Small molecule–mediated inhibition of protein function is the rational behind therapeutic efficacy of the majority clinically used drugs. In order for a drug to achieve pharmacologically relevant inhibition, efficient target engagement at high selectivity and specificity is necessary to obtain the desired therapeutic effect minimizing offtarget outcomes. Majority of small molecules approaches developed so far have failed in their attempt to reach clinical efficacy because of low selectivity and low specificity in achieving close to 100 % target inhibition. Recently, approaches that directly control cellular protein levels have opened the potential to accomplish a high grade of efficacy not imaginable with traditional small-molecule inhibitors. Research in this area has just started opening avenues to effectively degrade a cellular target of choice and will soon impact clinical efficacy.

小分子介导的蛋白质功能抑制是大多数临床使用药物治疗效果的合理依据。为了使药物实现药理学相关的抑制，必须以高选择性和特异性进行有效的靶标参与，以获得所需的治疗效果，从而最大限度地减少脱靶结果。迄今为止开发的大多数小分子方法都未能达到临床疗效，因为在实现接近 100% 的目标抑制方面的选择性和特异性低。最近，直接控制细胞蛋白质水平的方法开启了实现传统小分子抑制剂无法想象的高级功效的潜力。