122nd General Meeting of the KCS

Type Symposium
Area Current Trends in Drug Repositioning
Room No. Room 306B
Time THU 17:35-:
Code MEDI-5
Subject Non-systemic drug discovery using aminoalkylbenzothiazepine derivative
Authors Jaeho Yoo*, Seungin Kim1
Drug Discovery Center, durg discovery , Korea
1New drug research center, CJ HealthCare, Korea
Abstract Non systemic drug stay and absorb only in small and large intestines. It can’t absorb and means has merit during development because it doesn’t need human ADME(DDI), human QT study and preclinical in vitro ADME screening. We found aminoalkylbenzothiazepine derivative can be compelling Non-systemic drug for treatment of constipation. It strongly inhibit IBAT transporter. Ileum bile acid transports (IBAT) are involved in reabsorbing bile acids into liver and Inhibition of IBAT increases amount of bile acid in large intestine. Increasing bile acid help colonic motility and fecal secretion. Laxatives are used but cause serious side effects (diarrhea, abdominal pain) and resistance. Recent prescription medications still suffer from low efficacy and slow onset time as well as nausea, diarrhea and CV concern. We believe non-systemic drug can solve this problem. To find candidate compound, we used ligand based drug discovery strategy. We designed using sulfone motif and long alky chain. Such as polar and bulky properties can help to be non-absorbable. Compound A is oral bioavailable and has high potency in IBAT in vitro assay. To check efficacy, the experimental rats administered with the compounds A excreted feces within a reduced time and also showed a significantly higher percentage in the number of rats regarding showed excretion of feces within 10 hours, compared to the control rats administered with vehicle. This suggests that the compound A can effectively prevent or treat constipation Compound A exhibited potent and selective IBAT inhibition and effectively improved treatment constipation. These results warrant further investigation of compound A as a promising candidate for patient who needs treatment of constipation.
E-mail jh.yoo@cj.net