Divneet Kaur’s research while affiliated with University of Nottingham and other places

Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as in vivo tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first in vivo validation of CaMK1D as a target for diabetes therapeutics.

The present invention relates to certain 4-(substituted aniline)-2-(substituted piperidin-1-yl)pyrimidine- -carboxamide compounds which may be useful in the treatment or prevention of a disease or medical condition mediated through signalling of CaMK1 isoforms. For example, such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers, metabolic diseases including type-2 diabetes, and/or immune-mediated disorders.