RNA Polymerases Inhibitor

CX-5461 is a potent and oral rRNA synthesis inhibitor. It inhibits RNA polymerase I-driven transcription of rRNA with IC₅₀s of 142, 113, and 54 nM in HCT-116, A375, and MIA PaCa-2 cells, respectively.

Favipiravir (T-705) is a potent viral RNA polymerase inhibitor, it is phosphoribosylated by cellular enzymes to its active form, Favipiravir-ribofuranosyl-5′-triphosphate (RTP). Favipiravir-RTP inhibits the influenza viral RNA-dependent RNA polymerase (RdRP) activity with an IC₅₀ of 341 nM.

IMT1 is a first-in-class specific and noncompetitive human mitochondrial RNA polymerase (POLRMT) inhibitor. IMT1 causes a conformational change of POLRMT, which blocks substrate binding and transcription in a dose-dependent way in vitro. IMT1 reduces deoxynucleoside triphosphate levels and citric acid cycle intermediates, resulting in a marked depletion of cellular amino acid levels. IMT1 has the potential for mitochondrial transcription disorders related diseases.

Dihydromyricetin is a potent inhibitor with an IC₅₀ of 48 μM on dihydropyrimidinase. Dihydromyricetin can activate autophagy through inhibiting mTOR signaling. Dihydromyricetin suppresses the formation of mTOR complexes (mTORC1/2). Dihydromyricetin is also a potent influenza RNA-dependent RNA polymerase inhibitor with an IC₅₀ of 22 μM.

BMH-21 is a first-in-class DNA intercalator which inhibits RNA polymerase I (Pol I) transcription. BMH-21 possesses anticancer activity.

7-Aminoactinomycin D (solution) (7-AAD (solution)) a cell-impermeant fluorescent DNA stain, is a potent RNA polymerase inhibitor. 7-Aminoactinomycin D selectively binds to GC regions of the DNA. 7-Aminoactinomycin D also has antibacterial effects.
Solvent and concentration: DMSO: 1 mg/mL

IMT1B (LDC203974) is an orally active, noncompetitive and specific allosteric inhibitor of mitochondrial RNA polymerase (POLRMT) and inhibits mitochondrial DNA (mtDNA) expression. IMT1B has anti-tumour effects.

Simeprevir (TMC435; TMC435350) is an oral, potent and highly specific hepatitis C virus (HCV) NS3/4A protease inhibitor with a K_i of 0.36 nM. Simeprevir inhibits HCV replication with an EC₅₀ of 7.8 nM. Simeprevir also potently suppresses SARS-CoV-2 replication and synergizes with Remdesivir. Simeprevir inhibits the main protease (M^pro) and the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, and also modulates host immune responses.

Cynaroside (Luteolin 7-glucoside) is a flavonoid compound that exhibits anti-oxidative capabilities. Cynaroside is also a potent influenza RNA-dependent RNA polymerase inhibitor with an IC₅₀ of 32 nM. Cynaroside also is a promising inhibitor for H₂O₂-induced apoptosis, has cytoprotection against oxidative stress-induced cardiovascular diseases. Cynaroside also has antibacterial, antifungal and anticancer activities, antioxidant and anti-inflammatory activities.

Enitociclib ((+)-BAY-1251152; (+)-VIP152) is a selective CDK9 inhibitor (IC₅₀=3 nM) that inhibits transcriptional elongation by blocking Ser2/Ser5 phosphorylation of RNA polymerase II. Enitociclib specifically depletes key short-lived proteins such as c-MYC, MCL-1 and induces tumor cell apoptosis. Enitociclib also interferes with the production of enhancer RNAs (eRNA) and enhancer-promoter interactions, and downregulates oncogene expression at the epigenetic level. Enitociclib exerts synergistic effects with agents including Bortezomib (HY-10227), Lenalidomide (HY-A0003), Pomalidomide (HY-10984), Venetoclax (HY-15531) and Paclitaxel (HY-B0015), and even reverses paclitaxel resistance. Enitociclib serves as a vital research tool for various malignancies such as double-hit diffuse large B-cell lymphoma, multiple myeloma and pancreatic ductal adenocarcinoma.

7-Aminoactinomycin D (7-AAD) a cell-impermeant fluorescent DNA stain, is a potent RNA polymerase inhibitor. 7-Aminoactinomycin D selectively binds to GC regions of the DNA. 7-Aminoactinomycin D also has antibacterial effects.

Fidaxomicin (OPT-80), a macrocyclic antibiotic, is an orally active and potent RNA polymerase inhibitor. Fidaxomicin has a narrow spectrum of antibacterial activity and a good anti-Clostridium difficile activity (MIC₉₀=0.12 μg/mL). Fidaxomicin can be used for Clostridium difficile infection (CDI) research.

Rifaximin, a gastrointestinal-selective antibiotic, binds the β-subunit of bacterial DNA-dependent RNA polymerase, resulting in inhibition of bacterial RNA synthesis. Rifaximin susceptibility is higher against Gram-positive strains (MIC: 0.03-5 mg/ml) compared to Gram-negative bacteria (MIC: 8-50 mg/mL).

Dirhodium tetraacetate (Tetrakis (acetato) dirhodium (II)) is an anticancer agent. Dirhodium tetraacetate functionally inhibits the activities of DNA polymerase I and RNA polymerase. It also acts as a catalyst and can be used to construct rhodium-based artificial metalloenzymes.

Galidesivir (BCX4430), an adenosine analog and a direct-acting antiviral agent, disrupts viral RNA-dependent RNA polymerase (RdRp) activity. Galidesivir is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV, SARS-CoV, and SARS-CoV-2. Galidesivir inhibits some negative-sense RNA viruses with EC₅₀s ranging from ~3 to ~68 μM.

Dasabuvir (ABT-333) is a nonnucleoside hepatitis C virus (HCV) polymerase inhibitor. Dasabuvir inhibits RNA-dependent RNA polymerase encoded by the HCV NS5B gene. Dasabuvir inhibits genotype 1a (strain H77) and 1b (strain Con1) replicons, with EC₅₀ values of 7.7 and 1.8 nM, respectively.

2'-O-Methylcytidine is an orally active 2'-substituted nucleoside as a inhibitor of HCV replication with antiviral activity. 2'-O-Methylcytidine inhibits RNA-dependent RNA polymerase (NS5B)-catalyzed RNA synthesis in vitro, in a manner that is competitive with substrate nucleoside triphosphate.

Thiolutin (Acetopyrrothin) is a sulfur-containing antibiotic, which is a potent inhibitor of bacterial and yeast RNA polymerases. Thiolutin can be produced by Streptomyces. Thiolutin inhibits AMSH (IC₅₀ = 4 μM) and Rpn11 (IC₅₀ = 0.53 μM). Thiolutin is a dual inhibitor of BRCC36 and the NLRP3 inflammasome, exhibiting anti-inflammatory effects. Thiolutin effectively suppresses the interaction between BRCC36 and HMGCR, leading to the inhibition of HCC growth. Thiolutin attenuates pyroptosis and NLRP3 inflammasome activation. Thiolutin markedly alleviates renal injury and inflammatory process in IgAN. Thiolutin is an anti-angiogenic compound which can ease Doxorubicin-induced cardiotoxicity (DOXIC)^{[1][2][3][4][5]}.

Onradivir (ZSP1273) is an orally active antiviral agent targeting influenza A virus RNA polymerase PB2 subunit with an IC₅₀ of 0.562 nM. Onradivir inhibits cap binding to influenza A virus RNA polymerase PB2 subunit, suppresses viral replication, reduces viral titres and RNA loads, and inhibits influenza A virus infection. Onradivir maintains high survival rates in influenza A virus-infected mice, and reduces influenza A virus titers in a murine model. Onradivir can be used for the research of influenza A virus infection.

β-Amanitin is a cyclic peptide toxin in the poisonous Amanita phalloides mushroom. β-Amanitin inhibits inhibits eukaryotic RNA polymerase II and III. β-Amanitin inhibits protein synthesis. β-Amanitin can be used as a cytotoxic component of antibody-drug conjugates (ADCs).