BMDC. Diprovocim induced phosphorylation of IKKα, IKKβ, p38, JNK, and ERK, as well as degradation of IκBα.

Thirdly, Diprovocim with 10 mg/kg uses as an adjuvant and mixed with ovalbumin (OVA; 100 μg) by i.m. induces similar levels of serum OVA-specific IgG after 14 days. Obviously, Diprovocim mixed with ovalbumin before inoculation with B16-OVA cells immunizes significantly slows tumor growth rate.

Finally, Diprovocim is a potent TLR1/TLR2 agonist, that can activate cellular immune responses.


Ying Wang, et al. Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):E8698-E8706.