Discovery and Hit-to-Lead Optimization of Non-ATP Competitive MK2 (MAPKAPK2) Inhibitors
نویسندگان
چکیده
منابع مشابه
Hit discovery and hit-to-lead approaches.
Hit discovery technologies range from traditional high-throughput screening to affinity selection of large libraries, fragment-based techniques and computer-aided de novo design, many of which have been extensively reviewed. Development of quality leads using hit confirmation and hit-to-lead approaches present their own challenges, depending on the hit discovery method used to identify the init...
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The insulin-like growth factor-1 receptor (IGF-1 receptor) is a receptor tyrosine kinase, highly homologous to the insulin receptor. In contrast to the insulin receptor, which is mostly involved in metabolic pathways, the IGF-1 system plays a pivotal role in normal and neoplastic cell growth through anti-apoptotic, proliferative and metastatic pathways. Furthermore, IGF-1 receptor over-activati...
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The mammalian Target of Rapamycin (mTOR)-mediated signaling transduction pathway has been observed to be deregulated in a wide variety of cancer and metabolic diseases. Despite extensive clinical development efforts, the well-known allosteric mTOR inhibitor rapamycin and structurally related rapalogs have failed to show significant single-agent antitumor efficacy in most types of cancer. This l...
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Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our pri...
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A phenocopy is defined as an environmentally induced phenotype of one individual which is identical to the genotype-determined phenotype of another individual. The phenocopy phenomenon has been translated to the drug discovery process as phenotypes produced by the treatment of biological systems with new chemical entities (NCE) may resemble environmentally induced phenotypic modifications. Vari...
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ژورنال
عنوان ژورنال: ACS Medicinal Chemistry Letters
سال: 2011
ISSN: 1948-5875,1948-5875
DOI: 10.1021/ml200113y