VTX-2337

Description

Motolimod is an agonist of toll-like receptor 8 (TLR8). It increases the production of TNF-α and IL-12 in human peripheral blood mononuclear cells (PBMCs; EC₅₀s = 140 and 120 nM, respectively), monocytes, and myeloid dendritic cells. Motolimod also increases IFN-γ production in natural killer (NK) cells and increases cytolysis in K562 NK cell-sensitive leukemia cells when used at concentrations of 167 and 500 nM for 48 hours. It increases plasma levels of a group of human cytokines, including IL-6, IL-12p70, TNF-α, MCP-1, and MIP-1β, in NOD-scid IL2ry^null (NSG) mice reconstituted with human immune system (NSG-HIS) when administered at doses of 1.5 and 15 mg/m². Motolimod, when used in combination with pegylated liposomal doxorubicin (PLD), reduces tumor growth and increases tumor infiltration of monocytes and T cells in an ovarian cancer NSG-HIS mouse model.

The Uses of VTX-2337

Motolimod is an agonist of toll-like receptor 8 (TLR8) with potential immune-stimulating and antineoplastic properties. Motolimod is used in combination with PLD for the treatment of ovarian cancer.

References

1) Lu?et al.?(2012),?VTX-2337 is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC;?Clin. Cancer Res.?18?499 2) Lu?et al.?(2013),?TLR8 agonist VTX-2337 enhances NKG2D-mediated cytotoxicity of NK cells;?J. Immunother. Cancer?1?P44 3) Rutman?et al.?(2015),?Motolimod,a selective TLR8 agonist, induces apoptosis in monocytic myeloid-derived suppressor cells (M-MDSC);?J. Immunother. Cancer.?3?P296 4) Ferris?et al.?(2014),?Active8: a random, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with TLR8 agonist VTX-2337 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN);?J. Immunother. Cancer?2P69 5) Monk?et al.?(2017),?Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemo-Immunotherapy;?Clin. Cancer Res.?23?1955 6) Dietsch?et al.?(2016),?Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity;?PLoS One?11?e0148764