Page last updated: 2024-12-10
merbarone
Description
Research Excerpts
Clinical Trials
Roles
Classes
Pathways
Study Profile
Bioassays
Related Drugs
Related Conditions
Protein Interactions
Research Growth
Market Indicators
Description
merbarone: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
Cross-References
| ID Source | ID |
|---|---|
| PubMed CID | 4990817 |
| CHEMBL ID | 1765797 |
| SCHEMBL ID | 10817881 |
| MeSH ID | M0132159 |
Synonyms (26)
| Synonym |
|---|
| 97534-21-9 |
| merbarone |
| merbarone, >=98% (hplc), solid |
| nsc 336628 |
| 5-pyrimidinecarboxamide, hexahydro-4,6-dioxo-n-phenyl-2-thioxo- |
| NCGC00165827-01 |
| 5-(n-phenylcarboxamido)-2-thiobarbituric acid |
| HSCI1_000067 |
| CHEMBL1765797 , |
| ywb9if596v , |
| unii-ywb9if596v |
| ccris 8215 |
| 5-(n-phenylcarbamoyl)-2-thiobarbituric acid |
| FT-0630995 |
| SCHEMBL10817881 |
| DTXSID9031567 |
| hexahydro-4,6-dioxo-n-phenyl-2-thioxo-5-pyrimidinecarboxamide |
| us9428466, merbarone |
| bdbm241949 |
| 4,6-dioxo-n-phenyl-2-thioxohexahydropyrimidine-5-carboxamide |
| merbarone - cas 97534-21-9 |
| MS-23710 |
| XDA53421 |
| CS-0014735 |
| HY-19024 |
| AKOS040748903 |
Research Excerpts
Overview
Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. Merbarone is a catalytic inhibitor of DNA topoisomerase (topo) II that does not stabilize DNA-topo II cleavable complexes.
Effects
| Excerpt | Reference | Relevance |
|---|---|---|
| "Merbarone has previously been shown to have antitumor activity of unknown mechanism in P388 and L1210 tumor models (A. " | ( In vitro and intracellular inhibition of topoisomerase II by the antitumor agent merbarone. Bartus, JO; Drake, FH; Hertzberg, RP; Hofmann, GA; Johnson, RK; Mattern, MR; Mirabelli, CK; Mong, SM, 1989) | 1.95 |
Actions
| Excerpt | Reference | Relevance |
|---|---|---|
| "Merbarone failed to increase colony formation." | ( Effects of DNA topoisomerase II inhibitors on human bone marrow progenitor cells. Berney, JJ; Chresta, CM; Delgado, C; Francis, GE; Patel, P; Tejedor, MC, 1994) | 1.01 |
Dosage Studied
| Excerpt | Relevance | Reference |
|---|---|---|
| " Preclinical studies suggested that the antitumor effects of this drug were schedule dependent, since repeated dosing increased killing of tumor cells when compared to intermittent injections." | ( Phase I clinical and pharmacological study of merbarone. Baltzer, L; Dimaggio, JJ; Haines, I; Lee, SJ; Lowenthal, DA; Muindi, J; Stevens, YW; Walsh, TD; Warrell, RP; Yaldaei, S, 1990) | 0.54 |
| " Seventeen patients were treated at a starting dose of 1000 mg/m2/day for 5 days by continuous intravenous infusion; the dose was escalated in accordance with the toxicity experienced, and no dosage reductions owing to toxicity were required." | ( A phase II study of merbarone in patients with adenocarcinoma of the pancreas. Ajani, JA; Daugherty, KR; Jones, DV; Krakoff, IH; Levin, B; Winn, RJ, 1993) | 0.61 |
| " Etoposide was administered at a dosage of 30 or 60 mg/kg." | ( Dominant lethal mutations of topoisomerase II inhibitors etoposide and merbarone in male mice: a mechanistic study. Attia, SM, 2012) | 0.61 |
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Protein Targets (3)
Inhibition Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| DNA topoisomerase 2-alpha | Homo sapiens (human) | IC50 (µMol) | 51.6000 | 0.4800 | 4.3564 | 9.9400 | AID1471728; AID1547964; AID1547965; AID591712; AID779597 |
| Xanthine dehydrogenase/oxidase | Homo sapiens (human) | IC50 (µMol) | 274.0000 | 0.0013 | 2.8138 | 9.8200 | AID1649927 |
| Solute carrier family 22 member 12 | Homo sapiens (human) | IC50 (µMol) | 5.4000 | 0.0260 | 2.6152 | 7.3000 | AID1649928 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (52)
Molecular Functions (24)
Ceullar Components (21)
Bioassays (40)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1434589 | Inhibition of human topoisomerase-2 alpha expressed in baculovirus infected insect cells assessed as reduction in enzyme-meditaed supercoiled pRYG DNA substrate relaxation at 100 uM in presence of buffer containing DTT after 30 mins by agarose gel electro | 2017 | Bioorganic & medicinal chemistry letters, 02-01, Volume: 27, Issue:3 | Synthesis and biological evaluation of naphthoquinone-coumarin conjugates as topoisomerase II inhibitors. |
| AID779597 | Inhibition of human topoisomerase 2alpha-mediated relaxation of supercoiled pBR322 after 1 hr by ethidium bromide staining | 2013 | Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21 | Further SAR studies on bicyclic basic merbarone analogues as potent antiproliferative agents. |
| AID1471733 | Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID1079941 | Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source] | |||
| AID1547964 | Inhibition of human topo2alpha incubated for 30 mins by SYBR safe DNA stain based decatenation assay | 2020 | Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7 | Design, Synthesis, Dynamic Docking, Biochemical Characterization, and |
| AID1079945 | Animal toxicity known. [column 'TOXIC' in source] | |||
| AID1079934 | Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source] | |||
| AID1079938 | Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source] | |||
| AID1471734 | Antiproliferative activity against human A549 cells after 72 hrs by MTT assay | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID1547967 | Antiproliferative activity against human HeLa cells by MTT assay | 2020 | Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7 | Design, Synthesis, Dynamic Docking, Biochemical Characterization, and |
| AID1471732 | Antiproliferative activity against human HeLa cells after 72 hrs by MTT assay | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID1079943 | Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source] | |||
| AID1079939 | Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source] | |||
| AID1079931 | Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source] | |||
| AID1471727 | Poison activity at human Topo2alpha expressed in baculovirus-infected insect cells using pBR322 as substrate assessed as topo2/DNA cleavage complex generation after 6 minutes by ethidium bromide staining based agarose gel electrophoresis | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID1434590 | Inhibition of human topoisomerase-2 alpha expressed in baculovirus infected insect cells assessed as reduction in enzyme-meditaed supercoiled pRYG DNA substrate relaxation at 100 uM in presence of buffer containing 2-mercaptoethanol after 30 mins by agaro | 2017 | Bioorganic & medicinal chemistry letters, 02-01, Volume: 27, Issue:3 | Synthesis and biological evaluation of naphthoquinone-coumarin conjugates as topoisomerase II inhibitors. |
| AID1079936 | Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source] | |||
| AID1079942 | Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source] | |||
| AID779718 | Cytotoxicity against human HeLa cells | 2013 | Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21 | Further SAR studies on bicyclic basic merbarone analogues as potent antiproliferative agents. |
| AID591712 | Inhibition of human topoisomerase 2 alpha-mediated relaxation of supercoiled pHOT DNA after 30 mins by agarose gel electrophoresis | 2011 | Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7 | Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes. |
| AID1079949 | Proposed mechanism(s) of liver damage. [column 'MEC' in source] | |||
| AID1471730 | Binding affinity to calf thymus DNA at 50 uM by UV-spectrophotometric analysis | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID1547965 | Inhibition of human topo2alpha by plasmid relaxation assay | 2020 | Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7 | Design, Synthesis, Dynamic Docking, Biochemical Characterization, and |
| AID1079946 | Presence of at least one case with successful reintroduction. [column 'REINT' in source] | |||
| AID1547966 | Antiproliferative activity against human DU145 cells by MTT assay | 2020 | Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7 | Design, Synthesis, Dynamic Docking, Biochemical Characterization, and |
| AID1547968 | Antiproliferative activity against human A549 cells by MTT assay | 2020 | Journal of medicinal chemistry, 04-09, Volume: 63, Issue:7 | Design, Synthesis, Dynamic Docking, Biochemical Characterization, and |
| AID1079947 | Comments (NB not yet translated). [column 'COMMENTAIRES' in source] | |||
| AID1079937 | Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source] | |||
| AID1079944 | Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source] | |||
| AID1079932 | Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source] | |||
| AID1079935 | Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source] | |||
| AID779719 | Cytotoxicity against human MCF7 cells | 2013 | Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21 | Further SAR studies on bicyclic basic merbarone analogues as potent antiproliferative agents. |
| AID1079948 | Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source] | |||
| AID1649927 | Inhibition of human xanthine oxidase | 2019 | European journal of medicinal chemistry, Mar-15, Volume: 166 | Pharmacological urate-lowering approaches in chronic kidney disease. |
| AID1649928 | Inhibition of human URAT1 | 2019 | European journal of medicinal chemistry, Mar-15, Volume: 166 | Pharmacological urate-lowering approaches in chronic kidney disease. |
| AID1079933 | Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is | |||
| AID1471735 | Antiproliferative activity against human DU145 cells after 72 hrs by MTT assay | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID1471728 | Inhibition of human topoisomerase 2alpha expressed in baculovirus-infected insect cells assessed as reduction in pBR322 supercoiled DNA relaxation after 60 mins by ethidium bromide staining based agarose gel electrophoresis | 2018 | Journal of medicinal chemistry, 02-08, Volume: 61, Issue:3 | Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity. |
| AID779720 | Cytotoxicity against human MT4 cells | 2013 | Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21 | Further SAR studies on bicyclic basic merbarone analogues as potent antiproliferative agents. |
| AID1079940 | Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source] | |||
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
Research
Studies (69)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 8 (11.59) | 18.7374 |
| 1990's | 31 (44.93) | 18.2507 |
| 2000's | 14 (20.29) | 29.6817 |
| 2010's | 12 (17.39) | 24.3611 |
| 2020's | 4 (5.80) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Market Indicators
Research Demand Index: 25.12
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (25.12) All Compounds (24.57) |
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 11 (14.86%) | 5.53% |
| Reviews | 3 (4.05%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 60 (81.08%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||