Piroxantrone is an anthracenedione-based anticancer drug that has been studied for its potential to treat various types of cancers. It was synthesized in the 1970s as an analog of the anticancer drug mitoxantrone, with the aim of improving its efficacy and reducing its side effects. Piroxantrone is a DNA topoisomerase II inhibitor, meaning it blocks the enzyme that is involved in the unwinding and re-winding of DNA during replication and transcription. This blockage leads to DNA damage and ultimately cell death. Research on piroxantrone has shown its effectiveness in treating cancers such as leukemia, lymphoma, and multiple myeloma. However, its clinical use has been limited due to concerns about its toxicity and the development of resistance. Despite these limitations, ongoing research explores new formulations and delivery methods for piroxantrone, aiming to optimize its therapeutic benefits and minimize its adverse effects.'
| ID Source | ID |
|---|---|
| PubMed CID | 59916 |
| CHEMBL ID | 203666 |
| SCHEMBL ID | 93599 |
| SCHEMBL ID | 7195166 |
| MeSH ID | M0135105 |
| Synonym |
|---|
| piroxantrona [inn-spanish] |
| piroxantrone [inn] |
| anthra(1,9-cd)pyrazol-6(2h)-one, 5-((3-aminopropyl)amino)-7,10-dihydroxy-2-(2-((2-hydroxyethyl)amino)ethyl)- |
| piroxantronum [inn-latin] |
| brn 4725135 |
| NCI60_003106 |
| pd-111815 |
| oxantrazole |
| dup-942 |
| nsc349174 |
| piroxantrone |
| (3-aminopropylamino)-dihydroxy-[2-(2-hydroxyethylamino)ethyl][?]one |
| 5-[(3-aminopropyl)amino]-7,10-dihydroxy-2-{2-[(2-hydroxyethyl)amino]ethyl}dibenzo[cd,g]indazol-6(2h)-one |
| NEURO_000181 |
| CHEMBL203666 , |
| bdbm50183475 |
| 5-(3-amino-propylamino)-7,10-dihydroxy-2-[2-(2-hydroxy-ethylamino)-ethyl]-2h-dibenzo[cd,g]indazol-6-one |
| yl4ty9wh22 , |
| 91441-23-5 |
| piroxantrona |
| piroxantronum |
| unii-yl4ty9wh22 |
| SCHEMBL93599 |
| 5-((3-aminopropyl)amino)-7,10-dihydroxy-2-(2-((2-hydroxyethyl)amino)ethyl)anthra(1,9-cd)pyrazol-6(2h)-one |
| SCHEMBL7195166 |
| bio4f4 |
| 5-((3-aminopropyl)amino)-7,10-dihydroxy-2-(2-((2-hydroxyethyl)amino)ethyl)dibenzo[cd,g]indazol-6(2h)-one |
| dup 942; ncs 349174; oxantrazole; pd 111815; |
| Q27294569 |
| 10-(3-aminopropylimino)-6,8-dihydroxy-14-[2-(2-hydroxyethylamino)ethyl]-14,15-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-1,4,6,8,11,13(16)-hexaen-3-one |
| DTXSID60869079 |
| 5-[(3-aminopropyl)amino]-6-hydroxy-2-{2-[(2-hydroxyethyl)amino]ethyl}-1,2-dihydrodibenzo[cd,g]indazole-7,10-dione |
Piroxantrone is an anthrapyrazole derivative with broad antitumor activity in vitro. It has less cardiac toxicity than the anthracyclines.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Piroxantrone is an anthrapyrazole derivative with broad antitumor activity in vitro. " | ( Pharmacokinetics of piroxantrone in a phase I trial of piroxantrone and granulocyte-colony stimulating factor. Balis, FM; Berg, SL; Cowan, KH; Denicoff, AM; Hillig, M; O'Shaughnessy, JA; Poplack, DG; Savarese, DM, 1993) | 2.05 |
| "Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activity in vitro and less cardiac toxicity than the anthracyclines. " | ( Pharmacokinetics, cerebrospinal fluid penetration, and metabolism of piroxantrone in the rhesus monkey. Balis, FM; Berg, SL; Godwin, KS; Poplack, DG, 1993) | 1.96 |
| "Piroxantrone is an anthrapyrazole compound undergoing phase II testing in a variety of diseases. " | ( Phase II trial of piroxantrone for advanced or metastatic soft tissue sarcomas. A Southwest Oncology Group study. Balcerzak, SP; Belt, RJ; Benedetti, J; Goodwin, JW; Hantel, A; Hutchins, LF; Zalupski, MM, 1993) | 2.06 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "Piroxantrone has minimal activity against gastric adenocarcinoma and no further investigation of this agent on this schedule in this disease is recommended." | ( Phase II trial of piroxantrone in gastric carcinoma. A Southwest Oncology Group study. Gluck, WL; Hantel, A; Macdonald, JS; Tangen, C, 1994) | 1.34 |
Piroxantrone was studied in plasma and cerebrospinal fluid in a non-human primate model. A 1-h infusion of the drug in combination with granulocyte-colony stimulating factor was conducted.
| Excerpt | Relevance | Reference |
|---|---|---|
| " The combined formulation and statistical optimization strategy provide a basis to develop other microparticulate systems and led to a dosage form that can be used for future in vivo investigations." | ( Optimized formulation of magnetic chitosan microspheres containing the anticancer agent, oxantrazole. Gallo, JM; Hassan, EE; Parish, RC, 1992) | 0.28 |
| " Thirty-seven patients were studied over a dosage range of 150 to 555 mg/m2." | ( Pharmacokinetics of piroxantrone in a phase I trial of piroxantrone and granulocyte-colony stimulating factor. Balis, FM; Berg, SL; Cowan, KH; Denicoff, AM; Hillig, M; O'Shaughnessy, JA; Poplack, DG; Savarese, DM, 1993) | 0.61 |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| DNA topoisomerase 2-alpha | Homo sapiens (human) | IC50 (µMol) | 4.6000 | 0.4800 | 4.3564 | 9.9400 | AID381809 |
| Integrase | Human immunodeficiency virus 1 | IC50 (µMol) | 13.5000 | 0.0005 | 1.5443 | 10.0000 | AID261420; AID261421 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1079949 | Proposed mechanism(s) of liver damage. [column 'MEC' 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] | |||
| AID381808 | Resistance factor, ratio of IC50 for etoposide-resistant human K/VP.5 cells to IC50 for human K562 cells | 2008 | Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7 | The structure-based design, synthesis and biological evaluation of DNA-binding bisintercalating bisanthrapyrazole anticancer compounds. |
| 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] | |||
| AID1079946 | Presence of at least one case with successful reintroduction. [column 'REINT' in source] | |||
| 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 | |||
| AID1079932 | Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source] | |||
| AID381806 | Growth inhibition of human K562 cells after 72 hrs by MTS method | 2008 | Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7 | The structure-based design, synthesis and biological evaluation of DNA-binding bisintercalating bisanthrapyrazole anticancer compounds. |
| AID261421 | Inhibition of strand transfer activity of HIV1 integrase | 2006 | Journal of medicinal chemistry, Mar-09, Volume: 49, Issue:5 | Dynamic pharmacophore model optimization: identification of novel HIV-1 integrase 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] | |||
| AID261420 | Inhibition of 3'-processing activity of HIV1 integrase | 2006 | Journal of medicinal chemistry, Mar-09, Volume: 49, Issue:5 | Dynamic pharmacophore model optimization: identification of novel HIV-1 integrase inhibitors. |
| AID1079945 | Animal toxicity known. [column 'TOXIC' in source] | |||
| AID1079940 | Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source] | |||
| AID1079944 | Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source] | |||
| AID1079942 | Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source] | |||
| AID1079939 | Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source] | |||
| AID381807 | Growth inhibition of etoposide-resistant human K/VP.5 cells after 72 hrs by MTS method | 2008 | Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7 | The structure-based design, synthesis and biological evaluation of DNA-binding bisintercalating bisanthrapyrazole anticancer compounds. |
| 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] | |||
| AID1079948 | Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source] | |||
| 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] | |||
| AID381805 | Binding affinity to calf thymus DNA assessed as change in thermal stability at 2 uM in tris-HCl buffer at pH 7.5 by thermal denaturation assay | 2008 | Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7 | The structure-based design, synthesis and biological evaluation of DNA-binding bisintercalating bisanthrapyrazole anticancer compounds. |
| AID381809 | Inhibition of human topoisomerase 2alpha decantation activity | 2008 | Bioorganic & medicinal chemistry, Apr-01, Volume: 16, Issue:7 | The structure-based design, synthesis and biological evaluation of DNA-binding bisintercalating bisanthrapyrazole anticancer compounds. |
| 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] | |||
| AID1079943 | Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source] | |||
| AID1159607 | Screen for inhibitors of RMI FANCM (MM2) intereaction | 2016 | Journal of biomolecular screening, Jul, Volume: 21, Issue:6 | A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 5 (12.82) | 18.7374 |
| 1990's | 29 (74.36) | 18.2507 |
| 2000's | 2 (5.13) | 29.6817 |
| 2010's | 1 (2.56) | 24.3611 |
| 2020's | 2 (5.13) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
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 (16.36) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 18 (41.86%) | 5.53% |
| Reviews | 3 (6.98%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 22 (51.16%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||