[Drug innovation and reverse thinking].

Drug innovation involves an individual molecular operation, and every new molecular entity features a hard-duplicated track of R&D. The transformation from an active compound to a new medicine carries out almost in a chaotic system devoid of regularity and periodic alteration. Since new millennium the dominant position in drug innovation has been occupied by the first-in-class drugs, yet the number of launched follow-on drugs has been distinctly decreased. The innovation of first-in-class drugs is characterized by a high risk throughout the whole process. To achieve initiative and uniqueness of drug discovery, the strategy and method of the inverse thinking might be a feasible way, because the inertial and conformity thinkings in drug discovery normally lead to ensemble with similar drug category. However, the study from the flipside or opposite of things(e.g. targets or effects) brand new routes might be opened. This article is to describe the strategy of reverse thinking in drug discovery by some examples including opioid receptor antagonist eluxadoline, HSP90 activator, h ERG channel agonist, covalent drugs, and ultra-small drugs.