DNA Polymerases Inhibitor

ddCTP trilithium is a type of chain-terminating deoxynucleotide. ddCTP trilithium can be incorporated into the extension primer chain that lacks the 3'-hydroxyl group, thereby terminating primer extension, viral genome replication, and DNA synthesis. ddCTP trilithium can distinguish almost identical RNA through distinguishable extension products in primer extension inhibition experiments. ddCTP trilithium is the active metabolite of Zalcitabine (HY-17392), which can competitively inhibit HIV reverse transcriptase, terminate the synthesis of viral DNA chains, and thereby inhibit HIV replication.

Morindone is an anthraquinone found in Morinda citrifolia L. Morindone can inhibit cancer cells proliferation, induce apoptosis and cause G1 phase arrest. Morindone can inhibit activities of DNA polymerase and downregulate mutated TP53 and KRAS gene expression. Morindone can be used for the research of cancer, such as colon cancer.

Eprociclovir is an antiviral drug with nucleoside analogues. The triphosphate form of Eprociclovir is converted into the active form within virus-infected cells by the virus and possible cellular enzymes, including the viral thymidine kinase, thereby inhibiting the activity of the viral DNA polymerase. The primary activity of Eprociclovir is against herpes viruses, including but not limited to cytomegalovirus (CMV) and herpes simplex virus (HSV). Eprociclovir can be used in studies interfered with by sensitive viruses.

Petasiphenol is a phenolic natural product found in Petasites japonicus, possessing selective inhibitory activity against DNA polymerase λ. Petasiphenol binds to the N-terminal BRCT domain of DNA polymerase λ, with an IC₅₀ of 7.8 μM against DNA polymerase λ. Petasiphenol induces cell growth inhibition, G1 phase cell cycle arrest in human cancer cell lines, and exhibits anti-inflammatory activity against TPA-induced mouse ear inflammation. Petasiphenol can be used for research on cancer and inflammation-related diseases.

Multi-target kinase-IN-9 is a multi-target enzyme inhibitor with antiproliferative and antiangiogenic activities, and exhibits remarkable selectivity against hepatocellular carcinoma cells. By broadly binding to the active sites or ATP-binding regions of multiple key enzymes including DNA polymerase β, Pyruvate Kinase M2 (PKM2), Multi-target kinase-IN-9 comprehensively disrupts DNA repair and replication, glycolysis, chromatin dynamics and transcriptional programs, and blocks the self-renewal of cancer stem cells. Multi-target kinase-IN-9 induces genomic instability, lysosomal dysfunction and autophagic flux impairment, thereby triggering tumor cell death, effectively inhibiting tumor proliferation, invasion, metastasis and angiogenesis, and significantly reducing tumor volume in xenograft models. Multi-target kinase-IN-9 is applicable to hepatocellular carcinoma-related research.

Polθ-IN-6 (Compound 89) is a DNA polymerase theta (Polθ) inhibitor. Polθ-IN-6 has antitumor activity.

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.

Procyanidin B3-3-O-gallate (3-O-Galloylprocyanidin B3) is a selective mammalian DNA polymerase α inhibitor, with a calf DNA polymerase α IC₅₀ of 0.26 μM. Procyanidin B3-3-O-gallate scavenges DPPH radicals. Procyanidin B3-3-O-gallate can be used for research on oxidative stress and inflammatory diseases^[1].

DNA polymerase-IN-7 is a noncompetitive inhibition of DNA Polymerase β with an IC₅₀ of 112 nM and a K_i of 35 nM. DNA polymerase-IN-7 can inhibit DNA pol β lyase activity and the binding of the lyase domain of Pol β to DNA. DNA polymerase-IN-7 can be used for the research of cancer, such as cervical cancer.

Polθ-IN-9 is an orally active Polθ polymerase inhibitor (IC₅₀ = 9.6 nM, K_d = 47.5 nM). Polθ-IN-9 shows remarkable selectivity with no inhibitory activity against other human DNA polymerases, including Pol α, Pol ε, Pol γ, Pol λ, and Pol μ. Polθ-IN-9 exhibits strong antiproliferative activity in DLD1 BRCA2 KO cells (IC₅₀ = 2.9 μM), and high sensitivity to MDA-MB-436 cells (IC₅₀ = 4.9 μM). Polθ-IN-9 increases DNA damage accumulation, induces γH2AX levels, and inhibits tumor growth in combination with Olaparib (HY-10162), in the MDA-MB-436 xenograft model. Polθ-IN-9 can be used for the research of homologous recombination (HR)-deficient cancers such as breast cancer.

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

Polθ-IN-11 is an orally active DNA polymerase θ (Polθ) ATPase inhibitor with an IC₅₀ of 4.3 nM against human targets. Polθ-IN-11 activates the cGAS-STING pathway. Polθ-IN-11 upregulates the expression of PD-L1 in HR-deficient cancer cells. Polθ-IN-11 acts synergistically with PARP inhibition in HR-deficient cancer cells and in vivo xenograft models. Polθ-IN-11 can be used in studies related to HR-deficient cancers.

BVDU 5′-Triphosphate is an antivirus agent with 5′-Triphosphate label, targeting viral DNA polymerase. BVDU 5′-Triphosphate shows excellent selectivity against varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1), due to a specific phosphorylation by the virus-encoded thymidine kinase.

DNA polymerase-IN-3 (Compd 5b) is a coumarin derivative that exhibits inhibitory activity against Taq DNA polymerase and can be used in proliferative disease research.

NSC666715 is a DNA polymerase β (Pol-β) inhibitor. NSC666715 directly and specifically interacts with Pol-β, interferes with its binding to damaged DNA, blocks its dRP lyase activity, and inhibits Pol-β-mediated SN- and LP-BER. NSC666715 induces AP site accumulation and S-phase cell cycle arrest, and triggers senescence and apoptosis (apoptosis) via the p53/p21 pathway in colorectal cancer cells. NSC666715 enhances TMZ (HY-17364)-induced DNA damage, senescence and apoptosis, and potentiates the cytotoxicity of TMZ. NSC666715 inhibits tumor growth in colon cancer xenograft models. NSC666715 can be used in research related to colorectal cancer.

Fazarabine (Kymarabine; Ara-AC; NSC 281272) is an orally active, blood-brain barrier permeable DNA polymerase inhibitor and antitumor agent. Fazarabine interferes with DNA synthesis via intracellular activation into a triphosphate nucleotide that directly incorporates into DNA, inducing cytotoxicity, myelosuppression, as well as moderate nausea and vomiting. Fazarabine is resistant to deamination by cytidine-deoxycytidine deaminase and undergoes spontaneous aqueous degradation. Fazarabine exerts time-dependent, broad-spectrum activity against leukemia and solid tumors. Fazarabine can be used in research related to refractory malignancies, acute leukemia, and blast-phase chronic myeloid leukemia.

Anti-MRSA agent 28 is an antibacterial agent against multidrug resistant (MDR) gram-positive strains with MICs of 0.06-0.125 μg/mL. Anti-MRSA agent 28 can target DNA polymerase IIIC to reduce the amount of genomic DNA with the IC₅₀ of 3.80 μg/mL. Anti-MRSA agent 28 has good antibacterial activity and reduces inflammation. Anti-MRSA agent 28 can be used against gram-positive strains and infectious conditions.

Ibezapolstat hydrochloride is a first-in-class, orally active DNA polymerase IIIC (pol IIIC) inhibitor, with a K_i of 0.325 μM for the DNA pol IIIC from C. difficile. Ibezapolstat hydrochloride is developed for the research of C. difficile infection(CDI).

Rifamycin AF-013 is a derivative of Rifamycin (HY-B1907). Rifamycin AF-013 inhibits DNA polymerase γ by competing with dTTP and template primers for binding. Rifamycin AF-013 exhibits inhibitory activity against Rifampicin (HY-B0272)-resistant RNA polymerase. Rifamycin AF-013 inhibits non-polymerase enzymes including glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and Alkaline phosphatase. Rifamycin AF-013 can be used in research related to Rifampicin-resistant bacterial infections and Ehrlich ascites tumors.

ddATP (lithium) (2',3'-Dideoxyadenosine 5'-triphosphate (lithium)) is an active metabolite of 2',3'-dideoxyinosine and a DNA polymerase chain elongation inhibitor. ddATP (lithium) is used in Sanger DNA sequencing and in research related to viral infection^{[1][2][3][4][5]}.