Independent Interdisciplinary Consultant, Oxford, UK.
Molecules. 2022 Nov 7;27(21):7624. doi: 10.3390/molecules27217624.
Faced with new and as yet unmet medical need, the stark underperformance of the pharmaceutical discovery process is well described if not perfectly understood. Driven primarily by profit rather than societal need, the search for new pharmaceutical products-small molecule drugs, biologicals, and vaccines-is neither properly funded nor sufficiently systematic. Many innovative approaches remain significantly underused and severely underappreciated, while dominant methodologies are replete with problems and limitations. Design is a component of drug discovery that is much discussed but seldom realised. In and of itself, technical innovation alone is unlikely to fulfil all the possibilities of drug discovery if the necessary underlying infrastructure remains unaltered. A fundamental revision in attitudes, with greater reliance on design powered by computational approaches, as well as a move away from the commercial imperative, is thus essential to capitalise fully on the potential of pharmaceutical intervention in healthcare.
面对新的、尚未满足的医疗需求，如果说制药发现过程表现不佳还不能完全被理解的话，那么这一说法是恰当的。受利润而非社会需求驱动，新药（小分子药物、生物制品和疫苗）的研发既没有得到适当的资金支持，也没有足够的系统性。许多创新方法仍未得到充分利用和重视，而主流方法则存在诸多问题和局限性。设计是药物发现的一个组成部分，虽然讨论得很多，但很少付诸实践。如果必要的基础结构保持不变，仅靠技术创新本身不太可能充分实现药物发现的所有可能性。因此，必须从根本上改变态度，更加依赖由计算方法驱动的设计，同时摆脱商业压力，从而充分利用药物干预在医疗保健中的潜力。
