DNA/RNA Synthesis Inhibitor

Idarubicin is an orally active and potent anthracycline antileukemic agent. Idarubicin inhibits the topoisomerase II interfering with the replication of DNA and RNA transcription. Idarubicin shows induction of DNA damage. Idarubicin inhibits DNA synthesis and of c-myc expression. Idarubicin inhibits the growth of bacteria and yeasts.

Pyridostatin (RR82) TFA is a G-quadruplex (G4) inducer/stabilizer with a K_d of 490 nM. Pyridostatin TFA also acts as an inhibitor of Zika virus (ZIKV) NS2B-NS3 protease, with an IC₅₀ of 11.0 μM. Pyridostatin TFA interacts with G-quadruplex structures, regulates the expression of SRC and SUB1, and induces replication- and transcription-dependent DNA damage, growth arrest, and genomic instability. Pyridostatin TFA exhibits antiproliferative and antiviral activities. Pyridostatin TFA can be used in studies related to breast cancer, cervical cancer, and Zika virus infection.

Amotosalen hydrochloride (S-59) is a light-activated, DNA-, RNA-crosslinking psoralen compound, which is used to neutralise pathogens. Light-activated Amotosalen binds and permanently crosslinks DNA, preventing replication and thus stopping proliferation of donor T cells. Amotosalen can be used for the study of blood system pathogen reduction technology and graft-versus-host disease (GVHD).

Methoxyamine (O-Methylhydroxylamine) hydrochloride is an orally active and potent base excision repair (BER) inhibitor. Methoxyamine hydrochloride binds to 3’ hydroxyl groups that are left behind by 3-methylpurine-DNA glycosylase (MPG) following excision of the damaged base and thus inhibits BER activity. Methoxyamine hydrochloride binds directly to the apyrimidinic (AP) sites. Methoxyamine hydrochloride synergistically enhances the therapeutic efficacy of DNA-damaging agents.

SSI-4 is an orally active stearoyl-CoA desaturase (SCD1) inhibitor with an EC₅₀ of 1.9 nM against mouse SCD1. SSI-4 blocks the conversion of saturated fatty acids to monounsaturated fatty acids, reducing the production of oleic acid and palmitoleic acid. SSI-4 induces lipid peroxidation, endoplasmic reticulum stress, DNA damage and activates apoptotic mechanisms. SSI-4 inhibits mTORC1 activity, suppresses B cell proliferation and antibody production, and induces autophagy. SSI-4 is applicable to research on cancers such as acute myeloid leukemia and renal cell carcinoma, as well as influenza infections.

Gimeracil, a component of an oral fluoropyrimidine derivative S-1, inhibits DNA DSB repair and is a potent inhibitor of DPYD (dihydropyrimidine dehydrogenase, DPD).

Pyrazofurin is an antitumor pyrimidine nucleoside analogue and a orotate-phosphoribosyltransferase inhibitor. Pyrazofurin inhibits cell proliferation and intracellular DNA synthesis by inhibiting uridine 5'-phosphate synthase. Pyrazofurin is also an antibiotic with a broad spectrum of antiviral activity.

YTHDC1-IN-1 is a selective YTHDC1 inhibitor with a K_d of 49 nM and an IC₅₀ of 0.35 μM. YTHDC1-IN-1 can inhibit the proliferation and induce apoptosis of acute myeloid leukemia cell lines. YTHDC1-IN-1 has anti-tumor activity.

Guanosine triphosphate (GTP) trisodium salt hydrate is a critical nucleotide and regulator of cellular metabolism. Guanosine triphosphate trisodium salt hydrate promotes ribosomal DNA localization, pre-rRNA transcription and ribosome biogenesis by binding to RNA polymerase I and GPN proteins (GPN1/3). Guanosine triphosphate trisodium salt hydrate links MYC-dependent ribosome biogenesis to nucleotide sufficiency, acts as a metabolic gatekeeper supporting protein synthesis, DNA/RNA synthesis and cellular signal transduction, while also participating in the physiological activities of pancreatic β-cells and serving as an oxidative substrate for reactive oxygen species. In small cell lung cancer with high MYC expression, Guanosine triphosphate trisodium salt hydrate accumulates through the IMPDH-driven synthetic pathway, thereby affecting apoptosis and mitotic processes. Guanosine triphosphate trisodium salt hydrate is used in the research of small cell lung cancer, hepatoblastoma and cellular metabolism.

9-Amino-6-chloro-2-methoxyacridine (ACMA) is an acridine derivative and Fluorescent probe. 9-Amino-6-chloro-2-methoxyacridine inhibits viral replication, inhibits DNA synthesis and protein metabolism through cell cycle arrest, and induces lipid metabolism regulation, genotoxicity, mutagenicity, and cytotoxicity through DNA strand breaks. 9-Amino-6-chloro-2-methoxyacridine partially intercalates into DNA, forming three distinct complexes, stabilizes the DNA helix, and quenches fluorescence upon intercalation through electron transfer with guanine. 9-Amino-6-chloro-2-methoxyacridine monitors the generation and collapse of the proton motive force, H⁺ pumping by F₁F₀-ATP synthase, and the collapse of pH gradients in inverted membrane vesicles. 9-Amino-6-chloro-2-methoxyacridine shows potent anti-BVDV activity. 9-Amino-6-chloro-2-methoxyacridine can be used for research on bovine viral diarrhea virus infection, leishmaniasis, and MRSA infection.

Farudodstat (ASLAN003) is an orally active and potent Dihydroorotate Dehydrogenase (DHODH) inhibitor with an IC₅₀ of 35 nM for human DHODH enzyme. Farudodstat inhibits protein synthesis via activation of AP-1 transcription factors. Farudodstat induces apoptosis and substantially prolongs survival in acute myeloid leukemia (AML) xenograft mice.

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.

N-6-Methyl-2-deoxyadenosine (m6dA) is an adenine nucleoside analogue. N-6-Methyl-2-deoxyadenosine targets nuclear processes and DNA replication machineries including WER, SATB1, TFAM, Jumu, SSBP1, DNA polymerase η and phage polymerase Gp90 exo⁻. N-6-Methyl-2-deoxyadenosine acts as a multifunctional epigenetic regulator that modulates transcription, DNA damage response, cell cycle, transposon silencing, stress adaptation, epigenetic crosstalk, and nucleosome organization in both prokaryotes and eukaryotes. N-6-Methyl-2-deoxyadenosine regulates mitochondrial epigenetic inheritance and is required for fear extinction memory in mice. N-6-Methyl-2-deoxyadenosine exhibits dysregulated levels in cancers. N-6-Methyl-2-deoxyadenosine can be used for the research of glioblastoma, triple negative breast cancer, and conditioned fear (fear extinction impairment).

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-Fluoroadenine is a toxic purine bases. 2-Fluoroadenine has toxicity in nonproliferating and proliferating tumor cells. 2-Fluoroadenine can be used for researching anticancer.

Nedaplatin (NSC 375101D) is a derivative of cisplatin and DNA damage agent.

Cholesterol hemisuccinate (Cholesterol hydrogen succinate) Tris salt is a compound with hepatoprotective and anticancer activity. Cholesterol hemisuccinate Tris salt inhibits Acetaminophen (AAP) (HY-66005) hepatotoxicity, and prevents AAP-induced hepatic apoptosis and necrosis. Cholesterol hemisuccinate Tris salt inhibits DNA polymerase and DNA topoisomerase to inhibit DNA replication and repair and cell division. Cholesterol hemisuccinate Tris salt inhibits tumor growth. Cholesterol hemisuccinate Tris salt can be used for buffer preparation.

YK-4-279 blocks RNA Helicase A (RHA) binding with EWS-FLI1 (oncogenic protein). YK-4-279 induces apoptosis and shows anti-proliferation activities towards various cancer cells. YK-4-279 has a chiral center and it can be separated into two enantiomers. YK-4-279 can be used for the research of cancer.

PTC299 is an orally active inhibitor of VEGFA mRNA translation that selectively inhibits VEGF protein synthesis at the post-transcriptional level. PTC299 is also a potent inhibitor of dihydroorotate dehydrogenase (DHODH). PTC299 shows good oral bioavailability and lack of off-target kinase inhibition and myelosuppression. PTC299 can be useful for the research of hematologic malignancies.

APE1-IN-1 is a potent and blood-brain barrier (BBB) penetrant apurinic/apyrimidinic (AP) endonuclease 1 (APE1) inhibitor with an IC₅₀ value of 2 μM. APE1-IN-1 can potentiate the cytotoxicity of the alkylating agents Methylmethane sulfonate and Temozolomide (HY-17364) to cancer cells.