Kinase-targeted cancer therapies: Progress, challenges and future directions

© 2018 The Author(s). The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies

Factors affecting the extraction of (poly)phenols from natural resources using deep eutectic solvents combined with ultrasound-assisted extraction

This is the final version. Available from Taylor & Francis via the DOI in this record. Replacing conventional solvents with deep eutectic solvents (DES) has shown promising effects on the extraction yield of (poly)phenols. DES can be combined with ultrasound-assisted extraction (UAE) to further increase the extraction efficiency of (poly)phenols from natural resources compared to conventional methods. This review discusses the factors associated with DES (composition, solvent-tosample ratio, extraction duration, and temperature) and UAE (ultrasound frequency, power, intensity, and duty cycle) methods that influence the extraction of (poly)phenols and informs future improvements required in the optimization of the extraction process. For the optimum (poly)phenol extraction from natural resources, the following parameters shall be considered: ultrasound frequency should be in the range of 20–50 kHz, ultrasound intensity in the range of 60–120 W/cm2 , ultrasound duty cycle in the range of 40–80%, ultrasound duration for 10–30 minutes, and ultrasound temperature for 25–50 �C. Among the reported DES systems, choline chloride with glycerol or lactic acid, with a solvent-to-sample mass ratio of 10–30:1 shown to be effective. The solvent composition and solvent-to-sample mass ratio should be selected according to the target compound and the source material. However, the high viscosity of DES is among the major limitations. Optimizing these factors can help to increase the yield of extracted (poly)phenols and their applications

A pilot dose-response study of the acute effects of haskap berry extract (Lonicera caerulea L.) on cognition, mood and blood pressure in older adults

Purpose Haskap (Lonicera caerulea L. or blue honeysuckle) is a plant native to the low-lying wet areas and mountains of Siberia and northeastern Asia, but is now cultivated in Canada. The dark blue berries are rich in anthocyanins, particularly cyanidin-3-O-glucoside. Previously, anthocyanin-rich fruits have been observed to benefit cognitive performance during the immediate postprandial period following a single acute dose. However, no study has currently examined the potential for haskap berries to influence cognitive performance. Here, we investigate the acute cognitive benefits of an anthocyanin-rich haskap berry extract. Methods A double-blind, counterbalanced, crossover intervention study compared the acute effects of three separate haskap berry extract doses, containing 100mg, 200mg, and 400mg anthocyanins, with a sugar-matched placebo. Participants were an opportunity sample of 20 older adults, aged 62-81 years. Measures of cognition, mood, and blood pressure were recorded at baseline and 1.5 hours postprandially. Results Compared to placebo, the 400mg dose elicited significantly lower diastolic blood pressure and heart rate. Both 200mg and 400mg doses elicited significantly higher word recall, with the 400mg dose also significantly improving word recognition scores, on an episodic memory task. However, mood, working memory and executive function task results were more equivocal. Conclusions The findings provide evidence for improvements in episodic memory and blood pressure following acute supplementation with haskap berry extract, with higher doses appearing most effective. The cognitive findings concur with previous literature that suggests episodic memory effects, and not executive function effects, are most prevalent in older adults following anthocyanin-rich berry supplementation. The blood pressure outcome is consistent with a vasodilatory mechanism of action