Flavonoids as RTK inhibitors and potential anticancer agents. 2008

Florence Teillet, and Ahcene Boumendjel, and Jean Boutonnat, and Xavier Ronot
Laboratoire de Dynamique Cellulaire, EPHE, Laboratoire TIMC-IMAG, UMR-CNRS 5525, Université Joseph Fourier, Pavillon Taillefer, 38706 La Tronche Cedex, France.

Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D005419 Flavonoids A group of phenyl benzopyrans named for having structures like FLAVONES. 2-Phenyl-Benzopyran,2-Phenyl-Chromene,Bioflavonoid,Bioflavonoids,Flavonoid,2-Phenyl-Benzopyrans,2-Phenyl-Chromenes,2 Phenyl Benzopyran,2 Phenyl Benzopyrans,2 Phenyl Chromene,2 Phenyl Chromenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D017468 Receptors, Fibroblast Growth Factor Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity. FGF Receptor Complex,FGF Receptor Complexes,FGF Receptors,Fibroblast Growth Factor Receptors,Receptors, FGF,FGF Receptor,Fibroblast Growth Factor Receptor,Heparin-Binding Growth Factor Receptor,Heparin Binding Growth Factor Receptor,Receptor, FGF
D017479 Receptors, Platelet-Derived Growth Factor Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types. PDGF Receptors,Platelet-Derived Growth Factor Receptors,Receptors, PDGF,PDGF Receptor,Platelet-Derived Growth Factor Receptor,Platelet Derived Growth Factor Receptor,Platelet Derived Growth Factor Receptors,Receptor, PDGF,Receptors, Platelet Derived Growth Factor
D017526 Receptor, IGF Type 1 A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain. IGF Type 1 Receptor,IGF-I Receptor,Receptor, IGF-I,Receptor, Insulin-Like Growth Factor I,Receptor, Insulin-Like Growth Factor Type 1,IGF-1 Receptor,Insulin-Like-Growth Factor I Receptor,Receptor, IGF Type 1 alpha Subunit,Receptor, IGF Type 1 beta Subunit,Receptors, IGF-1,Receptors, Insulin-Like-Growth Factor I,IGF 1 Receptor,IGF I Receptor,IGF-1 Receptors,Insulin Like Growth Factor I Receptor,Receptor, IGF I,Receptor, IGF-1,Receptors, IGF 1
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein

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