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학술발표회초록보기

초록문의 abstract@kcsnet.or.kr

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  • 08월 18일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제108회 대한화학회 학술발표회, 총회 및 기기전시회 안내 A practical methodology for identifying antinociceptive multi-target drugs

등록일
2011년 8월 5일 14시 54분 37초
접수번호
1549
발표코드
MEDI-6 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
목 16시 : 20분
발표형식
심포지엄
발표분야
의약화학 - New Technology in Drug Discovery
저자 및
공동저자
이두현
(주) 비보존 연구소, Korea
We review network pharmacology, multi-target drugs (or transient binding drugs) and introduce our progress in establishing a practical methodology for identifying antinociceptive multi-target drugs. The importance of phenotypic or efficacy screening has been emphasized as a methodology, but in vivo efficacy studies are labor intensive and time consuming. We have adopted a system of ex vivo efficacy screening using long-term potentiation in the dorsal horn of the rat spinal cord as a surrogate biomarker for neuropathic pain. We also set a known target for pain (GlyT2) as a bait target and identified a lead molecule from the public domain that has moderate potency at GlyT2. Lead optimization based on ex vivo efficacy identified multiple efficacious molecules in the rat model of neuropathic pain. One molecule was a moderately potent antagonist at three well-known pain targets (GlyT2, 5HT2A and P2X3), and pan screening showed no activity on major kinases, GPCRs and cardiac voltage-gated ion channels. The combined adminstration of a selective 5HT2A antagonist, MDL 11939, and a selective GlyT2 antagosnist, ORG-25543, produced a synergistic potentiation of the in vivo efficacy. These results suggest that efficacy screening for moderately potent molecules to a known target can be a reasonable approach in the search for multi-target drugs elucidating synergistic target combinations.

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