rna polymerase

RNA polymerase II-IN-2 (compound 20iii), a potent inhibitor of RNA polymerase II (Pol II) with a K i value of 9.5 nM, exhibits cytotoxicity against cancer cells, demonstrating toxicity levels 2 and 5 times higher than α-amanitin in CHO and HEK293 cells, respectively [1].

T7 RNA polymerase, expressed by Escherichia coli from the T7 bacteriophage RNA polymerase gene, is a highly specific enzyme utilized for in vitro transcription (IVT) of mRNA. This polymerase requires Mg 2+ and selects only DNA templates that contain the T7 promoter sequence, whether single-stranded or double-stranded. It employs NTPs to synthesize RNA that is complementary to the single-stranded DNA following the promoter [1] [2].

RNA polymerase-IN-2 (compound 5) acts as an inhibitor of DNA-dependent RNA polymerase. Additionally, it inhibits CYP isozymes [1].

RNA polymerase II-IN-1 (compound 19iv), an amatoxin, selectively inhibits RNA polymerase II (Pol II) with an IC50 of 36.66 nM and exhibits heightened cytotoxicity towards cancer cells while reducing toxicity in normal cells compared to α-Amanitin [1].

RNA polymerase-IN-1 (compound 4) acts as an inhibitor of DNA-dependent RNA polymerase. Additionally, it inhibits CYP isozymes [1].

Remdesivir (GS-5734) is a nucleoside analog, a broad-spectrum antiviral compound that exerts its activity by inhibiting the RNA-dependent RNA polymerase of viruses. Remdesivir is active against Ebola, SARS, and MERS viruses, and is potentially therapeutic against COVID-19.

Favipiravir is a potent and selective RNA-dependent RNA polymerase inhibitor for the treatment of influenza virus infections.

AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC). It interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis. AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II, and acts synergistically with DNA damaging agents to inhibit tumor cell growth.

Uprifosbuvir (MK-3682) is a uridine nucleoside monophosphate prodrug inhibitor of hepatitis C virus NS5B RNA polymerase with antiviral activity for the study of chronic hepatitis C virus.

JTK-109 is an inhibitor of hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitor and inhibits G1b and G3a subgenomic replicons and recombinant enzymes.

Filibuvir (PF-00868554) is a selective and noncovalent inhibitor of HCV NS5B RNA-dependent RNA polymerase. Filibuvir inhibits genotype 1a and 1b replicons with EC50s of 59 nM.

AS-136A is an orally active measles virus RNA-dependent RNA polymerase (RdRp) inhibitor with antiviral activity that inhibits measles virus and blocks viral RNA synthesis.

Setrobuvir (ANA-598) is an orally active non-nucleoside HCV NS5B polymerase inhibitor with inhibitory effects on de novo RNA synthesis and primer extension with IC50s between 4 and 5 nM. setrobuvir shows good binding affinity for SARS-CoV-2 RdRp and induces inhibition of RdRp.

A09-003 is a novel cell cycle protein-dependent kinase-9 CDK-9 inhibitor.A09-003 inhibits the proliferation of a variety of leukemia cell lines and inhibits the increase of leukemia sequence-1 protein in myeloid cells.A09-003 also induces apoptosis, decreases RNA polymerase II activity, and decreases Mcl-1 expression.

Foscarnet sodium (Phosphonoformate) is an antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV.

N-Dodecyl-β-D-maltoside (Lauryl Maltoside) is an alkyl maltopyranoside detergent, particularly useful in transporters and respiratory complexes. It is a derivative of pyrene (Py) and has applications in the purification and stabilization of RNA polymerase, as well as the detection of protein-lipid interactions.

Rifaximin is an orally administered, semi-synthetic, nonsystemic antibiotic derived from rifamycin SV with antibacterial activity. Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis and bacter

Rifabutin (LM-427) inhibits bacterial DNA-dependent RNA polymerase, thereby suppressing the initiation of RNA formation and leading to inhibition of RNA synthesis and transcription. Rifabutin is a semisynthetic ansamycin antibiotic with potent antimycobacterial properties.

Rifamycin S is a potent DNA-dependent RNA polymerase inhibitor,is a quinone and an antibiotic agnet against Gram-positive bacteria

Fidaxomicin (Tiacumicin B) is a semisynthetic macrolide antibiotic used to treat Clostridium difficile-associated diarrhea in adults. Fidaxomicin has minimal systemic absorption and has not been linked to serum enzyme elevations during therapy or to instances of clinically apparent, acute liver injury.

Methyl 2-amino-5-bromobenzoate (Methyl 5-Bromoanthranilate) is a hepatitis C virus NS5b RNA polymerase inhibitor with antimicrobial activity that inhibits Pseudomonas aeruginosa infections and is involved in the production of many virulence factors and biofilm formation.

Rifamycin sodium (Rifamycin sodium salt) salt is an antibiotic that inhibits bacterial DNA-dependent RNA polymerase. It is effective against Gram-positive bacteria.

Baloxavir (S-033447) is a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit.

Floxuridine (FUDR) is an antimetabolite, floxuridine inhibits thymidylate synthase, resulting in disruption of DNA synthesis and cytotoxicity.

2’-beta-C-Methyl inosine (2’-C-Methylinosine) is an HCV RNA polymerase inhibitor with antiviral activity and is being studied for the treatment of hepatitis C virus infection.

(S)-Enitociclib (VIP152) is a selective CDK9 inhibitor that induces complete regression of MYC+ lymphomas by inhibiting RNA polymerase II-mediated transcription of anti-apoptotic and pro-survival proteins.

Talviraline (Bay 10-8979) is an RNA-induced DNA polymerase inhibitor.Talviraline is a potent inhibitor of HIV-1-induced cell killing and HIV-1 replication in a variety of human cell lines, as well as in fresh human peripheral blood lymphocytes and macrophages.

Galidesivir hydrochloride is an inhibitor of viral RNA-dependent RNA polymerase (RdRp). It inhibits SARS-CoV-2 by tightly binding to its RdRp.

Galidesivir is a viral RNA-dependent RNA polymerase (RdRP) inhibitor and broad spectrum antiviral nucleotide.In vitro, galidesivir displays antiviral activity against a range of RNA viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses, and flaviviruses (EC50values range from 3 μM to >100 μM). Galidesivir protects against Ebola and Marburg viral infection in animal models.

TMC-649128 PM is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC(50) value of 1.2 muM and showing moderate in vivo bioavailability in rat (F=14%).

IMT1B (LDC203974) is an orally administered, specific noncompetitive allosteric inhibitor of mitochondrial RNA polymerase (POLRMT), effectively suppressing mitochondrial DNA (mtDNA) expression and conferring anti-tumor properties.

Galidesivir (BCX4430) is a broad-spectrum antiviral compound, an adenosine analog that inhibits viral RNA-dependent RNA polymerase (RdRp) activity.Galidesivir inhibits a wide range of RNA viral pathogens in vitro, and reduces lung infections in infected animals.

BMH-21, a small molecule DNA intercalator, binds ribosomal DNA and inhibits RNA polymerase I (Pol I) transcription and not affects phosphorylation of H2AX.

Sotetsuflavone, with an IC50 of 0.16 μM, stands as the most active compound in its series, acting as a potent inhibitor of DENV-NS5 RdRp (Dengue virus NS5 RNA-dependent RNA polymerase).

Cynaroside (Luteolin 7-O-Glucoside) is a flavone, a flavonoid-like chemical compound. It has an anti-oxidant effect, inhibiting lipid and protein oxidation.

Dasabuvir (ABT-333) is a non-nucleoside inhibitor of the hepatitis C virus (HCV) non-structural protein 5B (NS5B), an RNA-dependent RNA polymerase. Upon administration and intracellular uptake, dasabuvir binds HCV NS5B polymerase, blocking viral RNA synthesis and replication. The HCV NS5B protein is essential for the replication of the HCV RNA genome.

Simeprevir (TMC435) is a potent HCV NS3 4A protease inhibitor, and inhibits HCV replication with EC50 of 8 nM.

Mericitabine (R-7128) is a nucleoside HCV NS5B polymerase inhibitor. It acts as an RNA chain terminator and prevents the elongation of RNA transcripts during replication.

NITD-2 is a dengue virus (DENV) polymerase inhibitor, inhibits the DENV RdRp-mediated RNA elongation. NITD-2 penetrates cell membrane poorly. Dengue virus (DENV) is the most prevalent mosquito- borne viral pathogen in humans. Neither vaccine nor antiviral therapy is currently available for DENV.

FIT-039 is a selective and ATP-competitive, orally active inhibitor of CDK9( IC50 : 5.8 μM;CDK9 cyclin T1). FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses.

3,4-Dihydroxybenzylamine hydrobromide (NSC-263475 hydrobromide) inhibits DNA polymerase activity in melanoma cells and displays growth inhibitory activity in melanoma cell lines with varying degrees of tyrosinase activity.

Emivirine (MKC-442) is a potent and selective nonnucleoside reverse transcriptase inhibitor for human immunodeficiency virus type 1.

Clevudine (Levovir) is a synthetic pyrimidine analogue with activity against hepatitis B virus (HBV). Intracellularly, clevudine is phosphorylated to its active metabolites, clevudine monophosphate and triphosphate. The triphosphate metabolite competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). Clevudine has a long half-life and shows significant reduction of covalently closed circular DNA (cccDNA), therefore the patient is less likely to have a relapse after treatment is discontinued.

PSI-6206 (RO 2433) (RO2433) is a selective HCV RNA polymerase inhibitor.

ZYN57939 (MTR-106) is RNA polymerase I inhibitor for treating RNA polymerase I- mediated diseases. ZYN57939 showed inhibitory activity with IC50 of 0.855 μM against human HT- 29 cancer cell lines.

RdRP-IN-2 is an RNA-dependent RNA polymerase (RdRp) inhibitor that significantly inhibits SARS-CoV-2 RdRp with an IC50 of 41.2 µM and also inhibits Feline coronavirus (FIPV) replication.

Metarrestin (ML246) is a first-in-class perinucleolar compartment inhibitor with a favorable PK profile, which effectively suppresses metastasis. Metarrestin disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, at least in part by interacting with the translation elongation factor eEF1A2.

POL1-IN-1 (Compound 3A) can effectively inhibit the transcription of RNA polymerase I in the A375 malignant melanoma cell line but has no effect on polymerase II.