product name Motolimod (VTX-2337)
Description: Motolimod (also known as VTX-2337) is a small molecule, selective and potent Toll-like receptor (TLR) 8 agonist with EC50 of 100 nM, it displayes > 50-fold selectivity over TLR7. VTX-2337 is currently in clinical development as an immunotherapy for multiple oncology indications, including 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).
458.6
Formula
C28H34N4O2
CAS No.
926927-61-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 55 mg/mL (119.9 mM)
Water: <1 mg/mL
Ethanol: 15 mg/mL (32.7 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: VTX-2337 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. |
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| In Vivo | In an ovarian cancer mouse model, TX-2337 enhances the effect of pegylated liposomal doxorubicin (PLD); In male cynomolgus monkeys, VTX-2337 (1 or 10 mg/kg, subcutaneous injection) induced IL-1β and IL-18 production. |
| Animal model | |
| Formulation & Dosage | |
| References | Clin Cancer Res. 2012 Jan 15;18(2):499-509; J Clin Oncol 31, 2013 (suppl; abstr 3077). |
5-Deazaneplanocin A (hydrochloride)
