RNA Polymerases Inhibitor

HNC-1664 is the orally active inhibitor for RNA-dependent RNA polymerase (RdRP). HNC-1664 exhibits broad-spectrum antiviral activity against coronavirus (SARS-CoV-2 wildtype and its mutants XBB.1.18, HK.3.1, BF.7.14, BA.1HCoV-229E, HCoV-OC43) and arenavirus. HNC-1664 exhibits anti-infectious activity in SARS-CoV-2 Delta infected mouse models.

P-536 is a ACE inhibitor that also inhibits herpes simplex virus HSV-1 thymidine kinase and Trypanosoma cruzi RNA polymerase. By inhibiting the renin-angiotensin system, downregulating the expression of AT1R and NOX4, and reducing oxidative stress (decreasing plasma hydrogen peroxide (H₂O₂) and 8-isoprostaglandin levels), P-536 effectively reduces systolic blood pressure and improves vascular reactivity. P-536 also inhibits the replication of DNA/RNA viruses such as HSV-1 by blocking nucleotide metabolism and nucleic acid synthesis, competitively inhibits RNA synthesis in Trypanosoma cruzi, and inhibits amastigote replication, thereby impeding its growth. P-536 is suitable for research on hypertension, insulin resistance, and Chagas disease.

RNAP-σ interaction-IN-4 (Compound 3a) is an inhibitor of the RNA polymerase-sigma factor interaction (RNAP-σ) with MIC values against S. pneumoniae and S. aureus of 1 μg/mL and 2 μg/mL, respectively. RNAP-σ interaction-IN-4 exhibits strong bactericidal properties by interfering with the interaction of β′CH−σ and disrupting the transcription of bacteria. RNAP-IN-2 shows significant efficacy in sepsis models. RNAP-σ interaction-IN-4 can be used to study Gram-positive bacterial infections caused by multi-drug resistant strains.

Rifaquizinone (CBR-2092; TNP-2092) is a rifamycin-quinolone hybrid antibiotic. Rifaquizinone has an IC₅₀ of 0.034 μM against wild-type Staphylococcus aureus DNA-dependent RNA polymerase. Rifaquizinone potently inhibits Staphylococcus aureus infection, with an MIC range of 0.008-0.5 μg/mL against 300 clinical isolates of staphylococci and streptococci. Rifaquizinone can be used in research related to persistent Staphylococcus aureus infections.

Favipiravir-¹³C¹⁵N (T-705-¹³C¹⁵N) is ¹³C and ¹⁵N labeled Favipiravir. 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.

Pol I-IN-1 is a potent RNA polymerase I (Pol I) inhibitor with IC₅₀ 0.21 µM for the Pol I large catalytic subunit RPA194.

TR-213 is a potent molecular glue degrader that targets Cyclin K (CDK). TR-213 induces 91% and 56% decrease in CDK12 and Cyclin at 1 μM. TR-213 can inhibit RNA polymerase II activity and regulates alternative polyadenylation (APA) activity. TR-213 can be used for the research of cancer.

ALS-8112-TP is the 5'-triphosphate metabolite of ALS-8112 (HY-12983). ALS-8112-TP is a potent, selective and competitive respiratory syncytial virus (RSV) RNA polymerase inhibitor, with selectivity against polymerases from host or viruses unrelated to RSV such as hepatitis C virus (HCV). ALS-8112-TP can be efficiently recognized by the recombinant RSV polymerase complex, causing chain termination of RNA synthesis. ALS-8112-TP can be used for RSV-infection research.

4-Demethoxy-7,9-di-epi-daunorubicin, a derivative of Daunorubicin (HY-13062A), is an anthracycline antibiotics. 4-Demethoxy-7,9-di-epi-daunorubicin can bind to calf thymus DNA and forms a complex with the stacked DNA base pairs. 4-Demethoxy-7,9-di-epi-daunorubicin can inhibit prokaryotic nucleic acid polymerases, including E. coli DNA polymerase I and RNA polymerase. 4-Demethoxy-7,9-di-epi-daunorubicin can be used for researches of cancer and infection.

CDK-IN-9 (compound 24) is a potent CDK inhibitor, also as a molecular glue inducing an interaction between CDK12 and DDB1, with an IC₅₀ values of 4 nM for CDK2/E. CDK-IN-9 leads to polyubiquitination of cyclin K and its subsequent degradation. CDK-IN-9 induce apoptosis through dephosphorylation of retinoblastoma protein and RNA polymerase II.

Adafosbuvir (AL-335), a precursor compound of a uridine-based nucleotide analog polymerase (NS5B) inhibitor, has potent antiviral activity against HCV and acts as a potent inhibitor of HCV RNA polymerase.

Tirandamycin A, an antibiotic, is a bacterial RNA polymerase inhibitor. Tirandamycin A has antiamoebic and antibacterial properties.

Antiviral agent 81 is an orally bioavailable N-acylated remdesivir derivative and RdRp inhibitor with 45.3% oral bioavailability (based on active metabolite GS-441524 exposure), plasma half-life >8 h, and reduced CYP3A4 inhibition. Antiviral agent 81 exhibits activity against Coronaviridae, Flaviviridae, and Pneumoviridae, and shows no activity against Orthomyxoviridae, Herpesviridae, and Alphaviridae. Antiviral agent 81 can be used for the research of viral infections.

RdRP-IN-6 (compound 27) inhibits RNA dependent-RNA polymerase (RdRp) with an IC₉₀ value of 14.1 μM. RdRP-IN-6 can be used for research on antiviral and anticancer.

CX-5461 hydrochloride is a selective, orally active RNA polymerase I inhibitor. CX-5461 hydrochloride disrupts the formation of the SL1-rDNA complex, thereby blocking the transcription initiation of ribosomal RNA without altering the activity of RNA polymerase II, DNA replication, or protein translation processes. CX-5461 hydrochloride upregulates the expression of p21, MDM2, Sestrin1/2, and phosphorylated AMPKα, and reduces the level of phosphorylated Akt. CX-5461 hydrochloride induces G2/G2/M cell cycle arrest, Autophagy, Apoptosis, and cellular senescence, and activates CHK1, CHK2, and RPA. CX-5461 hydrochloride can be used in research related to osteosarcoma, cervical cancer, hematologic malignancies, high-grade serous ovarian cancer, and solid tumors.

Dihydromyricetin-d₄ (Ampelopsin-d₄) is deuterium labeled Dihydromyricetin. 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.

RNA polymerase-IN-3 (Compound 28) is a bacterial RNA polymerase (RNAP) inhibitor with antibacterial activity. RNA polymerase-IN-3 inhibits RNA synthesis by competitively blocking the binding of UTP to RNAP (IC₅₀= 0.28 μM). RNA polymerase-IN-3 is promising for research of bacterial infections.

LMed 93 is an antiviral agent. LMed 93 inhibits the activity of influenza A virus RNA polymerase. LMed 93 suppresses viral RNA synthesis. LMed 93 inhibits the replication of influenza A viruses H5N1 and H1N1. LMed 93 can be used for the research of influenza A virus infections (H1N1, H5N1).

Pipobroman (Standard) is the analytical standard of Pipobroman. This product is intended for research and analytical applications. Pipobroman is a bromide derivative of piperazine and acts as an alkylating agent. Pipobroman plays its role by inhibiting DNA and RNA polymerase or by reducing pyrimidine nucleotide incorporation into DNA. Pipobroman can be used for the cancer research, including polycythemia vera, myeloproliferative neoplasm, and AML et.al.

CGP 4832 is a Rifamycin S (HY-125365) derivative and Antibacterial agent. CGP 4832 inhibits DNA-dependent transcription through DNA-dependent RNA polymerase. CGP 4832 exhibits activity against Gram-positive bacteria comparable to Rifampicin (HY-B0272), but is more potent against certain Gram-negative bacterial species, such as Escherichia coli ETH 2018 (MIC 0.01 µg/mL) and Salmonella AX 5 (MIC 0.5 µg/mL). CGP 4832 can be used for research on Gram-negative bacterial infections.