Monoacylglycerol lipase (MAGL) terminates the signaling function of the endocannabinoid, 2-arachidonoylglycerol (2-AG). During 2-AG hydrolysis, MAGL liberates arachidonic acid, feeding the principal substrate for the neuroinflammatory prostaglandins. In cancer cells, MAGL redirects lipid stores toward protumorigenic signaling lipids. Thus MAGL inhibitors may have great therapeutic potential. Although potent and increasingly selective MAGL inhibitors have been described, their number is still limited. Here, we have characterized piperazine and piperidine triazole ureas that combine the high potency attributable to the triazole leaving group together with the bulky aromatic benzodioxolyl moiety required for selectivity, culminating in compound JJKK-048 that potently (IC50 < 0.4 nM) inhibited human and rodent MAGL. JJKK-048 displayed low cross-reactivity with other endocannabinoid targets. Activity-based protein profiling of mouse brain and human melanoma cell proteomes suggested high specificity also among the metabolic serine hydrolases.

No abstract

No abstract

Aims and objectives To describe advance care planning (ACP) for patients with cancer in palliative care from professionals' perspective. Background The number of patients with cancer is increasing. Palliative care should be based on timely ACP so that patients receive the care they prefer. Design A scoping review. Methods A systematic literature search was conducted in January 2019. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) checklist was used. The methodological quality of the studies was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal tools. Data were analysed with content analysis. Results Of 739 studies identified, 12 were eligible for inclusion. The settings were inpatient and outpatient facilities in special and primary care including oncology, palliative and hospice care. ACP consisted of patient‐oriented issues, current and future treatment, and end‐of‐life matters. The participants were nursing, medical or social professionals. ACP conversations rarely occurred; if they did, they took place at the onset, throughout and late in the cancer. Conclusions Professionals could not separate day‐to‐day care planning and ACP. ACP documentation was scattered and difficult to find and use. Professionals were unfamiliar with ACP, and established practices were lacking. ACP conversations mostly occurred in late cancer. Further research clarifying concepts and exploring the significance of ACP for patients and relatives is recommended. Relevance to clinical practice Our results support the use of ACP by a multidisciplinary team from the early stages of cancer as a discussion forum around patients' wishes and choices. We showed the need to raise professionals' awareness of ACP. Education and appropriate data tools for ACP are important as they may reduce reluctance and promote ACP use. This paper contributes to the wider global clinical community by pointing out the importance of standardising ACP contents and practices.