Topoisomerase

Doxorubicin hydrochloride (Adriamycin) belongs to the anthracycline class of antibiotics and is an inhibitor of human DNA topoisomerase I II (IC50=0.8 2.67 μM). Doxorubicin hydrochloride exhibits cytotoxicity and antitumor activity. Doxorubicin hydrochloride reduces the phosphorylation of AMPK and its downstream target protein acetyl coenzyme A carboxylase, and induces apoptosis and autophagy.

Trovafloxacin is a broad-spectrum fluoroquinolone antibiotic that inhibits the activity of DNA gyrase and topoisomerase IV, enzymes involved in DNA replication. It also acts as an effective and specific inhibitor of the pannexin 1 channel (PANX1, IC50 = 4 μM).

XR 5944 is an antitumor compound that targets DNA, is a topoisomerase inhibitor, inhibits ER activity, and can be used to study colon and lung cancer.

Exatecan (DX-8951f) is a DNA topoisomerase I (TOP1) inhibitor with an IC50 value of 2.2 μM (0.975 μg/mL).Exatecan has antitumor activity and may be used in cancer research.

Suramin Sodium Salt (BAY-205) is a sodium salt form of suramin, a polysulphonated naphthylurea with potential antineoplastic activity. Suramin blocks the binding of various growth factors, including insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor growth factor-beta (TGF-beta), to their receptors, thereby inhibiting endothelial cell proliferation and migration. This agent also inhibits vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis; retroviral reverse transcriptase; uncoupling of G-proteins from receptors; topoisomerases; cellular folate transport; and steroidogenesis.

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

Ellipticine (Elliptisine) is a potent antineoplastic agent exhibiting multiple mechanisms of action, IC50 of 0.67±0.06, 1.25±0.13, 1.25±0.13, 0.67±0.06, 0.27±0.02, 0.49±0.04, 0.44±0.03, and 1.48±0.62 μM for Leukemia HL-60, Breast adenocarcinoma MCF-7, Breast adenocarcinoma MCF-7, Leukemia HL-60, Neuroblastoma IMR-32, Neuroblastoma UKF-NB-4, Neuroblastoma UKF-NB-3, and Glioblastoma U87 mg cell, respectively.

Zoliflodacin (ETX0914) (ETX0914, AZD0914) is a new bacterial DNA gyrase/topoisomerase inhibitor. Zoliflodacin has potent in vitro antibacterial activity against Gram-positive and Gram-negative organisms, including S. aureus (MIC90: 0.25 μg/mL).

Etoposide (VP-16-213) is a topoisomerase II inhibitor that inhibits DNA synthesis by forming a complex with topoisomerase II and DNA (IC50=60.3 μM). Etoposide has antitumor activity and induces apoptosis and autophagy.

Dxd (OQM5SD32BQ) is a potent inhibitor of DNA topoisomerase I with an IC50 of 0.31 μM. It is used as a conjugated drug of HER2-targeting ADC.

Ledoxantrone trihydrochloride is a Top II inhibitor with anticancer activity and is used in the study of digestive disorders and urologic disorders.

Aldoxorubicin hydrochloride is an albumin-binding prodrug of Doxorubicin, a DNA topoisomerase II inhibitor. Aldoxorubicin hydrochloride is released from albumin under acidic conditions. Aldoxorubicin hydrochloride exhibits potent antitumor activities in various cancer cell lines and in murine tumor models.

SN-38 (NK012) is the active metabolite of Irinotecan, a DNA topoisomerase I (Topo I) inhibitor, which inhibits DNA and RNA synthesis (IC50=0.077/1.3 μM). SN-38 has antitumor activity and induces autophagy.

Epirubicin hydrochloride (Pharmorubicin) is an adriamycin derivative, a topoisomerase (Topo) inhibitor, and a Forkhead box protein p3 (Foxp3) inhibitor. Epirubicin hydrochloride has antitumor activity.

F-14512 (free base) is a topoisomerase II inhibitor for the study of acute myeloid leukemia.

Topotecan (NSC-609669) is a Topoisomerase I inhibitor,and is an antineoplastic agent used to treat ovarian cancer that works by inhibiting DNA topoisomerases.

Irinotecan (CPT-11), a derivative of camptothecin, is an inhibitor of DNA topoisomerase I (Topo I). Irinotecan has antitumor activity by preventing DNA strand reattachment through binding to the Topo I complex, resulting in double-stranded DNA breaks and cell death.

Pirarubicin (Theprubicin) is an anthracycline antibiotic. It is also a DNA RNA synthesis inhibitor that intercalates into DNA and interacts with topoisomerase II, utilized as an antineoplastic agent.

Simmitecan hydrochloride is a camptothecin derivative, a topoisomerase I inhibitor with anticancer activity, which can be used to study is solid tumors.

β-Lapachone (ARQ-501) is a specific DNA topoisomerase I inhibitor, and no inhibitory activities against DNA topoisomerase II or ligase.

Daunorubicin hydrochloride (Rubidomycin hydrochloride), an anthracycline aminoglycoside antineoplastic, inhibits DNA replication and repair and RNA and protein synthesis.

Leurubicin (N-Leucyldoxorubicin) is a potential Top II inhibitor for the study of bacterial infections .

Mitoxantrone (mitozantrone) is an anthracenedione antibiotic with antineoplastic activity. Mitoxantrone intercalates into and crosslinks DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, resulting in DNA strand breaks and inhibition of DNA repair. Mitoxantrone is less cardiotoxic compared to doxorubicin.

IndiMitecan (LMP776) is an inhibitor of topoisomerase I (Top1) with anticancer activities [1].

Levofloxacin ((-)-Ofloxacin) is a synthetic fluoroquinolone antibiotic that inhibits the superhelical activity of bacterial DNA rotamase and prevents DNA replication. Levofloxacin is a broad-spectrum antibiotic used for the treatment of a wide range of bacterial infections.

Ellagic acid (Gallogen), a thickened tetracyclic natural product, is a potent CK2 inhibitor (IC50=40 nM; Ki=20 nM) with ATP-competitive properties. Ellagic acid is an antioxidant and also possesses antiproliferative activity.

Bisantrene (CL216942) is an anthracenyl bishydrazone with antineoplastic activity. Bisantrene intercalates with and disrupts the configuration of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in activity, but unlike doxorubicin, does not exhibit cardiotoxicity.

Ciprofloxacin monohydrochloride (Bay-09867 hydrochloride) is a broad-spectrum antimicrobial carboxyfluoroquinoline.

XR-11576 HCl is a novel orally active dual topoisomerase I and II inhibitor with antitumor activity.

DRF-1042, an orally active camptothecin analog, exhibits anticancer and insecticidal activities by inhibiting DNA topoisomerase I. It has been studied for its efficacy against solid tumors, including prostate and colon cancers.

Ciprofloxacin (Bay-09867), a synthetic broad spectrum fluoroquinolone antibiotic, inhibits bacterial DNA gyrase. It is more active against Gram-negative bacteria than Gram-positive bacteria.

Idarubicin hydrochloride (Zavedos), a hydrochloride salt form of Idarubicin, is a DNA topoisomerase II (topo II) inhibitor for MCF-7 cells ( IC50: 3.3 ng mL).

Topotecan hydrochloride (NSC609699) is an antineoplastic agent used to treat ovarian cancer.

Irinotecan Hydrochloride (CPT-11 hydrochloride) is the hydrochloride salt of a semisynthetic derivative of camptothecin. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Because ongoing DNA synthesis is necessary for irinotecan to exert its cytotoxic effects, it is classified as an S-phase-specific agent.

Gimatecan (STI481) is a potent topoisomerase I inhibitor. Gimatecan is an orally bioavailable camptothecin analogue with antitumor activity.

Novobiocin Sodium (Albamycinsodium) binds to DNA gyrase and blocks adenosine triphosphatase (ATPase) activity. Novobiocin sodium is an antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin.

9-Methoxycamptothecin (MCPT) has antitumour activities through topoisomerase inhibition.

Camptothecin (CPT) belongs to the alkaloid group of natural products and is a specific DNA topoisomerase I (Topo I) inhibitor (IC50=679 nM) with specificity. Camptothecin has antitumor activity and induces apoptosis.

Groenlandicine is a protoberberine alkaloid from Coptidis Rhizoma. Groenlandicine exhibits moderate inhibitory effect with IC50 value of 154.2 μM for human recombinant aldose reductase (HRAR). Groenlandicine selectively induces topoisomerase I-mediated DN

Berberine chloride (Natural Yellow 18) is an alkaloid from Hydrastis canadensis L., Berberidaceae and also found in many other plants. It is relatively toxic to parenterally but has been used orally for various fungal and parasitic infections and an anti-diarrheal.

LMP744 hydrochloride (NSC-706744 hydrochloride) is a DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity. 

Mitoxantrone dihydrochloride (NSC-301739) is the hydrochloride salt of an anthracenedione antibiotic with antineoplastic activity. It is a type II topoisomerase inhibitor.

Irinotecan hydrochloride trihydrate (CPT-11 HCl Trihydrate) keeps DNA from unwinding by inhibiting topoisomerase 1.

1. Nitidine chloride has inhibitory effects on various tumors, such as renal cancer , breast cancer. 2. Nitidine chloride inhibits the proliferation of SMMC-7721 cells in vitro in a time- and dose-dependent manner and identifies efficacy in vivo in a mouse model of HCC.

PNU-159682, a metabolite of anthracycline neomycin, is a DNA topoisomerase II inhibitor with excellent cytotoxicity.

Aurintricarboxylic acid (NSC-4056) is a strong inhibitor of topoisomerases and other nucleases. It is a potent inhibitor of ribonuclease and topoisomerase II by preventing the binding of the nucleic acid to the enzyme.

Betulinic acid (ALS-357) is a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase.

Aclacinomycin A (Aclarubicin) is a novel anthracycline antibiotic isolated from Streptomyces galilei with antitumor activity.Aclacinomycin A is an inhibitor of topoisomerases I and II and inhibits RNA activity.Aclacinomycin A has been used in the study of relapsed leukemia and advanced malignant lymphomas.

EIDD-1931 (Beta-d-N4-hydroxycytidine) is a ribonucleoside analog with antiviral activity that inhibits the replication of severe acute respiratory syndrome coronavirus [SARS-CoV] in Vero 76 cells, Middle East respiratory syndrome coronavirus [MERS-CoV] in Calu-3 2B4 cells, and SARS-CoV-2 in Vero cells (IC50s = 0.1, 0.15, and 0.3 μM, respectively).

Amsacrine (AMSA) (mAMSA) an antineoplastic agent which can intercalate into the DNA of tumor cells. Amsacrine also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II.