Diprovocim (C09-1125-795)

Diprovocim is a potent TLR1/TLR2 agonist. Diprovocim elicits full agonist activity in human THP-1 cells (EC 50 =110 pM). Diprovocim stimulates the release of TNF-α from mouse macrophages (EC 50 =1.3 nM). Diprovocim activates downstream MAPK and NF-κB signaling pathway. Diprovocim displays strong adjuvant activity in mice, particularly abetting cellular immune responsesIn VitroDiprovocim (5 nM in THP-1 and 500 nM in mouse peritoneal macrophage; 15-120 mins) induces phosphorylation of IKKα, IKKβ, p38, JNK, and ERK, as well as degradation of IκBα in THP-1 cells and mouse peritoneal macrophages. Diprovocim (0.01-10000 nM; 4 hours) induces dose-dependent TNF production by THP-1 cells (EC 50 =110 pM) and human peripheral blood mononuclear cells (PBMC) (EC 50 =875 pM) and by mouse peritoneal macrophages (EC 50 =1.3 nM) and bone marrow-derived dendritic cells (BMDC) (EC 50 =6.7 nM). In addition to TNF, Diprovocim induced IL-6 production by mouse BMDC. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: THP-1 cells and mouse peritoneal macrophages Concentration: 5 nM in THP-1 and 500 nM in mouse peritoneal macrophages Incubation Time: 15, 30, 60, 120 mins Result: Induced phosphorylation of IKKα, IKKβ, p38, JNK, and ERK, as well as degradation of IκBα.In VivoDiprovocim (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. Diprovocim (10 mg/kg; i.m.) mixed with ovalbumin (OVA; 100 μg) before inoculation with B16-OVA cells immunizes significantly slows tumor growth rate but failed to prolong survival relative to OVA alone after 7 days. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: WT or Tlr2 −/− C57BL/6J miceDosage: 10 mg/kg Administration: IM Result: Induced similar levels of serum OVA-specific IgG, which were highly elevated compared with levels induced by immunization with OVA plus vehicle by i.m. with 100 μg OVA mixed with this drug.Form:SolidIC50& Target:TLR1|TLR2|p38 MAPK|NF-κB. Specification: 0.98 Molecular Formula: C56H56N6O6 Molecular Weight: 909.08 PubChem CID: 137553173 Isomeric SMILES: C1[C@@H]([C@H]1NC(=O)[C@@H]2CN(C[C@H]2C(=O)N[C@H]3C[C@@H]3C4=CC=CC=C4)C(=O)C5=CC=C(C=C5)C(=O)N6C[C@H]([C@@H](C6)C(=O)N[C@H]7C[C@@H]7C8=CC=CC=C8)C(=O)N[C@H]9C[C@@H]9C1=CC=CC=C1)C1=CC=CC=C1