DNA Polymerases Inhibitor

Apricitabine (SPD754; AVX754), the (-) enantiomer of 2′-deoxy-3′-oxa-4′-thiocytidine (dOTC), is a highly selective and orally active HIV-1 reverse transcriptase (RT) inhibitor (K_i=0.08 μM), as well as inhibits DNA polymerases α, β, and γ with K_i value of 300 μM, 12 μM, and 112.25 μM, respectively. Apricitabine (SPD754; AVX754) shows promising antiretroviral efficacy, good tolerability and a low propensity for resistance selection in antiretroviral-naive HIV infection.

Fiacitabine (NSC 382097; FIAC; FOAC) is a potent and highly selective anti-herpesvirus agent. Fiacitabine acts as an inhibitor of HSV DNA polymerase, with a K_i of 0.26 μM for HSV-1 and 0.42 μM for HSV-2, respectively. Fiacitabine can be efficiently phosphorylated by thymidine kinase encoded by the virus itself to generate FIACTP, an active triphosphate metabolite. Fiacitabine is applicable to research related to herpesvirus infections.

Ganciclovir triphosphate (GCV-TP) is a competitive DNA polymerase inhibitor and a metabolite of Ganciclovir (HY-13637). Ganciclovir triphosphate can replace Guanine-5'-triphosphate to terminate DNA chain extension, and mimics dGTP (HY-138616) to compete with mammalian DNA polymerases. Ganciclovir triphosphate can be used in research related to HSV infection, retinoblastoma, glioblastoma and colorectal cancer.

Cytarabine-d₂ is the deuterium labeled Cytarabine. Cytarabine, a nucleoside analog, causes S phase cell cycle arrest and inhibits DNA polymerase. Cytarabine inhibits DNA synthesis with an IC₅₀ of 16 nM. Cytarabine has antiviral effects against HSV.

Roseoside is an inhibitor of DNA gyrase and HAV 3C protease, and also inhibits HCV NS5A/B replicase in human systems with an IC₅₀ of 20 μM. Roseoside binds to the active site of enzymes and stabilizes the interaction by forming hydrogen bonds with key amino acid residues. Roseoside inhibits the growth of Gram-positive bacteria, Gram-negative bacteria, and Candida albicans, and interferes with HCV RNA replication in vitro by inhibiting HCV NS5A/B replicase (IC₅₀=20 μM). Roseoside shows no cytotoxicity and serves as a research tool for studies related to bacterial infections, candidiasis, HAV and HCV.

DNA polymerase-IN-6 is an antiviral agent and a DNA polymerase inhibitor. DNA polymerase-IN-6 inhibits the replication of HCMV, HSV-1, HSV-2 and EBV. DNA polymerase-IN-6 exhibits low cytotoxicity in mammalian cells. DNA polymerase-IN-6 can be used in research related to viral infections.

3'-Fluorothymidine-5'-triphosphate tetrasodium (3'-FdTTP tetrasodium) is a dTTP (HY-138615) analog. 3'-Fluorothymidine-5'-triphosphate tetrasodium inhibits the T4 DNA polymerases competitively with dTTP. 3'-Fluorothymidine-5'-triphosphate tetrasodium inhibits DNA synthesis by T4 wild-type, L98 and CB121 DNA polymerase.

Fludarabine triphosphate (F-ara-ATP), the active metabolite of Fludarabine (HY-B0069), is a potent, noncompetitive and specific inhibitor of DNA primase, with an IC₅₀ of 2.3 μM and a K_i of 6.1 μM. Fludarabine triphosphate inhibits DNA synthesis by blocking DNA primase and primer RNA formation. Fludarabine triphosphate inhibits ribonucleotide reductase and DNA polymerase and ultimately leads to cellular apoptosis.

FF-10502, a structural analog of Gemcitabine, is a pyrimidine nucleoside antimetabolite. FF-10502 inhibits DNA polymerase α and β. FF-10502 shows beneficial anticancer activity via a mechanism of action on dormant cells.

ART6043 (Polθ-IN-7) is an orally active, selective allosteric DNA polymerase θ (Polθ) inhibitor with an IC₅₀ of 1.3 nM. ART6043 blocks microhomology-mediated end joining (MMEJ) by inhibiting the polymerase function of Polθ. ART6043 suppresses the survival of homologous recombination-deficient (HRD) cells and enhances the antitumor effects of PARP inhibitors. ART6043 can be used in studies of HRD tumors, including BRCA1-mutant triple-negative breast cancer, BRCA2-deficient colorectal cancer, RAD51C-deficient gastric cancer, and others.

RTx-303 is an orally active, selective DNA polymerase θ (Polθ) inhibitor (IC₅₀ = 5.1 nM). RTx-303 exhibits significantly high cellular potency and strongly potentiates PARPi in BRCA1/2 mutant cells and patient-derived xenograft models. RTx-303 can be used for the study of BRCA2-mutated breast cancer.

Cidofovir (GS 0504; HPMPC; (S)-HPMPC) dihydrate is an acyclic monophosphate nucleotide analogue and CMV inhibitor with antiviral activity. Cidofovir dihydrate inhibits cytomegalovirus (CMV) replication by selectively inhibiting viral DNA polymerase. Cidofovir dihydrate induces apoptosis and can be used in studies of AIDS cytomegalovirus retinitis, herpes, and cancer. Cidofovir dihydrate also has anti-orthopoxvirus and anti-variola activities.

AZD4956 is a potent and selective DNA polymerase theta (POLQ) inhibitor. AZD4956 exhibits an IC₅₀ value of less than 3 μmol/L against POLQ and 3.4 μmol/L against MMEJ. AZD4956 suppresses the MMEJ pathway and enhances the activity of DNA-damaging agents in HRR-deficient cellular contexts. AZD4956 shows antitumor activity in BRCA1/2-mutated triple-negative breast cancer and prostate cancer models. AZD4956 can be used for the study of homologous recombination-deficient tumors.

(+)-Plakevulin A (Plakevulin A) is an oxylipin and can be isolated from an Okinawan sponge Plakortis sp. (+)-Plakevulin A inhibits the enzymatic activity of DNA polymerases α and δ. (+)-Plakevulin A induces apoptosis and shows anticancer activity.

Polθ-IN-5 (Compound 139) is a DNA polymerase theta (Polθ) inhibitor. Polθ-IN-5 has antitumor activity.

(±)-Dehydroaltenusin, an antibiotic, is a selective eukaryotic DNA polymerase α (pol α) inhibitor with an IC₅₀ of 0.68 μM. (±)-Dehydroaltenusin can be isolated from fungus Alternaria tenuis. (±)-Dehydroaltenusin competitively inhibits the DNA template primer (K_i: 0.23 μM) and non-competitively suppresses the 2'-deoxyribonucleoside 5'-triphosphate substrate (K_i: 0.18 μM). (±)-Dehydroaltenusin induces the cancer cell S-phase cycle arrest and apoptosis. (±)-Dehydroaltenusin can be used for cancers like human adenocarcinoma research.

Lucidenic acid O is a terpene compound, is a DNA polymerases inhibitor. 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.

Phosphonoacetic acid sodium is a potent antiviral agent. Phosphonoacetic acid sodium inhibits a variety of herpesviruses, orthopoxviruses, and retroviruses. Phosphonoacetic acid sodium strongly inhibits viral and cellular DNA polymerase, reverse transcriptase, and terminal deoxynucleotidyl transferase activities in a non-competitive or uncompetitive manner by binding to the pyrophosphate site of the enzyme. Phosphonoacetic acid sodium is useful for research related to lymphoid leukemia, herpesvirus infection, and vaccinia virus skin lesions.

Soulattrolide is a non-nucleoside HIV-1 reverse transcriptase (RT) inhibitor with IC₅₀ values of 0.34 µM for HIV-1 RT, 69.5 µM for E. coli RNase H, and >495 µM for human DNA polymerase β, and can be found in Calophyllum teysmannii latex. Soulattrolide can be used for the research of HIV-1 infection, pain, inflammation, and Mycobacterium tuberculosis infection.

ART558 (GMP) is ART558 (HY-141520) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. ART558 is a potent, selective and allosteric DNA polymerase theta (Polθ) inhibitor (IC₅₀=7.9 nM). ART558 elicits BRCA-gene synthetic lethality and DNA damage. ART558 can be used for the research of cancer, such as breast cancer.