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Adenosine is a naturally occurring purine nucleoside that has a wide variety of well-documented regulatory functions and physiological roles. Selective activation of the adenosine A1 receptor has drawn attention in drug discovery for the therapeutic effects on neural and cardiovascular disorders. We have developed a model of the human A1 adenosine receptor(More)
RET tyrosine kinase (TK) oncoproteins are potential targets for anticancer therapy. However, the search for novel RET inhibitors has been hampered by the lack of a 3D structure of the receptor. In this study, the "open" and the "closed" structure of the RET TK catalytic domain have been built by homology modeling techniques. The structures were validated by(More)
BACKGROUND Neuroblastoma (NB) is the second most common solid malignancy of childhood that usually undergoes rapid progression with a poor prognosis upon metastasis. The Src-family tyrosine kinases (SFKs) are a group of proteins involved in cancer development and invasiveness that seem to play an important role in the NB carcinogenesis. METHODS To(More)
The SGK1 kinase is pivotal in signal transduction pathways operating in cell transformation and tumor progression. Here, we characterize in depth a novel potent and selective pyrazolo[3,4-d]pyrimidine-based SGK1 inhibitor. This compound, named SI113, active in vitro in the sub-micromolar range, inhibits SGK1-dependent signaling in cell lines in a dose- and(More)
Recent data suggest that SRC family kinases (SFKs) could represent potential therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. Here, we assessed the effect of a recently developed selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on RMS cell lines. SI221, which showed to be mainly(More)
The serum/glucocorticoid-inducible kinase 1 (Sgk1) has demonstrated antiapoptotic function and the capability to regulate cell survival, proliferation, and differentiation. A pivotal role of Sgk1 in carcinogenesis and in resistance to anticancer therapy has been suggested. With the aim of identifying new Sgk1 modulators, 322 pyrazolo-pyrimidine derivatives(More)
The abnormal activity of Fyn tyrosine kinase has been shown to be related to various human cancers. Furthermore, its involvement in signaling pathways that lead to severe pathologies, such as Alzheimer's and Parkinson's diseases, has also been demonstrated, thus making Fyn an attractive target for the discovery of potential novel therapeutics for brain(More)
Molecular targeted therapies are based upon drugs acting on tumors by interfering with specific targets involved in growth and spread of cancer. Many targeted therapies were approved by Food and Drug Administration as standard treatment, others were introduced into preclinical or clinical studies on hematological malignancies (HMs). The development of(More)
Glioblastoma multiforme (GBM) is the most aggressive CNS tumor and is characterized by a very high frequency of clinical relapse after therapy and thus by a dismal prognosis, which strongly compromises patients survival. We have recently identified the small molecule SI113, as a potent and selective inhibitor of SGK1, a serine/threonine protein kinase, that(More)
Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile(More)