Other
CN
EU
USA
Description: Motolimod (also known as VTX-2337) is a novel, selective and potent small molecule agonist of the Toll-like receptor (TLR) 8 with EC50 of 100 nM, it displays > 50-fold selectivity over TLR7 and has potential immunostimulating and anticancer activities. Motolimod is currently under clinical development as an immunotherapy for multiple oncology indications such as ovarian cancer and squamous cell carcinoma of the head and neck. TLR8 is located in the endosome where it functions in the recognition of foreign nucleic acids from intracellular pathogens. TLR8 has emerged as a potential target for anticancer immunotherapies.
References: Clin Cancer Res. 2012 Jan 15;18(2):499-509; J Clin Oncol 31, 2013 (suppl; abstr 3077).
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: VTX-2337 (Motolimod) stimulates the production of both TNFα with EC50 of 140 nM and IL-12 with EC50 of 120 nM in PBMCs. In monocytes and mDCs, VTX-2337 selectively induces the production of TNFα and IL-12 via NF-κB activation. VTX-2337 also stimulates IFNγ production from NK cells, augments the lytic function of NK cells and enhances ADCC.
Kinase Assay: The activity of specific TLR agonists is assessed using the secretory embryonic alkaline phosphatase (SEAP) reporter gene that is linked to NF-κB activation in response to TLR stimulation. Measurement of SEAP activity using the Quanti-blue substrate (InvivoGen) after TLR agonist treatment is carried out.
Cell Assay: PBMCs or purified NK cells are prepared as previously described, and the purity of NK cells was approximately 99%. NK cell–mediated cytotoxicity is assessed by Calcein AM release from labeled target cells. In brief, PBMCs or purified NK cells are cultured for 48 hours in RPMI medium in the presence of VTX-2337 (167 or 500 nmol/L) before incubation with target cells.
Purity ≥98%
COA
MSDS
VTX-2337 is a selective and potent TLR8 agonist that induces TNFα and IL-12 production. Clin Cancer Res. 2012 Jan 15;18(2):499-509.
VTX-2337 selectively induces the production of TNFα and IL-12 and activates NF-κB phosphorylation in monocytes and mDCs, but not pDCs. Clin Cancer Res. 2012 Jan 15;18(2):499-509.
VTX-2337 stimulates IFNγ production from NK cells. Clin Cancer Res. 2012 Jan 15;18(2):499-509.
VTX-2337 enhances the NK cell lytic activity and augments rituximab- and trastuzumab-mediated ADCC. Clin Cancer Res. 2012 Jan 15;18(2):499-509.
VTX-2337 enhances ADCC in donors with different SNP on FcγR3A. Clin Cancer Res. 2012 Jan 15;18(2):499-509.