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    先導(dǎo)化合物 Lead Compound -生物名詞

    放大字體  縮小字體 發(fā)布日期:2005-05-13

    通過優(yōu)化藥用減少毒性和副作用可以使其轉(zhuǎn)變?yōu)橐环N新藥的化合物。一旦通過基因組學(xué)和藥理學(xué)方法發(fā)現(xiàn)和證實了一個有用的治療靶子,識別先導(dǎo)化合物是新藥開發(fā)的第一步。一般的,很多潛在化合物被篩選,大量緊密結(jié)合物被識別。這些化合物然后經(jīng)過一輪又一輪地增加嚴格性的篩選來決定它們是否適合于先導(dǎo)藥物優(yōu)化。一旦掌握了很多先導(dǎo)物,接下來就進入優(yōu)化階段,這需要做三件事:應(yīng)用藥物化學(xué)提高先導(dǎo)物對靶子的專一性;優(yōu)化化合物的藥物動力性能和生物可利用率;在動物身上進行化合物的臨床前的試驗。

    A compound that could potentially be converted to a new drug by optimizing its beneficial effects and minimizing its toxicity and side effects. Identifying lead compounds (typically by high-throughput screening) is the first step in the drug discovery process once a useful therapeutic target has been identified and validated through genomics and pharmacology. Typically, many potential compounds are screened (the primary screen) and numerous tight-binders (hits) are identified. These compounds are then taken through successive rounds of screening (secondary screens) of increasing stringency in order to determine their suitability for lead optimization. Once a handful of leads have been identified in this way, they are taken into lead optimization, which entails three things; the application of medicinal chemistry to improve the hit’s specificity to the target, optimization of the compound’s pharmacokinetics and bioavailability (ability to be metabolized by the body and to travel to its designated receptors in the afflicted cells and tissues), and the testing the compound in pre-clinical studies in animals.

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