A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target-ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public-private partnership.

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The epidemiology of adverse food reactions (AFRs), including the potentially life-threatening food allergy (FA), in Asia is unclear. AFR is believed to be less prevalent than in Caucasians. This study determines the prevalence, clinical features and risk factors for parent-reported AFR in Chinese pre-school children in Hong Kong. Children aged 2-7 yr living in Hong Kong were recruited through local nurseries and kindergartens to ascertain the occurrence and clinical spectrum of AFR and other atopic disorders. Subjects' parents answered a self-administered questionnaire that was modified and validated based on the International Study of Asthma and Allergy in Childhood. A total of 3827 children from 21 nurseries and kindergartens returned the study questionnaires, and information on AFR was analyzable for 3677 (96.1%) children. The prevalence rates of parent-reported AFR and parent-reported, doctor-diagnosed AFR were 8.1% and 4.6%, respectively, whereas 5.0% of pre-schoolers had doctor-diagnosed asthma. The six leading causes of AFR were shellfish (15.8%), egg (9.1%), peanut (8.1%), beef (6.4%), cow's milk (5.7%), and tree nuts (5.0%). When compared with children born and raised in Hong Kong, children born in mainland China (n = 253) had less parent-reported AFR (4.0% vs. 6.7%; p = 0.016). On logistic regression, parent-reported AFR was associated with younger age (p = 0.010), born in mainland China (p = 0.038), and AFR history in father (p = 0.001), mother (p < 0.001), siblings (p = 0.020), and paternal history of rhinitis (p = 0.044). This study shows that AFR is a common atopic disorder in Hong Kong pre-school children, and prevalence rates are comparable to the Caucasians.

Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System‐specific and drug‐specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration‐time profiles from 10 drugs in rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, and total brain tissue. These drugs, all small molecules, were selected to cover a wide range of physicochemical properties. The concentration‐time profiles for these drugs were adequately predicted across the CNS compartments (symmetric mean absolute percentage error for the model prediction was <91%). In conclusion, the developed PBPK model can be used to predict temporal concentration profiles of drugs in multiple relevant CNS compartments, which we consider valuable information for efficient CNS drug development.