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Background: Focal adhesion kinase (Fak) is a cytoplasmic protein tyrosine kinase overexpressed and activated in different solid cancers; it has shown an important role in metastasis formation, cell migration, invasion and angiogenesis and consequently it has been proposed as a potential target in cancer therapy, particularly in a metastatic phase. In recent years, different investigations have highlighted the importance of new Fak inhibitors as potential anti-cancer drugs, but other studies evidenced its role in different pathologies related to the cardiac function or viral infection., Methods: An extensive bibliographic research (104 references) has been done concerning the structure of Fak, its importance in tumor development, but also in other pathologies currently under study. The compounds currently subjected to clinical studies were therefore treated using the appropriate databases. Finally, the main chemical scaffolds currently under preclinical investigation were analyzed, focusing on their molecular structures and on the activity structure relationships (SAR)., Results: At the moment, only a few reversible ATP-competitive inhibitors are under investigation in pre-clinical studies and clinical trials. Other compounds, with different chemical scaffolds, are investigated to obtain more active and selective Fak inhibitors. This mini-review is a summary of different Fak functions in cancer and other pathologies; the compounds today in clinical trials and the recent chemical scaffolds (also included in patents) giving the most interesting results are investigated. In addition, PROTAC molecules are reported., Conclusion: All reported results evidenced that additional studies are necessary to design and synthesize new selective and more active compounds, although promising information has been obtained from associations between Fak inhibitors and other different anti- cancer drugs. In addition, the other important roles evidenced, both at the nuclear level and in non-cancerous cells, make this protein an increasingly important target in pharmaceutical chemistry., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Janus kinases (JAKs) are a family of non-receptor tyrosine kinases, composed by four members, JAK1, JAK2, JAK3 and TYK2. JAKs are involved in different inflammatory and autoimmune diseases, as well as in malignancies, through the activation of the JAK/STAT signalling pathway. Furthermore, the V617F mutation in JAK2 was identified in patients affected by myeloproliferative neoplasms. This knowledge prompted researchers from academia and pharmaceutical companies to investigate this field in order to discover small molecule JAK inhibitors. These efforts recently afforded to the market approval of four JAK inhibitors. Despite the fact that all these drugs are pyrrolo[2,3-d]pyrimidine derivatives, many compounds endowed with different heterocyclic scaffolds have been reported in the literature as selective or multi-JAK inhibitors, and a number of them is currently being evaluated in clinical trials. In this review we will report many representative compounds that have been published in articles or patents in the last five years (period 2013-2017). The inhibitors will be classified on the basis of their chemical structure, focusing, when possible, on their structure activity relationships, selectivity and biological activity. For every class of derivatives, compounds disclosed before 2013 that have entered clinical trials will also be briefly reported, to underline the importance of a particular chemical scaffold in the search for new inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pyrrolo[2,3-d]pyrimidine nucleus is a deaza-isostere of adenine, the nitrogenous base of ATP, and is present in many ATP-competitive inhibitors of different kinases. In the last few years the number of articles and patents that have appeared involving this type of inhibitors has dramatically increased and some compounds have been approved for the treatment of inflammatory or myeloproliferative diseases. Other derivatives are currently being evaluated in clinical trials. This review deals with pyrrolo[2,3- d]pyrimidine derivatives active as kinase inhibitors that have been reported in the literature from 2011 to 2016, with a particular interest on the recently patented compounds. The molecules are classified depending on the inhibited kinase, focusing on their chemical structures., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)