Profile and Molecular Modeling of 3-(Indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1<i>H</i>-pyrrole-2,5dione (<b>1</b>) as a Highly Selective VEGF-R2/3 Inhibitor

Peifer, Christian; Krasowski, Agata; Hämmerle, Nina; Kohlbacher, Oliver; Dannhardt, Gerd; Totzke, Frank; Schächtele, Christoph; Laufer, Stefan

doi:10.1021/jm0609871

Cited by 28 publications

(22 citation statements)

References 47 publications

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“…Many groups choose to concentrate on kinases in the same family and, therefore, with similar ATP binding site sequences [114,148]. Another approach is to measure effects on functionally related kinases, as inhibiting more than one enzyme on the same signalling pathway may make a significant difference to the action of a drug [51].…”

Section: The Importance Of Determining Selectivitymentioning

confidence: 99%

Measuring and interpreting the selectivity of protein kinase inhibitors

2009

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Protein kinase inhibitors are a well-established class of clinically useful drugs, particularly for the treatment of cancer. Achieving inhibitor selectivity for particular protein kinases often remains a significant challenge in the development of new small molecules as drugs or as tools for chemical biology research. This review summarises the methodologies available for measuring kinase inhibitor selectivity, both in vitro and in cells. The interpretation of kinase inhibitor selectivity data is discussed, particularly with reference to the structural biology of the protein targets. Measurement and prediction of kinase inhibitor selectivity will be important for the development of new multi-targeted kinase inhibitors.

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Section: The Importance Of Determining Selectivitymentioning

confidence: 99%

Measuring and interpreting the selectivity of protein kinase inhibitors

2009

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“…Molecular modelling studies on d-annulated benzazepinones as VEGF-R2 kinase inhibitors using docking and 3D-QSAR used to be binding site of most inhibitors 9 . Recently, many investigations on small molecule inhibitors with diverse pharmacophores as antiangiogenic agents targeting at VEGF-R2 have been carried out.…”

Section: Original Articlementioning

confidence: 99%

Molecular modelling studies on d-annulated benzazepinones as VEGF-R2 kinase inhibitors using docking and 3D-QSAR

Lan

Sun

Chen

et al. 2010

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Authors also performed docking studies with a different TK, namely FAK, aimed at explaining selectivity of (89) towards VRGFR-2. The interaction pattern of (89) with the two TKs is similar, but in FAK the indole moiety is twisted out of the hydrophobic pocket it occupies in VEGFR-2, thus explaining the enzyme selectivity data [190,191].…”

Section: Miscellaneous Compoundsmentioning

confidence: 99%

Antiangiogenic Agents: an Update on Small Molecule VEGFR Inhibitors

Schenone¹,

Bondavalli²,

Botta

2007

CMC

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Angiogenesis is a tightly regulated process that leads to the formation of new blood vessels sprouting from pre-existing microvasculature and occurs in limited physiological conditions or under pathological situations such as retinopathies, arthritis, endometriosis and cancer. Blockade of angiogenesis is an attractive approach for the treatment of such diseases. Particularly in malignancies, antiangiogenic therapy should be less toxic in comparison with conventional treatments such as chemotherapy, as angiogenesis is a process relatively restricted to the growing tumor. Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis and exerts its cellular effects mainly by interacting with two high-affinity transmembrane tyrosine kinase receptors: VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). It has been proven that inhibition of VEGF receptor activity reduces angiogenesis. For these reasons, the inhibition of VEGF or its receptor signalling system is an attractive target for therapeutic intervention. The most studied and developed inhibitors are monoclonal antibodies that neutralize VEGF, ribozymes, and small molecule VEGFR kinase inhibitors. Many important reviews dealing with VEGF-induced angiogenesis and its inhibition through the block of VEGF receptors have been reported, especially from a biological point of view. Here, we will review small synthetic VEGFR inhibitors that have appeared in literature in the last few years, focusing our attention on their medicinal chemistry in terms of chemical structure, mechanisms of action and structure-activity relationships. In fact, there have been an increased number of tyrosine kinase inhibitors in the most recent literature reports; their biological profile is extremely interesting and could be of great importance to medicinal chemists working in this area in improving their efficacy.

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Profile and Molecular Modeling of 3-(Indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5dione (1) as a Highly Selective VEGF-R2/3 Inhibitor

Cited by 28 publications

References 47 publications

Measuring and interpreting the selectivity of protein kinase inhibitors

Measuring and interpreting the selectivity of protein kinase inhibitors

Molecular modelling studies on d-annulated benzazepinones as VEGF-R2 kinase inhibitors using docking and 3D-QSAR

Antiangiogenic Agents: an Update on Small Molecule VEGFR Inhibitors

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