VTX-2337 Chemical Properties

Boiling point:

718.7±70.0 °C(Predicted)

Density 

1.19±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

Soluble in DMSO (up to at least 25 mg/ml)

form 

solid

pka

2.47±0.40(Predicted)

color 

Off-white or pale yellow

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

InChI

1S/C28H34N4O2/c1-3-13-31(14-4-2)28(34)24-17-23-12-11-22(18-25(23)30-26(29)19-24)20-7-9-21(10-8-20)27(33)32-15-5-6-16-32/h7-12,17-19,30H,3-6,13-16,29H2,1-2H3

InChIKey

CQAGPRVMJDWWEA-UHFFFAOYSA-N

SMILES

N4(CCCC4)C(=O)c1ccc(cc1)c2cc3c(cc2)C=C(C=C(N3)N)C(=O)N(CCC)CCC

Safety Information

WGK Germany 

WGK 3

Storage Class

11 - Combustible Solids

VTX-2337 Usage And Synthesis

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.

Uses

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.

in vivo

IC 50

TLR8

References

[1] HAILING LU. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC.[J]. Clinical Cancer Research, 2012, 18 2: 499-509. DOI:10.1158/1078-0432.ccr-11-1625
[2] HAILING LU. TLR8 agonist VTX-2337 enhances NKG2D-mediated cytotoxicity of NK cells[J]. Journal for Immunotherapy of Cancer, 2013, 49 1: P44-P44. DOI:10.1186/2051-1426-1-s1-p44
[3] Z. J. RUTNAM. Motolimod, a selective TLR8 agonist induces apoptosis in monocytic myeloid-derived suppressor cells (M-MDSC)[J]. Journal for Immunotherapy of Cancer, 2015, 3 1: P296-P296. DOI:10.1186/2051-1426-3-s2-p296
[4] R. FERRIS. Active8: a randomized, 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]. Journal for Immunotherapy of Cancer, 2014, 2 1: P69-P69. DOI:10.1186/2051-1426-2-s3-p69
[5] B. MONK. Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy[J]. Clinical Cancer Research, 2016, 23 1: 1955-1966. DOI:10.1158/1078-0432.ccr-16-1453
[6] G. DIETSCH. Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity[J]. PLoS ONE, 2016, 11 1. DOI:10.1371/journal.pone.0148764

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