ArticleAsian-Australasian journal of animal sciences2020
In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor.
Article in Asian-Australasian journal of animal sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 9 citations in OpenAlex.
- Beryllium Sulfate-Induced Cellular Senescence via the IL-6/STAT3 Pathway to Promote Pulmonary Fibrosis.Journal of applied toxicology : JAT · 2026Article
- Folic acid deficiency exacerbates the inflammatory response of astrocytes after ischemia-reperfusion by enhancing the interaction between IL-6 and JAK-1/pSTAT3.CNS neuroscience & therapeutics · 2023Article
- The role of inflammation in autoimmune disease: a therapeutic target.Frontiers in immunology · 2023Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveInterleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized.
methodsLMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated.
resultsThe logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (Papp; 9.7×10-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and Cmax after oral administration (5 mg/kg) of LMT-28 were 302±209 h∙ng/mL and 137±100 ng/mL, respectively.
conclusionThese data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.
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