Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome that expresses the constitutively activated tyrosine kinase Bcr-Abl; this enzyme causes hyper-proliferation of the stem cells and the consequent pathol. of the disease. Targeted inhibitors of Bcr-Abl have...
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2007 (v1)PublicationUploaded on: April 14, 2023
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2007 (v1)Publication
A review. Protein tyrosine kinases catalyze the transfer of phosphoryl groups from ATP to amino acids on proteins and play a fundamental role in signal transduction pathways in mammalian cells. In particular, Src and Src-family are non-receptor tyrosine kinases that regulate cell growth, differentiation, migration, adhesion and apoptosis. ...
Uploaded on: March 25, 2023 -
2007 (v1)Publication
Angiogenesis is a tightly regulated process that leads to the formation of new blood vessels in limited physiol. conditions, and can also occur under pathol. situations as retinopathies, arthritis, endometriosis and cancer. Enhanced angiogenesis is present in tumors that need new blood capillaries to grow, remove metabolic waste and transport...
Uploaded on: March 25, 2023 -
2008 (v1)Publication
Suggestions derived from a previous ligand-based ligand design approach and docking calcns. aimed at finding compd. with affinity toward Abl and mol. scaffolds previously untested as Abl inhibitors, led to the identification of com. available N-(thiazol-2-yl)-2-thiophene carboxamide derivs. with affinity in a cell-free assay up to low nanomolar...
Uploaded on: March 25, 2023 -
2007 (v1)Publication
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 homol. modeling techniques. The structures...
Uploaded on: April 14, 2023 -
2006 (v1)Publication
Abstract A computational protocol was applied to identify molecular scaffolds untested toward the c-Src tyrosine kinase. A combination of docking and dynamics calculations allowed us to build three-dimensional models of the complexes between Src and several of its known inhibitors. Interactions most contributing to activity of the inhibitors,...
Uploaded on: March 25, 2023 -
2006 (v1)Publication
We report the design and synthesis of a new class of piperazine-pyridazinone analogs. The arylpiperazine moiety, the length of the spacer, and the terminal mol. fragment were varied to evaluate their influence in detg. the affinity of the new compds. toward the α1-adrenergic receptor (α1-AR), α2-adrenergic receptor (α2-AR), and the 5-HT1A...
Uploaded on: April 14, 2023 -
2009 (v1)Publication
Docking simulations were used to predict the most favorable interaction between the T3151 mutated form of Abl (invariably assocd. with resistance to the tyrosine kinase inhibitor imatinib mesylate, IM) and C6-unsubstituted and substituted pyrazolo[3,4-d]pyrimidines previously found to be dual Src/Abl inhibitors. Two C6-unsubstituted (1 and 2)...
Uploaded on: May 13, 2023 -
2008 (v1)Publication
A series of substituted benzoylamino-2-[(4-benzyl)thio]-1,3,4-thiadiazoles has been discovered as potent Abl tyrosine kinase inhibitors. Mol. docking simulations on the Abl tyrosine kinase were conducted to rationalize the SAR of the synthesized inhibitors. The most active compd. identified from the enzymic screening (6a) showed interesting...
Uploaded on: April 14, 2023 -
2009 (v1)Publication
Pim1 belongs to a family of serine/threonine kinases, which is involved in the control of cell growth, differentiation, and apoptosis. Pim1 plays a pivotal role in cytokine signaling and is implicated in the development of a large number of tumors, representing a very attractive target for anticancer therapy. In this work, we applied a virtual...
Uploaded on: April 14, 2023