DNA/RNA Synthesis Inhibitor

Cynaroside (Luteolin 7-glucoside) is a flavonoid compound that exhibits anti-oxidative capabilities. Cynaroside is also a potent influenza RNA-dependent RNA polymerase inhibitor with an IC₅₀ of 32 nM. Cynaroside also is a promising inhibitor for H₂O₂-induced apoptosis, has cytoprotection against oxidative stress-induced cardiovascular diseases. Cynaroside also has antibacterial, antifungal and anticancer activities, antioxidant and anti-inflammatory activities.

Novobiocin (Albamycin; Cathomycin) is an orally active antibiotic and Hsp-90 antagonist that also inhibits the Polθ helicase/ATPase domain with IC₅₀ values of 24 μM and 15-17 μM, respectively. Novobiocin binds to Hsp90, GyrB, and POLθ, inhibiting their ATPase activity and ssDNA binding. Novobiocin inhibits molecular chaperone function and DNA repair, and induces apoptosis and genomic instability. Novobiocin exhibits bactericidal and antiparasitic activities. Novobiocin inhibits tumor growth in vivo. Novobiocin is used for research on equine piroplasmosis, ovarian cancer, breast cancer, anthrax, and melioidosis.

DNA2 inhibitor C5 is a potent, competitive, and specific DNA2 nuclease inhibitor with an IC₅₀ of 20 μM. DNA2 inhibitor C5 inhibits the nuclease, DNA-dependent ATPase, helicase, and DNA-binding activities of DNA2. DNA2 inhibitor C5 can be used in breast cancer and colorectal cancer research.

CB-6644 is a selective inhibitor of RUVBL1/2 complex with anti-cancer activity. CB-6644 blocks the ATPase activity of RUVBL1/2 with an IC₅₀ of 15 nM.

Docosanoic acid (Behenic acid) is a long-chain saturated fatty acid. Docosanoic acid inhibits the double-stranded DNA (dsDNA) binding activity of p53 DNA binding domain, with a K_d of 12 nM. Docosanoic acid has low bioavailability and can increase cholesterol in humans.

ML216 (CID-49852229) is a potent, selective and cell permeable inhibitor of the DNA unwinding activity of BLM helicase with IC₅₀s of 2.98 μM and 0.97 μM for BLM^full-length and BLM^636-1298, respectively. ML216 inhibits ssDNA-dependent ATPase activity of BLM with a K_i of 1.76 μM. Antitumor avtivity.

DL-alpha-Tocopherol is a synthetic vitamin E, with antioxidation effect. DL-alpha-Tocopherol protects human skin fibroblasts against the cytotoxic effect of UVB.

Daunorubicin (Daunomycin) is a topoisomerase II inhibitor with potent anti-tumor activity. Daunorubicin inhibits DNA and RNA synthesis. Daunorubicin is a cytotoxin that inhibits cancer cell viability and induces apoptosis and necrosis. Daunorubicin is also an anthracycline antibiotic. Daunorubicin can be used in the research of infection and variety of cancers, including leukemia, non-Hodgkin lymphomas, Ewing's sarcoma, Wilms' tumor.

Trifluridine (Trifluorothymidine) is an irreversible and orally active thymidylate synthase inhibitor, and thereby suppressing DNA synthesis. Trifluridine is an antiviral molecule used for research of HSV, rhabdovirus and orthopoxvirus infection. Trifluridine induces cell apoptosis and autophagy. Trifluridine is also an anticancer agent used in studies of metastatic colorectal cancer, gastrointestinal tumors.

Tambiciclib (GFH009, JSH-009) is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib can be used for AML research.

CX-5461 dihydrochloride is a selective, orally active RNA polymerase I inhibitor. CX-5461 dihydrochloride disrupts the formation of the SL1-rDNA complex, thereby blocking the transcription initiation of ribosomal RNA without altering the activity of RNA polymerase II, DNA replication, or protein translation processes. CX-5461 dihydrochloride upregulates the expression of p21, MDM2, Sestrin1/2, and phosphorylated AMPKα, and reduces the level of phosphorylated Akt. CX-5461 dihydrochloride induces G2/G2/M cell cycle arrest, Autophagy, Apoptosis, and cellular senescence, and activates CHK1, CHK2, and RPA. CX-5461 dihydrochloride can be used in research related to osteosarcoma, cervical cancer, hematologic malignancies, high-grade serous ovarian cancer, and solid tumors.

FDI-6 is an inhibitor of FOXM1. FDI-6 binds directly to FOXM1 protein, to displace FOXM1 from genomic targets in MCF-7 breast cancer cells, and induce concomitant transcriptional down-regulation.

6-Thio-2'-Deoxyguanosine is a nucleoside analogue that can be incorporated into de novo-synthesized telomeres by telomerase.

JH-RE-06, a potent REV1-REV7 interface inhibitor (IC₅₀=0.78 μM; K_d=0.42 μM), targets REV1 that interacts with the REV7 subunit of POLζ. JH-RE-06 disrupts mutagenic translesion synthesis (TLS) by preventing recruitment of mutagenic POLζ. JH-RE-06 improves chemotherapy.

Enitociclib ((+)-BAY-1251152; (+)-VIP152) is a selective CDK9 inhibitor (IC₅₀=3 nM) that inhibits transcriptional elongation by blocking Ser2/Ser5 phosphorylation of RNA polymerase II. Enitociclib specifically depletes key short-lived proteins such as c-MYC, MCL-1 and induces tumor cell apoptosis. Enitociclib also interferes with the production of enhancer RNAs (eRNA) and enhancer-promoter interactions, and downregulates oncogene expression at the epigenetic level. Enitociclib exerts synergistic effects with agents including Bortezomib (HY-10227), Lenalidomide (HY-A0003), Pomalidomide (HY-10984), Venetoclax (HY-15531) and Paclitaxel (HY-B0015), and even reverses paclitaxel resistance. Enitociclib serves as a vital research tool for various malignancies such as double-hit diffuse large B-cell lymphoma, multiple myeloma and pancreatic ductal adenocarcinoma.

7-Aminoactinomycin D (7-AAD) a cell-impermeant fluorescent DNA stain, is a potent RNA polymerase inhibitor. 7-Aminoactinomycin D selectively binds to GC regions of the DNA. 7-Aminoactinomycin D also has antibacterial effects.

Plitidepsin (Aplidine) is a potent anti-cancer agent by targeting eEF1A2 ( K_D=80 nM). Plitidepsin possesses antiviral activity and is against SARS-CoV-2 with an IC₉₀ of 0.88 nM. Plitidepsin is usually used for multiple myeloma and advanced cancer research, and has the potential for COVID-19 research.

Fidaxomicin (OPT-80), a macrocyclic antibiotic, is an orally active and potent RNA polymerase inhibitor. Fidaxomicin has a narrow spectrum of antibacterial activity and a good anti-Clostridium difficile activity (MIC₉₀=0.12 μg/mL). Fidaxomicin can be used for Clostridium difficile infection (CDI) research.

D-I03 is a selective RAD52 inhibitor with a K_d of 25.8 μM. D-I03 specifically inhibits RAD52-dependent single-strand annealing (SSA) and D-loop formation with IC₅₀s of 5 μM and 8 μM, respectively. D-I03 suppresses growth of BRCA1- and BRCA2-deficient cells and inhibits formation of damage-induced RAD52 foci, but does not effect on RAD51 foci induced by Cisplatin.

Madrasin (DDD00107587) is a splicing inhibitor that prevents formation of both splicing intermediates and products in vitro and interferes with one or more early steps in the pathway of spliceosome assembly. Madrasin also can inhibit pre-mRNA splicing in vitro and modify splicing of endogenous pre-mRNA in cells.