Abstract: This disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and/or PFKFB4 has beneficial effect as well as neuroprotection.

Abstract: Methods and apparatus comprise a model to accurately assess and track changes in physical activity and locomotor patterns measured by an activity sensor such as accelerometer or step counter of mobile and wearable devices to evaluate the age, hazard rate or hazard ratio, frailty, obesity and type 2 diabetes status. The model is capable of detecting age-related and age-independent hazard rate or hazard ratio and other related parameters such as age, biological age, frailty, obesity and type 2 diabetes status that are detectable in activity sensor data acquired from freely moving subjects engaged in routine activities. The disclosed methods and apparatus have sufficient accuracy for practical implementation in personal and corporate wellness with readily available mobile devices such as personal smartphones and wristbands.