Rational modification of semaxanib and sunitinib for developing a tumor growth inhibitor targeting ATP binding site of tyrosine kinase
| Autor: | Baljit Kaur, Jagroop Kaur, Palwinder Singh |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Indoles Molecular model Clinical Biochemistry Substituent Pharmaceutical Science Antineoplastic Agents 01 natural sciences Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate Cell Line Tumor Drug Discovery Sunitinib medicine Humans Pyrroles Binding site Protein Kinase Inhibitors Molecular Biology Semaxanib Cell Proliferation chemistry.chemical_classification Binding Sites Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Protein-Tyrosine Kinases 0104 chemical sciences Molecular Docking Simulation 030104 developmental biology Enzyme chemistry Cell culture Molecular Medicine Drug Screening Assays Antitumor Tyrosine kinase medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 28:129-133 |
| ISSN: | 0960-894X |
| Popis: | Analysis of the crystal structure of tyrosine kinase in complexation with an ATP analogue, supplemented with the molecular docking studies of semaxanib and sunitinib in the ATP binding site of the enzyme enabled us to make design of a series of tyrosine kinase inhibitors. The combination of pyrrole and indolinone in one molecule and placement of appropriate substituent thereof made the molecule compatible for the hydrophobic sub-pocket of the enzyme. Screening of the compounds over 60 cell line panel of human tumor cell lines identified compound 3a that exhibited GI50 35 nM and 63 nM against MCF7 and MDA-MB-468 cell lines of breast cancer. |
| Databáze: | OpenAIRE |
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