Motolimod-VTX-2337-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMotolimodCat. No.: HY-13773CAS No.: 926927-61-9Synonyms: VTX-2337; VTX-378分式: CHNO分量: 458.6作靶点: Toll-like Receptor (TLR)作通路: Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验

2、DMSO : 50 mg/mL (109.03 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1805 mL 10.9027 mL 21.8055 mL5 mM 0.4361 mL 2.1805 mL 4.3611 mL10 mM 0.2181 mL 1.0903 mL 2.1805 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，

3、体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.45 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.45 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil

4、1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.45 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Motolimod是选择性的Toll样受体 8 (TLR8) 激动剂，EC50约为 100 nM。IC50 & Target EC50: 100 nM (TLR8) 1体外研究 Among the TLRs tested (TLR2, 3, 4, 5, 7, 8, and 9), Motolimod (VTX-2337) selectively activat

5、es TLR8.Motolimod stimulates the production of both TNF (EC50=14030 nM based on 10 donors) and IL-12(EC50=12030 nM based on 10 donors) in PBMCs. The EC50 value for MIP-1 induction is 60 nM forMotolimod 1.体内研究 Monkeys receive a subcutaneous injection of Motolimod (1 or 10 mg/kg), and plasma is collec

6、ted predose, 6,12, 24, and 96 h post-injection. For the 10 mg/kg dose, mean plasma levels of IL-1 increase from baselinelevels of 0.5 pg/mL, up to 9.122.7 ng/mL (p 2.PROTOCOLKinase Assay 1 Human embryonic kidney cells (HEK293) expressing TLR2, 3, 4, 5, 7, 8, or 9 are cultured in DulbeccosModified Ea

7、gles Media containing 4.5 g/L L-glucose and 10% FBS. The activity of specific TLR agonists isassessed using the secretory embryonic alkaline phosphatase (SEAP) reporter gene that is linked to NF-Bactivation in response to TLR stimulation. Measurement of SEAP activity using the Quanti-blue substratea

8、fter TLR agonist treatment is carried out similarly 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 PBMCs or purified NK cells are prepared, and the purity of NK cells is approximately 99%. NK cell-mediatedcytotoxicity is assessed by Calc

9、ein AM release from labeled target cells. In brief, PBMCs or purified NK cellsare cultured for 48 hours in RPMI medium in the presence of Motolimod (167 or 500 nM) before incubationwith target cells 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Anim

10、al Monkeys 2Administration 2 The male monkeys (2.9-4.9 kg) are housed individually (cage dimensions of 0.76 m wide0.74 m deep0.81m in height), but commingled periodically as part of the environmental enrichment program. The animals arealso given fruit, vegetable, or additional supplements as a form

11、of environmental enrichment, as well as givenvarious cage enrichment devices. Animals are given Certified Primate Diet, two times daily and water adlibitum. Motolimod is administered as a bolus subcutaneous (SC) injection in the intrascapular area at dosesof 1 and 10 mg/kg. Blood samples are collect

12、ed at baseline (pre-dose), and 6, 12, 24, and 96 h post injectionto monitor levels of IL-1 and IL-18 in the plasma using the human MAP v.1.6 inflammation panel.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedC

13、hemE户使本产品发表的科研献 J Exp Med. 2019 Feb 4;216(2):384-406. J Invest Dermatol. 2017 Feb;137(2):367-376. J Biol Chem. 2017 Feb 17;292(7):2805-2814. Nat Biomed Eng. 2018;2:578-588.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Lu H, et al. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res. 2012 Jan 15;18(2):499-509.2. Dietsch GN, et al. Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, IgnitesTumoricidal Natural Killer Cell Activity. PLoS One. 2016 Feb 29;11(2):e0