DNA/RNA Synthesis Inhibitor

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.

Plicamycin (Mithramycin A) is a selective specificity protein 1 (Sp1) inhibitor. Plicamycin inhibits the growth of various cancers by decreasing Sp1 protein. Plicamycin inhibits GSTM2 promoter activity and protein expression.

Levofloxacin ((-)-Ofloxacin) is an orally active antibiotic and is active against both Gram-positive and Gram-negative bacteria. Levofloxacin inhibits the DNA gyrase and topoisomerase IV. Levofloxacin can be used for chronic periodontitis, airway inflammation and BK Viremia research. Levofloxacin shows anti-orthopoxvirus activity.

Epirubicin hydrochloride (4'-Epidoxorubicin hydrochloride), a semisynthetic L-arabino derivative of doxorubicin, has an antineoplastic agent by inhibiting Topoisomerase. Epirubicin hydrochloride inhibits DNA and RNA synthesis. Epirubicin hydrochloride is a Forkhead box protein p3 (Foxp3) inhibitor and inhibits regulatory T cell activity.

Remdesivir (GS-5734) is a nucleoside analogue with effective antiviral activity. Remdesivir can inhibit the synthesis of viral DNA or RNA. Remdesivir can be used for the research of infection, such as SARS-CoV and MHV infection.

L-Asparaginase (L-ASNase) is a deamidating enzyme that catalyses the hydrolysis of L-asparagine and L-glutamine, and can be used for the research of acute lymphoblastic leukemia. L-Asparaginase depletes L-asparagine from plasma resulting in inhibition of RNA and DNA synthesis with the subsequent blastic cell apoptosis.

Floxuridine (5-Fluorouracil 2'-deoxyriboside) is a pyrimidine analog and known as an oncology antimetabolite. Floxuridine inhibits Poly(ADP-Ribose) polymerase and induces DNA damage by activating the ATM and ATR checkpoint signaling pathways in vitro. Floxuridine is a extreamly potent inhibitor for S. aureus infection and induces cell apoptosis. Floxuridine has antiviral effects against HSV and CMV.

Pyridostatin (RR82) hydrochloride is a G-quadruplex DNA stabilizing agent (K_d=490 nM) and can target DNA and RNA G4s in cells. Pyridostatin hydrochloride promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. Pyridostatin hydrochloride targets the proto-oncogene Src. Pyridostatin hydrochloride reduced SRC protein levels and SRC-dependent cellular motility in human breast cancer cells.

FAZ-3532 is a G3BP inhibitor (K_d = 0.54 μM) which binds to the NTF2L nsP3 binding pocket in G3BP1. FAZ-3532 disrupts the co-condensation of RNA, G3BP1, and caprin 1. FAZ-3532 inhibits G3BP-driven stress granule formation. FAZ-3532 can be studied as a powerful tool to probe the biology of stress granules and a promising interventions designed to modulate stress granule formation.

Halofuginone (RU-19110), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a K_i of 18.3 nM. Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Halofuginone is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca²⁺ channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects.

Guanosine triphosphate (GTP) disodium is a critical nucleotide and regulator of cellular metabolism. Guanosine triphosphate disodium promotes ribosomal DNA localization, pre-rRNA transcription and ribosome biogenesis by binding to RNA polymerase I and GPN proteins (GPN1/3). Guanosine triphosphate disodium 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 disodium accumulates through the IMPDH-driven synthetic pathway, thereby affecting apoptosis and mitotic processes. Guanosine triphosphate disodium is used in the research of small cell lung cancer, hepatoblastoma and cellular metabolism.

PolQi2 is a PolΘ inhibitor that targets and inhibits alt-EJ (alternative end-joining) repair by inhibiting the helicase domain at the N-terminus of PolΘ. PolQi2 enhances the precision and integration efficiency of gene editing at different loci and in various cell lines. Furthermore, the combined use of PolQi2 with DNA-PK inhibitors reduces the off-target effects of Cas9. PolQi2 can be used in gene editing research.

IMT1 is a first-in-class specific and noncompetitive human mitochondrial RNA polymerase (POLRMT) inhibitor. IMT1 causes a conformational change of POLRMT, which blocks substrate binding and transcription in a dose-dependent way in vitro. IMT1 reduces deoxynucleoside triphosphate levels and citric acid cycle intermediates, resulting in a marked depletion of cellular amino acid levels. IMT1 has the potential for mitochondrial transcription disorders related diseases.

Erythromycin is a macrolide antibiotic produced by actinomycete?Streptomyces erythreus?with a broad spectrum of antimicrobial activity. Erythromycin binds to bacterial 50S ribosomal subunits and inhibits?RNA-dependent protein synthesis?by blockage of transpeptidation and/or translocation reactions, without affecting synthesis of nucleic acid^[1][2]. Erythromycin also exhibits antitumor and neuroprotective effect in different fields of research^[3][4].

5-Fluorouridine, a metabolite of5-Fluorouracil (HY-90006), is a potent ribozyme self-cleavage inhibitor. 5-Fluorouridine incorporates into both total and poly A RNA and has antiproliferative activity. 5-Fluorouridine induces apoptosis.

ML-60218 is a broad-spectrum RNA pol III inhibitor, with IC₅₀s of 32 and 27 μM for Saccharomyces cerevisiae and human. ML-60218 disrupts already assembled viroplasms and to hamper the formation of new ones without the need for de novo transcription of cellular RNAs.

GC7 Sulfate is a deoxyhypusine synthase (DHPS) inhibitor.

Nitrochin (4-NQO) is a chemical carcinogen. Nitrochin induces oncostatin-M (OSM) in esophageal cells. Nitrochin induces DNA damage, and induces apoptosis via a p53-dependent mitochondrial signaling pathway.

Lurbinectedin (PM01183) is a DNA minor groove covalent binder with potent anti-tumour activity; inhibits RMG1 and RMG2 cell growth with IC₅₀ values of 1.25 and 1.16 nM, respectively.

HRO761 (Werner syndrome RecQ helicase-IN-1) (example 42) is a potent Werner syndrome RecQ DNA helicase enzyme (WRN) inhibitor and can be used in cancer research.