polymerases

BCH001 is a specific small-molecule inhibitor of PAPD5.

Pimodivir (VX-787), an influenza A virus polymerases inhibitor via oral, interacts with the viral PB2 subunit.

GS-441524 was shown to be a safe and effective treatment for feline infectious peritonitis (FIP). The optimum dosage was found to be 4.0 mg/kg SC q24h for at least 12 weeks

GS-443902 trisodium (GS-441524 triphosphate trisodium), the active triphosphate metabolite of Remdesivir (GS-5734), serves as a potent inhibitor of viral RNA-dependent RNA-polymerases (RdRp), displaying inhibitory concentrations (IC50) of 1.1 μM for RSV RdRp and 5 μM for HCV RdRp.

Acyclovir sodium is a guanosine nucleoside analogue and viral DNA polymerase inhibitor with antiviral activity, used to treat skin and mucous membrane HSV infections, exhibiting significant activity against HSV-1, HSV-2, and VZV.

Juglone (Regianin) is a natural naphthoquinone found in the black walnut (J. nigra) and other plants in the Juglandaceae family. Juglone also irreversibly inhibits peptidyl-prolyl cis/trans isomerases of the parvulin family, including human Pin1, yeast Ess1/Ptf1, and E. coli parvulin (Ki = 55.9 nM). Juglone also blocks transcription by RNA polymerases I, II, and III (IC50s = 2-7 μM) and attenuates kidney fibrosis in rats treated with unilateral ureteral obstruction, both through Pin1-independent mechanisms.

Tubercidin (Sparsomycin A), an adenosine analogue, is a nucleoside antibiotic. It is incorporated into DNA and inhibits polymerases, thereby inhibiting DNA replication and RNA and protein synthesis. This agent also exhibits antifungal and antiviral activities.

Tenofovir diphosphate TEA (TFV-DP TEA) is the triethylamine salt of TFV-DP, an ATP-competitive DNA polymerase inhibitor that inhibits HIV-1 reverse transcriptase. It has anti-HIV/HBV potential through its incorporation into the viral DNA strand to terminate viral DNA synthesis and thus inhibit viral genome replication.

1, 5-Isoquinolinediol is an inhibitor of poly(ADP-ribose) synthetase (PARP1; IC50: 0.39 μM). The poly(ADP-ribose) polymerases (PARPs) form a family of enzymes with roles in DNA repair and apoptosis. 1, 5-Isoquinolinediol has been used to study the role of

PSI-7409 tetrasodium is the pharmacologically active 5′-triphosphate metabolite of sofosbuvir (PSI-7977) that directly inhibits hepatitis C virus NS5B RNA-dependent RNA polymerase, with IC50 values of 1.6, 2.8, 0.7, and 2.6 μM against GT 1b_Con1, GT 2a_JFH1, GT 3a, and GT 4a NS5B polymerases, respectively, PSI-7409 tetrasodium is widely used to study antiviral mechanisms and genotype-specific polymerase inhibition.

Streptolydigin inhibits RNA synthesis by binding to RNA polymerase and does not inhibit eukaryotic RNA polymerases. Streptolydigin is a 3-acetyltetramic acid antibiotic and a potent bacterial RNA polymerase inhibitor (Ki: 18 μM and a Kd: 15 μM).

Lucidenic lactone is a terpene compound that acts as an inhibitor of DNA polymerases. It inhibits calf DNA polymerase-α, rat DNA polymerase-β, and HIV-1 reverse transcriptase with IC50 values of 42 μM, 99 μM, and 69 μM, respectively.

Lucidenic acid O is a terpene compound that acts as an inhibitor of DNA polymerases. Lucidenic lactone inhibits calf DNA polymerase-α, rat DNA polymerase-β, and HIV-1 reverse transcriptase, with IC50 values of 42 μM, 99 μM, and 69 μM, respectively.

PARP1-IN-37 (Compound 8) is an orally active and selective inhibitor of poly (ADP-ribose) polymerases 1 and 2 (PARP1/2), with an IC50 value of 24 nM for PARP1. It inhibits PARP activity in cells with an EC50 value of 3.7 μM and holds potential for research on BRCA-mutated tumors, such as breast and ovarian cancers.

3′-Deoxy CTP is a nucleotide analog that functions as a potent chain terminator. By lacking a 3′-hydroxyl group, 3′-Deoxy CTP induces chain termination, thereby inhibiting the RNA synthesis activity of HCV non-structural protein (NS5B) polymerase and halting viral replication. This compound is useful for studying the chain termination mechanism of HCV polymerases and for developing antiviral drugs.

PMEG-DP disodium is an effective inhibitor of DNA polymerase (IC50=2.5 μM), exerting strong inhibitory effects particularly on DNA polymerases α and δ. As the active metabolite of GS-9191, it efficiently impedes the growth of cell lines infected with human papillomavirus (HPV). PMEG-DP disodium is useful in research related to HPV-associated diseases.

PNU-183792 is a 4-oxo-1,4-dihydroquinoline that acts as an orally active inhibitor of herpesvirus polymerases (HSV polymerases). It exhibits broad-spectrum antiviral activity, with IC50 values of 0.69 μM for human cytomegalovirus (HCM), 0.37 μM for varicella-zoster virus, and 0.58 μM for herpes simplex virus (HSV) polymerase. PNU-183792 shows no activity against human α, γ, and δ polymerases but inhibits simian varicella virus (SVV), murine cytomegalovirus (MCMV), and rat cytomegalovirus (RCMV).

Polθ-IN-9 is an orally active inhibitor of Polθ polymerase with an IC50 of 9.6 nM and a Kd of 47.5 nM. It demonstrates remarkable selectivity, showing no inhibitory activity against other human DNA polymerases, such as Pol α, Pol ε, Pol γ, Pol λ, and Pol μ. In DLD1 BRCA2 KO cells, Polθ-IN-9 exhibits potent antiproliferative activity with an IC50 of 2.9 μM, and it is highly sensitive to MDA-MB-436 cells with an IC50 of 4.9 μM. In MDA-MB-436 xenograft tumor models, the combination of Polθ-IN-9 with Olaparib enhances DNA damage accumulation, increases γH2AX levels, and inhibits tumor growth. Polθ-IN-9 is useful in studying homologous recombination (HR)-deficient cancers such as breast cancer.

4-Demethoxy-7,9-di-epi-daunorubicin is a derivative of Daunorubicin and an anthracycline antibiotic (antibiotics). It binds to calf thymus DNA, forming a complex with stacked DNA base pairs. This compound inhibits nucleic acid polymerases in prokaryotes, including Escherichia coli DNA polymerase I (DNA polymerase I) and RNA polymerase (RNA polymerase). 4-Demethoxy-7,9-di-epi-daunorubicin is utilized in cancer and infection research.

GHP-88310 (EIDD-3608) is a potent, orally active inhibitor of orthoparamyxovirus polymerases. It exhibits strong activity against Human Parainfluenza Virus Type 3 (HPIV3) and related respiratory viruses, as well as Measles Virus (MeV) and associated measles pathogens. GHP-88310 has demonstrated effectiveness in both the canine distemper virus (CDV) ferret model and the HPIV3 cotton rat model. This compound is useful for researching orthoparamyxovirus-related diseases.

ALS-8112-TP is the 5'-triphosphate metabolite of ALS-8112. This compound acts as a potent, selective, and competitive inhibitor of respiratory syncytial virus (RSV) RNA polymerase, demonstrating selectivity over host or unrelated viral polymerases, such as the hepatitis C virus (HCV). It is efficiently recognized by the recombinant RSV polymerase complex, resulting in the termination of RNA synthesis. ALS-8112-TP is applicable in the research of RSV infections.

Etidaligide is a DNA repair inhibitor designed to prevent the repair of DNA damage in tumor cells. It also activates DNA-dependent protein kinases (DNA-PK) and poly (ADP-ribose) polymerases, enzymes that promote the phosphorylation of H2AX and the parylation of proteins.

4'-Azidothymidine 5'-triphosphate exerts selectively action on both reverse transcriptase of human immunodeficiency virus type 1 and human DNA polymerases alpha and beta.

3'-Deoxyuridine-5'-triphosphate (3'-dUTP) is a nucleotide analogue that inhibits DNA-dependent RNA polymerases I and II and strongly competes with UTP incorporation into RNA, with a Ki value of 2.0 μM[1].