Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimitotic action of the systemic benzimidazole carbamate compound, benomyl, the basis for its fungitoxicity, was assessed in a mammalian system by selected biochemical endpoints of endometrial proliferation during decidualization in rats. The deciduoma, artificially induced on Day 4 of pseudopregnancy (PG), represents the maternal portion of the placenta that attains maximal growth between Days 9-11 PG. Deciduoma induction by surgical uterine trauma normally prolongs PG into the decidualization process. Measured endometrial parameters were the wet weight, protein for hypertrophy, DNA indicative of hyperplasia; enzymatic biomarkers- isocitrate dehydrogenase (ICDH) and the matrix metalloproteinases (MMPs); and serum progesterone which hormonally maintains decidual growth. Benomyl was administered by oral gavage in daily doses (500 mg/kg/rat in corn oil for 5 days, PG Days 5-9) and animals were sacrificed on PG Day 10. Benomyl caused significant reduction (P < 0.001) in endometrial wet weight, protein and DNA concentrations. ICDH activity was also significantly reduced (P < 0.01) following benomyl treatment. Of the two MMP species (72 and 92 kDa), whereas the 72 kDa was only slightly affected, the 92 kDa MMP was suppressed 2-3 fold by benomyl. Benomyl was without effect on the progesterone concentration. The findings suggest that during decidualization in rats, the anti-deciduogenic, antimitotic action of post-traumal benomyl treatment which occurred via the biochemical molecules (protein, DNA, ICDH and the MMPs) apparently was not mediated by progesterone.
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PMID:Biochemical characterization of benomyl inhibition on endometrial growth during decidualization in rats. 1002 46

Migration and invasion are two core processes during cancer metastasis, and several signaling pathways have been shown to be involved. A key regulator of metastasis is the mitogen-activated protein kinase signaling pathway. Here, we report that the small molecule, 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one, inhibited isocitrate dehydrogenase activity and had anti-metastatic effects in A549 human non-small-cell lung cancer cells. 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one induced sequential inactivation of the extracellular signal-regulated kinases and p38 signaling pathways, both representative mitogen-activated protein kinase family members. We also found that 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one suppressed the transcription factor c-Myc, a regulator of cancer metastasis. This led to selective attenuation of matrix metalloproteinase-2 and subsequent suppression of migration and invasion in A549 non-small-cell lung cancer cells. 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one also suppressed metastasis in H1299 non-small-cell lung cancer cells, suggesting that the effects of 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one are not limited to A549 non-small-cell lung cancer cells. We therefore propose that the antimetastatic effects of 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one are due to sequential inactivation of the extracellular signal-regulated kinases and p38 signaling pathways.
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PMID:IDH-Inhibiting Small Molecule DTDQ Inhibits Migration and Invasion of A549 Human Non-Small-Cell Lung Cancer Cells via Sequential Inactivation Of ERK and P38 Signaling Pathways. 2832 13