2.7.7.6 (NH4)2SO4 - 399 2.7.7.6 (S)-2-((1-amino-1-oxo-3-phenylpropan-2-ylamino)methyl)-3-(4-amino phenoxy)-5-methoxy phenyl acetate - 77929 2.7.7.6 (S)-2-((1-amino-1-oxo-3-phenylpropan-2-ylamino)methyl)-5-methoxy-3-(4-nitrophenoxy)phenyl acetate - 77927 2.7.7.6 (S)-2-((1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)methyl)-3-(4-aminophenoxy)-5-methoxyphenyl acetate - 77928 2.7.7.6 (S)-2-((1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-ylamino)methyl)-5-methoxy-3-(4-nitrophenoxy)phenyl acetate - 77926 2.7.7.6 1,3-dimethoxy-5-(4-nitrophenoxy) benzene - 77922 2.7.7.6 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine i.e. ECyd, TAS-106, a antitumor ribonucleoside that inhibits RNA polymerase, acts synergistically in inhibiting A-549 cancer cell growth and in tumor growth in vivo. The compound also inhibits the checkpoint-associated protein, the expression of Chk1 protein and the phosphorylation of Chk1 and Chk2, antitumour effects in combination with cisplatin, overview 155594 2.7.7.6 1-[2-[3-(4-Chloro-3-trifluoromethylphenyl)ureido]-4-trifluoromethyl phenoxy]-4,5-dichlorobenzene sulfonic acid - 16023 2.7.7.6 2'-C-ethynyl-7-deaza-ATP causes immediate chain termination 256911 2.7.7.6 2'-C-Me-ATP causes immediate chain termination 256910 2.7.7.6 2,4-dimethoxy-6-(4-nitrophenoxy) benzaldehyde - 77923 2.7.7.6 2-([[(1S)-2-amino-1-(4-hydroxybenzyl)-2-oxoethyl]amino]methyl)-5-methoxy-3-(4-nitrophenoxy)phenyl acetate - 76539 2.7.7.6 2-acetyl-3-hydroxy-5-methoxyphenyl acetate - 76545 2.7.7.6 2-acetyl-5-methoxy-3-(4-nitrophenoxy)phenyl acetate - 76546 2.7.7.6 2-formyl-5-methoxy-3-(4-nitrophenoxy)phenyl acetate - 77925 2.7.7.6 2-hydroxy-4-methoxy-6-(4-nitrophenoxy) benzaldehyde - 77924 2.7.7.6 3'-dATP causes immediate chain termination 2008 2.7.7.6 3'-ethynylcytidine-5'-triphosphate i.e. ECTP, competitive inhibition in the presence of isolated nuclei from FM3A mouse tumor cells 155595 2.7.7.6 4-[2-([[(1S)-2-amino-1-(4-hydroxybenzyl)ethyl]amino]methyl)-5-methoxy-3-(2-oxopropyl)benzyl]benzaldehyde - 76647 2.7.7.6 6,10,6'-tri-O-tert-butyldimethylsilyl-6-epi-catalpol - 212286 2.7.7.6 ABI-1131 - 135624 2.7.7.6 actinomycin - 5512 2.7.7.6 actinomycin D - 2941 2.7.7.6 alpha-amanithin - 51515 2.7.7.6 alpha-Amanitin alpha-amanitin inhibits Pol II by trapping the wedged trigger loop and shifted bridge helix, thereby stabilizing a conformation of the elongation complex that apparently represents a translocation intermediate 15619 2.7.7.6 alpha-Amanitin the potent Sc RNAP II inhibitor binds to a ternary elongation complex with an open wedged conformation of the trigger loop 15619 2.7.7.6 amanitin - 112983 2.7.7.6 ara-ATP causes partial chain termination 9102 2.7.7.6 aureolic acid - 113798 2.7.7.6 B2 RNA the about 180-nt B2 RNA potently represses mRNA transcription by binding tightly to RNA polymerase II and assembling with it into complexes on promoter DNA, where it keeps the polymerase from properly engaging the promoter DNA. The C-terminal domain of the largest Pol II subunit is not involved. B2 RNA binds Pol II and assembles into complexes at promoters. Binding site anaylsis usig Pol II peptides, binding structure, and mechanism of transcriptional repression by B2 RNA, detailed overview 172251 2.7.7.6 breast cancer susceptibility gene 1 BRCA1, inhibits RNA pol III via inhibition of the essential transcription factor TFIIIB, mechanism, overview. BRCA1 is a tumor suppressor playing a role in DNA repair, cell cycle regulation, apoptosis, genome integrity, and ubiquitination, and it BRCA1 has a conserved N-terminal RING domain, an activation domain 1, AD1, and an acidic C-terminal domain, BRCA1 C-terminal region. Interaction with TFIIIB occurs via the BRCA1 C-terminal region domain of Fcp1p, an RNA polymerase II phosphatase. RNA pol III inhibition involves the TFIIB family members Brf1 and Brf2, overview 155597 2.7.7.6 CBR-703 - 135629 2.7.7.6 CBR703 the IC50s values are significantly decreased with template Kool NC-45, or increased with template poly(dA-dT) 172252 2.7.7.6 Cdc14 a protein phosphatase required for nucleolar segregation and mitotic exit4, inhibits RNA polymerase I, the phosphatase activity of Cdc14 is required for Pol I inhibition in vitro and in vivo involving nucleolar exclusion of Pol I subunits 59381 2.7.7.6 chromomycin - 113200 2.7.7.6 Cinerubin B - 92919 2.7.7.6 cisplatin a single cisplatin 1,2-d(CG) intrastrand cross-link or a single cisplatin 1,3-d(GTG) intrastrand cross-link is a strong block to the enzyme. The efficiency of the block at a cisplatin 1,2-d(GG) intrastrand cross-link is similar in several different nucleotide sequence contexts. Some blockage is also observed when the single cisplatin 1,3-d(GTG) intrastrand cross-link is located in the non-transcribed strand. Cisplatin-induced lesions in the transcribed DNA strand constitute a strong physical barrier to RNA polymerase progression 1397 2.7.7.6 corallopyronin inhibition is not affected by template Kool NC-45 172253 2.7.7.6 corallopyronin A - 135626 2.7.7.6 Cordycepin triphosphate - 43941 2.7.7.6 d(Ap4C) d(Ap4T), d(Ap4C) and d(Ap4G) inhibit the incorporation of dATP into DNA less effectively than d(Ap4T), d(Tp4T) and d(Tp4C) the dTTP incorporation 127470 2.7.7.6 d(Ap4G) d(Ap4T), d(Ap4C) and d(Ap4G) inhibit the incorporation of dATP into DNA less effectively than d(Ap4T), d(Tp4T) and d(Tp4C) the dTTP incorporation 127471 2.7.7.6 d(Ap4T) d(Ap4T), d(Ap4C) and d(Ap4G) inhibit the incorporation of dATP into DNA less effectively than d(Ap4T), d(Tp4T) and d(Tp4C) the dTTP incorporation 35196 2.7.7.6 d(Tp4C) d(Ap4T), d(Ap4C) and d(Ap4G) inhibit the incorporation of dATP into DNA less effectively than d(Ap4T), d(Tp4T) and d(Tp4C) the dTTP incorporation 35198 2.7.7.6 d(Tp4T) d(Ap4T), d(Ap4C) and d(Ap4G) inhibit the incorporation of dATP into DNA less effectively than d(Ap4T), d(Tp4T) and d(Tp4C) the dTTP incorporation 35197 2.7.7.6 daunomycin - 10631 2.7.7.6 DNA various DNA lesions significantly affect the efficiency and fidelity of RNA synthesis. DNA modifications that disrupt correct base-pairing can strongly inhibit transcription and increase nucleotide misincorporation by RNAP. The universal transcription factor GreA and Deinococcus-specific factor Gfh1 stimulate RNAP stalling at various DNA lesions, depending on the type of the lesion and the presence of Mn2+ ions 293 2.7.7.6 echinomycin - 93313 2.7.7.6 Eruticulomycin A - 98293 2.7.7.6 Ethidium bromide - 2021 2.7.7.6 etnangien from the myxobacterium Sorangium cellulosum, a poly-unsaturated 22-membered polyketide macrolide, inhibits bacterial RNA polymerase, shows no cross-resistance to rifampicin 12067 2.7.7.6 etnangien from the myxobacterium Sorangium cellulosum, a poly-unsaturated 22-membered polyketide macrolide, inhibits bacterial RNA polymerase, shows no cross-resistance to rifampicin, poor inhibition 12067 2.7.7.6 etnangien from the myxobacterium Sorangium cellulosum, a poly-unsaturated 22-membered polyketide macrolide, inhibits bacterial RNA polymerase, poor inhibition of the yeast enzyme 12067 2.7.7.6 etnangien methyl ester - 12068 2.7.7.6 etnangien methyl ester weak inhibition 12068 2.7.7.6 etnangien methyl ester very weak inhibition 12068 2.7.7.6 etoposide treatment with 0.02 mM etoposide leads to a transient inhibition of rRNA synthesis 774 2.7.7.6 Exotoxin of Bacillus thuringiensis - 99102 2.7.7.6 GE-23077-A - 135632 2.7.7.6 GE-23077-B - 135633 2.7.7.6 heparin - 227 2.7.7.6 Isoquinocyclin - 98009 2.7.7.6 KCl above 10 mM 79 2.7.7.6 lipiarmycin - 62691 2.7.7.6 ML-60218 treatment of A-549 cells with the Pol III inhibitor ML-60218 decreased the cytosolic RNA:DNA hybrid staining 213903 2.7.7.6 MnCl2 in presence of 10 mM MgCl2 307 2.7.7.6 additional information no inhibition by NEM and iodoacetamide 2 2.7.7.6 additional information no inhibition by epigallocatechin gallate 2 2.7.7.6 additional information no inhibition by ent-16-ketobeyeran-19-oic acid, i.e. isosteviol, and related compounds 2 2.7.7.6 additional information despite relatively high overall sequence and structural homology between bacterial and mammalian core RNAP enzymes, there are sufficient differences between the enzyme classes for exploitation in the discovery of selective bacterial inhibitors 2 2.7.7.6 additional information gamma irradiation leads to a transient inhibition of rRNA synthesis, but Pol I transcription is not blocked by DNA damage itself, but by the action of DNA repair enzymes 2 2.7.7.6 additional information inactivation of RNase P, by knockdown of RNase P subunits Rpp21, Rpp29 or Rpp38 by RNA interference, reduces the level of nascent transcription by Pol I, and more considerably that of Pol III, e.g. causing marked reduction in transcription of rDNA by Pol I 2 2.7.7.6 additional information oncogenes and tumor suppressors control Pol I transcription, overview. Development of drugs that target the Pol I transcription machinery at different points, overveiw 2 2.7.7.6 additional information synthesis of simplified etnangien analogues and analysis of their antimicrobial activities, overview 2 2.7.7.6 additional information no inhibition of RNA transcription by RECQL5 helicase-deficient point mutant RECQL5D157A, and another human RECQ family helicase, RECQL1 2 2.7.7.6 additional information Top1 inhibition favors Pol II escape from a promoter-proximal pausing site of the human HIF-1alpha gene in living cells. Top1 inhibition can trigger a transcriptional stress, involving antisense transcription and increased chromatin accessibility, which is dependent on cdk activity and deregulated Pol II pausing 2 2.7.7.6 additional information structure-based design of inhibitors with rifampicin as template, inhibitory potencies and binding mechanism via specific hydrogen-bonding sites involving residues Q390, F394, R405, Q567 and Q633, overview 2 2.7.7.6 additional information a relatively short DNA region, lost in up2DELTA mutant and located immediately upstream of the URA2 initiator, impairs URA2 transcription by preventing RNA polymerase II from progressing towards the URA2open reading frame 2 2.7.7.6 additional information the use of dsDNA templates containing classical promoters has only a negligible effects on the potency of enzyme inhibitors 2 2.7.7.6 additional information POLRMT is an off target for antiviral ribonucleoside analogues, unique mechanisms of mitochondrial transcription inhibition, overview 2 2.7.7.6 additional information FLiZ antagonize sigmaS-dependent gene expression in Escherichia coli. FliZ is an abundant DNA-binding protein and a global regulatory protein under the control of the flagellar master regulator FlhDC. It inhibits gene expression mediated by sigmaS by recognizing operator sequences that resemble the -10 region of sigmaS-dependent promoter. FLiZ plays a pivotal role in the decision between alternative life-styles, i.e. FlhDC-controlled flagellum-based motility or pS-dependent curli fimbriae-mediated adhesion and biofilm formation. FliZ is a global repressor with a DNA sequence specificity overlapping that of sigmaS–containing RNA polymerase, mechanism, overview 2 2.7.7.6 additional information no inhibition by 0.1 mg/ml of rifampicin, streptolydigin or alpha-amanitin 2 2.7.7.6 myxopyronin produced by the bacteria Myxococcus fulvus, inhibits initiation of RNA polymerase transcription and binding complex structure. The compounds inhibits the enzyme also from rifamycin- or multidrug-resistant bacteria. the inhibition mechanism proceeds via inhibiting DNA binding rather than affecting transcription complex stability or processivity following DNA binding, overview 39864 2.7.7.6 myxopyronin inhibits bacterial RNA polymerase and inhibits transcription on the artificially melted promoters, inhibition mechanism, overview. The antibiotic binds to a pocket deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble, binding of dMyx stabilizes refolding of the beta'-subunit switch-2 segment, resulting in a configuration that might indirectly compromise binding to, or directly clash with, the melted template DNA strand, binding structure, overview. Antibiotic binding does not prevent nucleation of the promoter DNA melting but instead blocks its propagation towards the active site. dMyx binds in the pocket deep inside the RNAP clamp head domain. Mutations designed in switch-2 mimic the dMyx effects on promoter complexes in the absence of antibiotic 39864 2.7.7.6 myxopyronin an alpha-pyrone antibiotic, targets the RNAP switch region, which is the hinge that mediates opening and closing of the RNAP active-center cleft. Lower values for inhibition by myxopyronin in the presence of template Kool NC-45 39864 2.7.7.6 myxopyronin A - 135625 2.7.7.6 Nogalamycin - 7258 2.7.7.6 Olivomycin - 94559 2.7.7.6 oxygen the enzyme is highly oxygen sensitive. Inactivation is accompanied by cross-linking of components. Inactivated enzyme can be reactivated by reduction with sodium dithionite 1180 2.7.7.6 per-O-acetyl-verbascoside compound isolated from aerial part of Buddleja cordobensis Grisebach, most active among the compounds tested 212287 2.7.7.6 procyclin-associated genes i.e. PAG1, PAG2 or PAG3, inhibit RNA synthesis, deletion of PAGs lead to increased mRNA levels, regulation of PAG expressions, overview 155593 2.7.7.6 proflavin sulfate - 114290 2.7.7.6 protein gp76 the Thermus phage protein gp76 inhibits Escherichia coli RNAP highlighting the template-DNA binding site as a target site for developing antibacterial agents 256912 2.7.7.6 protein gp76 the Thermus phage protein binds within the RNAP cleft and occupies the path of the template DNA strand at positions -11 to -4, relative to the transcription start site at +1. Thus, gp76 obstructs the formation of an open promoter complex and prevents transcription by Thermus thermophilus RNAP from most host promoters 256912 2.7.7.6 protein Rim1 the ssDNA-binding protein Rim1 severely inhibits theRNAsynthesis activity of Rpo41, but not the Rpo41-Mtf1 complex, which continues to prime DNA synthesis efficiently in the presence of Rim1 213902 2.7.7.6 protein TLS translocated in liposarcoma, a protein originally identified as the product of a chromosomal translocation, which associates with both RNAP II and the spliceosome, also represses transcription by RNAP III. It represses transcription from all three classes of RNAP III promoters in vitro and to associates with RNAP III genes in vivo. Depletion of TLS by siRNA in HeLa cells resulted in increased steady-state levels of RNAP III transcripts as well as increased RNAP III and TBP occupancy at RNAP III-transcribed genes 155598 2.7.7.6 RBL-1 oligonucleotide, efficiently inhibits 127472 2.7.7.6 RECQL5 a DNA helicase of the RECQ family, directly inhibits RNA polymerase II. It RECQL5 inhibits both initiation and elongation in transcription assays reconstituted with highly purified general transcription factors and RNAPII, RECQL5 helicase activity is not required for inhibition 155596 2.7.7.6 rifabutin - 135623 2.7.7.6 rifalazil - 135622 2.7.7.6 rifampicin 0.1 mg/ml, complete inhibition 3669 2.7.7.6 rifampicin 0.00006 mg/ml, 50% inactivation 3669 2.7.7.6 rifampicin - 3669 2.7.7.6 rifamycin - 20500 2.7.7.6 ripostatin A - 135628 2.7.7.6 SB-2 - 135630 2.7.7.6 sorangicin A - 135627 2.7.7.6 sorangicin A inhibits the wild-type and mutant (S447/S456L) RNA polymerase through different mechanisms. It has a better pharmacokinetic profile than rifampicin, making it a suitable starting molecule to design drugs to be used for the treatment of tuberculosis patients with comorbidities who require multiple medications 135627 2.7.7.6 sorangicin A inhibits the wild-type and mutant (S447/S456L) RNA polymerase through different mechanisms. It has a better pharmacokinetic profile than rifampicin, making it a suitable starting molecule to design drugs to be used for the treatment of tuberculosis patients with comorbidities who require multiple medications; the inhibitor binds in the Rif-binding pocket of RNA. It inhibits inhibits the wild-type enzyme (RNAP) by a similar mechanism as rifampicin by preventing the translocation of very short RNAs. It inhibits the RifR S456L enzyme at an earlier step, preventing the transition of a partially unwound promoter DNA intermediate to the fully opened DNA and blocking the template-strand DNA from reaching the active site in the RNAP catalytic center 135627 2.7.7.6 Spt5 the large subunit of the DRB sensitivity-inducing factor, DSIF, represses or activates RNAPII elongation in vitro. CTR1 and CTR2CT, the two repeat-containing regions constituting the C-terminus of Spt5, play a redundant role in repressing RNAPII elongation in vivo, overview. Mutant NSpt5, lacking the C-terminus, directly associates with hsp70-4 chromatin in vivo and increases the occupancy of RNAPII, positive transcription elongation factor b, histone H3 Lys 4 trimethylation, and surprisingly, the negative elongation factor A at the locus, indicating a direct action of NSpt5 on the elongation repressed locus, nuclear extracts containing the constitutively active P-TEFb and WT DSIF lead to a time-dependent increase of the long, promoter-distal RNase T1-resistant products, reflecting the elongation stimulatory activity of Spt5, overview 77930 2.7.7.6 Streptolydigin - 15970 2.7.7.6 Streptolydigin the antibiotic binds to a Tt RNAP TEC with an open trigger loop 15970 2.7.7.6 streptovaracin - 127469 2.7.7.6 streptovaricin - 114458 2.7.7.6 Tagetitoxin inhibition of RNA polymerase III 10790 2.7.7.6 Tagetitoxin no inhibition of calf thymus RNA polymerase II 10790 2.7.7.6 Tagetitoxin - 10790 2.7.7.6 Tagetitoxin 50% inhibition at 0.0001 mM. Complete inhibition at 0.01 mM 10790 2.7.7.6 terminatin factor NsiI N-terminally FLAG-tagged fusion protein Nsi1 expressed from Sf21 insect cells. Binding of the termination factor Nsi1 to its cognate DNA site is sufficient to terminate RNA polymerase I transcription in vitro and to induce termination in vivo. Nsi1 contains Myb-like DNA binding domains and associates in vivo near the 3' end of rRNA genes to rDNA. Binding of Nsi1 to a stretch of 11 nucleotides in the correct orientation is sufficient to pause elongating Pol I shortly upstream of the Nsi1 binding site and to release the transcripts in vitro, and the same minimal DNA element triggers Nsi1-dependent termination of pre-rRNA synthesis in vivo. Termination efficiency in the in vivo system can be enhanced by inclusion of specific DNA sequences downstream of the Nsi1 binding site 213904 2.7.7.6 TFAM DNA packaging by TFAM makes the DNA more resistant to unwinding 155592 2.7.7.6 ureidothiophene - 135631