Patent Highlights February-March 2018

摘要

Choline kinase is ubiquitously distributed in eukaryotes and catalyzes the first phosphorylation step of the Kennedy pathway for the de novo synthesis of phosphatidylcholine, the most abundant phospholipid in mammalian cellular membranes [1]. Fast-growing tissues, including tumors, have a high demand for this enzyme. Of the three isoforms (al, al, (3), expression of the a forms correlates with aggressiveness of many solid tumors, including pancreatic cancer [2] and T-cell lymphoma [3]. Choline kinase a inhibitors can inhibit tumor growth [4], and in fibroblast-like synoviocytes cultured from rheumatoid arthritis patients they suppress cell migration and resistance to apoptosis features that contribute to cartilage destruction [5]. The inventors present in vitro data for many new inhibitors that are up to 100-fold selective against the (3 isoform (IC50 values in the mid-nanomolar range for α and in the low micro molar range for (3), which is important because the fact that genetic choline kinase β deficiency causes muscular dystrophy suggests that its inhibition might lead to muscle and bone problems [6].