運(yùn)用一小組化學(xué)構(gòu)建基因，以多種方式結(jié)合，用標(biāo)準(zhǔn)化學(xué)方法建立大的與醫(yī)藥相關(guān)的化合物的文庫(kù)，以用于新藥的篩選。組合化學(xué)與大規(guī)模篩選相結(jié)合用于識(shí)別與治療用靶蛋白結(jié)合的化合物即潛在新藥。最初的新的結(jié)合物稱(chēng)為"標(biāo)的"，標(biāo)的然后被優(yōu)化為"先導(dǎo)物"并最終發(fā)展成為真正的藥物。組合化學(xué)策略依賴(lài)于欲構(gòu)建文庫(kù)的大小、和多樣性，試劑的有效性和成本和化學(xué)合成的類(lèi)型。總體而言，有兩種形式的組合文庫(kù)合成，"液相"合成和"固相"合成，對(duì)后者來(lái)說(shuō)，化學(xué)反應(yīng)是與附在支持物（如：玻珠和柱子）上的一種或多種試劑發(fā)生的。這兩種文庫(kù)合成方法都有各自的優(yōu)、缺點(diǎn)；液相合成允許很多化學(xué)反應(yīng)進(jìn)行；然而所形成的文庫(kù)必然是液相混合物，必須能夠從組合混合物中區(qū)別單個(gè)化合物。固相合成的優(yōu)點(diǎn)是單個(gè)化合物在合成中是在空間上分開(kāi)的；然而必須發(fā)展新的化學(xué)反應(yīng)應(yīng)用于固相合成。

The use of a small set of chemical building blocks, combined together in multiple ways, using standard chemistries, to create large libraries of medicinally relevant compounds that may be screened for potential new drugs. Combinatorial chemistry is used in tandem with high-throughput screening to identify compounds that bind to a therapeutic target protein and are thus potential new drugs. Initial new binders are called “hits”; hits can then be optimized into “leads” for further development into bona fide drugs. Combinatorial chemistry strategies depend on the size and diversity of the library to be designed, the availability and cost of the reagents (building blocks), and the type of chemical syntheses being attempted. In general, two forms of combinatorial library synthesis exist, “liquid-phase” synthesis and “solid-phase” synthesis; in the latter the chemistries are performed with one or more of the reagents attached to an inert solid support such as a bead or column. Each of the two methods of library synthesis has its own advantages and disadvantages; Liquid-phase synthesis allows many more standard chemistries to be performed (most chemical synthesis steps have been developed for individual compound synthesis in the liquid phase); however, the resultant library is necessarily a mixture of compounds within the liquid, and deconvolution strategies must be applied to identify individual compounds from the combinatorial mixture. Solid-phase synthesis has the advantage that individual compounds are spatially separated during synthesis; however, novel chemistries must be developed in order to be useable in the solid phase.