Tyrosine inhibitor

Milojkovic D et al (2009) Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia. Clin Cancer Res 15 7519-7527... 

Aza-indolin-2-one derivatives, (VI) prepared by Liang (6) were effective as HER-2 growth factor receptor tyrosine inhibitors and used in the treatment of uncontrolled cell proliferation associated with breast and ovarian cancers. 

Benzothiazole derivatives, (II), prepared by Scott (2) were useful as tyrosine inhibitor kinases and used in the treatment of hyperproliferative diseases, especially cancer. 

Isoflavones are found in Glycine max (soybean). Clinical research has demonstrated soy isoflavones to be effective in menstrual diseases. They have antioxidant activity also. Isoflavones belong to a group of compounds known as phyto-estrogens. The isoflavone content of soybean is 10 tO 20 times more than other plants. Genistein is a potent tyrosine inhibitor, whereas daidezein has antioxidant activity. Recently isoflavones have been investigated for hypolipidemic activity. 

Zhang and co-workers worked on the structure-based, computer-assisted search for low molecular weight, non-peptidic protein tyrosine phosphate IB (PTPIB) inhibitors, also using the DOCK methodology [89], They identified several potent and selective PTPIB inhibitors by saeening the ACD. 

Catecholamine biosynthesis begins with the uptake of the amino acid tyrosine into the sympathetic neuronal cytoplasm, and conversion to DOPA by tyrosine hydroxylase. This enzyme is highly localized to the adrenal medulla, sympathetic nerves, and central adrenergic and dopaminergic nerves. Tyrosine hydroxylase activity is subject to feedback inhibition by its products DOPA, NE, and DA, and is the rate-limiting step in catecholamine synthesis the enzyme can be blocked by the competitive inhibitor a-methyl-/)-tyrosine (31). 

Therapeutic Function Tyrosine hydroxylase Inhibitor Chetnicel Name tt-Methyl-L-tyrosine Common Name Metirosine Structural Formula ... 

Tyrosine Kinase Inhibitors/Receptor Associated Tyrosine Kinase Inhibitors (RTK-I)... 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

BCR-ABL tyrosine kinase that is essential for malignant transformation. Cytogenetic responses to IFN-a therapy were seen in 30-40% of the treated patients with complete responses in about 10%. Long term survival can therefore be expected in these patients. In 2000, the BCR-ABL tyrosine kinase inhibitor Imatinib has been introduced for CML therapy and meanwhile has proven more efficient than IFN-a therapy. 

Tyrosine Kinase Inhibitors Protein Kinase Inhibitors... 

Sorafenib is a multitargeted cancer therapy that inhibits VEGFR, PDGFR, KIT, fetal liver tyrosine kinase 3 (FLT-3), and the serine/threonine kinase RAF. RAF kinase is a key downstream effector of Ras in the MAPK/Ras signal-transduction pathway that has been linked to various cancers. Sorafenib is both a tyrosine kinase inhibitor and serine/threonine signal-transduction inhibitor. Sorafenib has been approved in renal cancer. 

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