ABSTRACT
Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.
Subject(s)
Drug Discovery , Enzyme Inhibitors/pharmacology , Histone Demethylases/antagonists & inhibitors , Tranylcypromine/pharmacology , Cell Line, Tumor , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Histone Demethylases/genetics , Histone Demethylases/metabolism , Humans , Molecular Structure , Structure-Activity Relationship , Tranylcypromine/analogs & derivatives , Tranylcypromine/chemistrySubject(s)
Hemoglobins/analysis , Molecular Imprinting/methods , Polymers/chemistry , Animals , Cattle , Humans , Nanoparticles/chemistryABSTRACT
OBJECTIVE: To establish an animal model of myocardial ischemia with blood stasis syndrome in mini-swines. METHODS: An animal model of myocardial ischemia was established in mini-swines by oppressing the coronary artery through the expansion of inner layer of Ameroid constrictor and the Ameroid constrictor was implanted into the distal end of the initial part of the first branch of interventricular septum of ramus descendens anterior arteriae coronariae sinistrae. Dynamic observation of behavior changes, general health status and changes of hemorheological parameters in the mini-swines were made after operation. RESULTS: The coronary angiography showed that the stenosis rate in ischemic group was more than 75% four weeks after operation. Compared with before operation and sham-operated group, there were great changes of behavior, general health status, tongue color and hemorheological parameters in ischemic group (P<0.05). CONCLUSION: The animal model of myocardial ischemia with blood stasis syndrome in mini-swines was established successfully 4 weeks after operation. The pathological process in the animal model is similar to that in the patients with chronic myocardial ischemia. So this model can be adopted in the research of myocardial ischemia with blood stasis syndrome.
