In vitro: TLR7-agonist-1 is a potent and selective Toll-like Receptor 7 (TLR7) agonist with a lowest effective concentration (LEC) of 0.4 μM in HEK293 cell. TLR7-agonist-1 is found to be selective for TLR7 over TLR8 with LEC of >100 μM for human TLR8. TLR7-agonist-1 demonstrates low inhibition across five CYP450 isozymes (IC50 >10 μM) and is also not a time dependent inhibitor of CYP450 3A4. TLR7-agonist-1 has limited inhibition of the hERG potassium ion channel 3H-dofetilide binding in vitro (IC50 >50 μM).
In vivo: TLR7-agonist-1 is found to be rapidly cleared in conjunction with our target profile. Both Cmax and AUC increase less than dose proportionally between 0.3 and 3 mg/kg and more than dose-proportionally between 3 and 10 mg/kg. TLR7-agonist-1 can induce an antiviral interferon stimulated gene (ISG) response without inducing an IFNα response at a low dose. TLR7-agonist-1 also induces a 2.7 log decrease in serum HBV viral load from 0.3 mg/kg, and a maximum 3.1 log decrease is observed for doses between 1 and 5 mg/kg.
|Cell lines||HEK293 cells|
|Preparation method||HEK293 cells are grown in culture medium (DMEM supplemented with 10% FCS and 2 mM Glutamine). Transfected cells are then detached with Trypsin-EDTA, washed in PBS and resuspended in medium to a density of 1.67×105 cells/mL. Thirty microliters of cells are then dispensed into each well in 384-well plates, where 10 μL of TLR7-agonist-1 in 4% DMSO is already present.|
|Concentrations||10 μL of TLR7-agonist-1 in 4% DMSO|
|Incubation time||6 h|
|Animal models||C57Bl/6 mice|
|Dosages||0.3, 1, 3, and 10 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||160 mg/mL in DMSO|
Identification and Optimization of Pyrrolo[3,2-d]pyrimidine Toll-like Receptor 7 (TLR7) Selective Agonists for the Treatment of Hepatitis B.
McGowan DC, et al. J Med Chem. 2017 Jul 27;60(14):6137-6151. PMID: 28671847.
Ceforanide is a new cephalosporin with antibacterial activity and has a longer elimination half-life than any currently available cephalosporin.
Inositol Nicotinate is a formulation of niacin, which is also called vitamin B3, an essential human nutrient.
ND-630 is an ACC inhibitor of human ACC1 and ACC2 with IC50 values of 2.1 and 6.1 nM, respectively.
|D-Luciferin potassium salt
D-Luciferin potassium salt is the substrate of luciferases that catalyze the production of light in bioluminescent insects.
|ZD 7114 hydrochloride
ZD 7114 is a selective β3 adrenergic receptor agonist.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.