Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients coinfected and treated for both HIV-1 and hepatitis C virus (HCV), administration of ribavirin (RBV) may result in altered intracellular drug levels of nucleoside reverse transcriptase inhibitors through inhibition of inosine 5'-monophosphate dehydrogenase. Drug interactions between tenofovir and RBV were studied in vitro in order to provide insights into the safety of co-administration of tenofovir disoproxil fumarate (DF) and RBV in HCV/HIV-1-coinfected patients. In accordance with previous in vitro studies, strongly increased anti-HIV activity was observed when RBV was combined with didanosine (ddl). In contrast, low-level anti-HIV antagonism was observed when RBV was combined with either tenofovir or abacavir. Significantly stronger anti-HIV antagonism was observed when RBV was combined with either zidovudine, stavudine, emtricitabine or lamivudine. Thus, although tenofovir and ddl are both adenosine analogues, their in vitro interactions with RBV are markedly different. These results suggest a low potential for increased toxicity upon co-administration of tenofovir DF with RBV in patients.
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PMID:In vitro combination studies of tenofovir and other nucleoside analogues with ribavirin against HIV-1. 1586 29

Talaroflavone (1) and 1-deoxyrubralactone (2) are natural compounds isolated from cultures of a fungal strain derived from sea algae, and their structures were determined by spectroscopic analyses. Compound 2 is a novel rubralactone derivative, 6-hydroxy-8-methoxy-1-methyl-1,2,3a,9b-tetrahydrocyclopenta[c]isochromene-3,5-dione. These compounds selectively inhibited the activities of families X and Y of eukaryotic DNA polymerases (pols), and compound 2 was a stronger inhibitor than compound 1. The IC(50) values of compound 2 on rat pol beta, which is a pol of family X, and human pol kappa, which is a pol of family Y, were 11.9 and 59.8 microM, respectively. On the other hand, compounds 1 and 2 did not influence the activities of the other families of eukaryotic pols, such as family A (i.e., pol gamma) and family B (i.e., pols alpha, delta, and epsilon), and showed no effect even on the activities of plant pols alpha and beta, prokaryotic pols, and other DNA metabolic enzymes, such as calf primase of pol alpha, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerase I and II, T4 polynucleotide kinase, and bovine deoxyribonuclease I. This is the first report about the selective inhibitors of families X and Y of eukaryotic pols.
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PMID:1-deoxyrubralactone, a novel specific inhibitor of families X and Y of eukaryotic DNA polymerases from a fungal strain derived from sea algae. 1817 92

Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols eta, iota and kappa), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol iota activity was most strongly inhibited by compounds 1 and 2, with IC(50) values of 19.8 and 32.5 microM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol gamma), B-family (i.e., pols alpha, delta and epsilon) or X-family (i.e., pols beta, lambda and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol alpha, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.
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PMID:Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. 1922 84

We isolated a pol inhibitor from the cultured mycelia extract of a fungal strain isolated from natural salt from a sea salt pan in Australia, which was identified as 3-O-methylfunicone by spectroscopic analyses. This compound selectively inhibited the activities of mammalian Y-family DNA polymerases (pols) (i.e., pols eta, iota and kappa). Among these pols, human pol kappa activity was most strongly inhibited, with an IC(50) value of 12.5 microM. On the other hand, the compound barely influenced the activities of the other families of mammalian pols, such as A-family (i.e., pol gamma), B-family (i.e., pols alpha, delta and epsilon) or X-family (i.e., pols beta, lambda and terminal deoxynucleotidyl transferase), and showed no effect on the activities of fish pol delta, plant pols, prokaryotic pols and other DNA metabolic enzymes, such as calf primase of pol alpha, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I. This compound also suppressed the growth of two cultured human cancer cell lines, HCT116 (colon carcinoma cells) and HeLa (cervix carcinoma cells), and UV-treated HeLa cells exhibited lower clonogenic survival in the presence of inhibitor.
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PMID:3-O-methylfunicone, a selective inhibitor of mammalian Y-family DNA polymerases from an Australian sea salt fungal strain. 2009 3


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