- METHODS AND COMPOSITIONS FOR TREATING OBESITY, PREVENTING WEIGHT GAIN, PROMOTING WEIGHT LOSS, PROMOTING SLIMMING, OR TREATING OR PREVENTING THE DEVELOPMENT OF DIABETES
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The present invention relates to compositions and kits including a chemical uncoupler, such as tyrphostin 9 or precursor or a salt thereof, and compositions including a chemical uncoupler, such as tyrphostin 9 in combination with one or more therapeutic agents, for example, L-carnitine, which are useful, for example, in treating obesity, preventing weight gain, promoting weight loss/slimming, and/or treating or preventing the development of diabetes.
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Page/Page column 40; 41
(2016/01/25)
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- TX-1123: An antitumor 2-hydroxyarylidene-4-cyclopentene-1,3-dione as a protein tyrosine kinase inhibitor having low mitochondrial toxicity
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A series of 2-hydroxyarylidene-4-cyclopentene-1,3-diones were designed, synthesized, and evaluated with respect to protein tyrosine kinase (PTK) inhibition, mitochondrial toxicity, and antitumor activity. Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyrphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17, a potent antitumor tyrphostin. The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties, including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to protein tyrosine inase inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates that PTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AG17. Copyright
- Hori, Hitoshi,Nagasawa, Hideko,Ishibashi, Masaki,Uto, Yoshihiro,Hirata, Akihiko,Saijo, Kouichi,Ohkura, Kazuto,Kirk, Kenneth L,Uehara, Yoshimasa
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p. 3257 - 3265
(2007/10/03)
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- Tyrphostins I: Synthesis and Biological Activity of Protein Tyrosine Kinase Inhibitors
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A novel class of low molecular weight proteine kinase inhibitors is described.These compounds consitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain.These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor.The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 102-103 higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases.These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors.The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth.These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases.We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.
- Gazit, Aviv,Yaish, Pnina,Gilon, Chaim,Levitzki, Alexander
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p. 2344 - 2352
(2007/10/02)
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