diprovocim-1

Diprovocim-1 is an agonist of the toll-like receptor 1/2 heterodimer.1It induces TNF-α release in THP-1 cells (EC50= 110 pM), an effect that can be inhibited by anti-TLR1 or anti-TLR2 antibodies. Diprovocim-1 (10 mg/kg) increases the production of ovalbumin-specific IgG1 in wild-type, but notTLR2-/-, mice sensitized to ovalbumin.2It also enhances anti-PD-L1 antibody-induced activation of cytotoxic T lymphocytes, reduction of tumor growth, and increases in survival in a B16/F10 murine melanoma model. 1.Morin, M.D., Wang, Y., Jones, B.T., et al.Diprovocims: A new and exceptionally potent class of toll-like receptor agonistsJ. Am. Chem. Soc.140(43)14440-14454(2018) 2.Wang, Y., Su, L., Morin, M.D., et al.Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in miceProc. Natl. Acad. Sci. U.S.A.115(37)E8698-E8706(2018)

Diprovocim-X (compound 35) 为有效的TLR1 TLR2激动剂，其对hTLR1 TLR2和mTLR1 TLR2的EC50值分别为0.14 nM和0.75 nM。此化合物在小鼠体内作为佐剂使用时，能有效激发适应性免疫反应。