Page last updated: 2024-12-05

porfiromycin

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Porfiromycin is an alkylating agent that inhibits DNA synthesis by forming covalent bonds with the N7 position of guanine bases in DNA. It was originally synthesized in the 1960s as a potential anticancer drug, but its clinical use was limited due to its severe toxicity. Despite this, porfiromycin has continued to be studied for its potential therapeutic applications. Notably, it has demonstrated activity against various types of cancer, including leukemia, lymphoma, and solid tumors. Research into porfiromycin's mechanism of action has revealed its ability to induce DNA damage, leading to cell cycle arrest and apoptosis. It also exhibits anti-angiogenic properties, inhibiting the formation of new blood vessels that tumors require for growth. More recent studies have explored the use of porfiromycin in combination with other therapies, such as radiation or immunotherapy, to enhance its effectiveness and reduce its side effects. The unique properties of porfiromycin, including its potent anti-tumor activity and its ability to overcome drug resistance, make it a valuable tool in the development of new cancer therapies. Despite its toxicity, porfiromycin continues to be a subject of ongoing research due to its potential to address unmet medical needs in cancer treatment.'
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Porfiromycin: Toxic antibiotic of the mitomycin group, obtained from MITOMYCIN and also from Streptomyces ardus and other species. It is proposed as an antineoplastic agent, with some antibiotic properties. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID13116
CHEMBL ID521078
SCHEMBL ID5046
MeSH IDM0017329

Synonyms (42)

Synonym
nsc-56410
n-methylmitomycin c
porfiromycin
6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-1,5-dimethyl-azirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione, carbamate ester
801-52-5
(amino-methoxy-dimethyl-dioxo-[?]yl)methyl carbamate
D05572
porfiromycin (usan/inn)
6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-1,5-dimethylazirino(2',3':3,4)pyrrolo(1,2-a)indole-4,7-dione carbamate (ester)
u-14743
porfiromycine [inn-french]
porfiromycin [usan:inn:ban]
azirino(2',3':3,4)pyrrolo(1,2-a)indole-4,7-dione, 6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a- methoxy-1,5-dimethyl-, carbamate (ester)
ai3-50825
azirino(2',3':3,4)pyrrolo(1,2-a)-indole-4,7-dione, 6-amino-8-(((aminocarbonyl)oxy)methyl)-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-1,5-dimethyl-
porfiromicina [inn-spanish]
porfiromycinum [inn-latin]
azirino(2',3':3,4)pyrrolo(1,2-a)indole-4,7-dione, 6-amino-8-(((aminocarbonyl)oxy)methyl)-1,1a,2,8,8a,8b- hexahydro-8a-methoxy-1,5-dimethyl-,(1ar-(1aalpha,8beta,8aalpha,8balpha))-
azirino(2',3':3,4)pyrrolo(1,2-a)indole-4,7-dione, 6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-1,5-dimethyl-, carbamate (ester)
CHEMBL521078
u-14,743
porfiromycinum
h1wk901oa6 ,
porfiromicina
unii-h1wk901oa6
azirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione,6-amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-1,5-dimethyl-,(1as,8s,8ar,8bs)-
SCHEMBL5046
porfiromycin [mart.]
porfiromycin [mi]
porfiromycin [who-dd]
(1as-(1a.alpha.,8.beta.,8a.alpha.,8b.alpha.))-6-amino-8-(((aminocarbonyl)oxy)methyl)-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-1,5-dimethylazirino(2';,3';:3,4)pyrrolo(1,2-a)indole-4,7-dione
porfiromycin [usan]
porfiromycin [inn]
n-methylmitomycin c [mi]
((1as,8s,8ar,8bs)-6-amino-8a-methoxy-1,5-dimethyl-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2',3':3,4]pyrrolo[1,2-a]indol-8-yl)methyl carbamate
DB06478
Q27279527
[(4s,6s,7r,8s)-11-amino-7-methoxy-5,12-dimethyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
DTXSID901024646
CS-0007759
HY-13730
azirino[2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione, 6-amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-1,5-dimethyl-, (1as,8s,8ar,8bs)-

Research Excerpts

Overview

Porfiromycin (PM) is an analog to MMC that generates oxygen radicals at a significantly lower level than the parent compound.

ExcerptReferenceRelevance
"Porfiromycin (PM) is an analog to MMC that generates oxygen radicals at a significantly lower level than the parent compound."( Inhibition of mitomycin C's aerobic toxicity by the seleno-organic antioxidant PZ-51.
Gustafson, DL; Pritsos, CA, 1991
)
1

Effects

ExcerptReferenceRelevance
"porfiromycin, there have been no statistically significant differences between the two arms with respect to white blood cell count (WBC), platelet, or hemoglobin nadirs."( Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck.
Fischer, D; Fischer, JJ; Haffty, BG; Papac, R; Rockwell, S; Ross, D; Sartorelli, AC; Sasaki, CT; Son, YH; Wilson, LD, 1997
)
1.31

Toxicity

Mitomycin C (MC) and its structural analogs porfiromycin (PM), BMY-25282 and BL-6783 are toxic to EMT6 cells under aerobic and hypoxic conditions. DIC sensitizes cells to two MC analogues in hypoxia and protects cells from these agents in air, despite the fact that POR is preferentially toxic to hypoxic cells.

ExcerptReferenceRelevance
" We now demonstrate that DIC sensitizes EMT6 cells to two MC analogues, porfiromycin (POR) and the 7-N-dimethylaminomethylene analogue of mitomycin C (BMY-25282), in hypoxia and protects cells from these agents in air, despite the fact that POR is preferentially toxic to hypoxic cells and BMY-25282 is preferentially toxic to aerobic cells."( Modification of the metabolism and cytotoxicity of bioreductive alkylating agents by dicoumarol in aerobic and hypoxic murine tumor cells.
Keyes, SR; Rockwell, S; Sartorelli, AC, 1989
)
0.51
" In vitro, POR was more toxic to hypoxic EMT6 cells than to aerobic cells."( Modulation of the cytotoxicity of porfiromycin by dicoumarol in vitro and in vivo.
Keyes, SR; Rockwell, S; Sartorelli, AC,
)
0.41
"Mitomycin C (MC) and its structural analogs porfiromycin (PM), BMY-25282 and BL-6783 are toxic to EMT6 cells under aerobic and hypoxic conditions."( Effect of the superoxide dismutase inhibitor, diethyldithiocarbamate, on the cytotoxicity of mitomycin antibiotics.
Keyes, SR; Pritsos, CA; Sartorelli, AC, 1989
)
0.54
" Agents which are preferentially toxic to cells with low oxygen contents could therefore be useful as adjuncts to the regimens now used to treat these cancers."( Porfiromycin as a bioreductive alkylating agent with selective toxicity to hypoxic EMT6 tumor cells in vivo and in vitro.
Keyes, SR; Rockwell, S; Sartorelli, AC, 1985
)
1.71

Compound-Compound Interactions

ExcerptReferenceRelevance
"Porfiromycin (methyl mitomycin C) has been shown in laboratory studies to have increased preferential cytotoxicity to hypoxic cells and therefore may provide enhanced therapeutic efficacy over mitomycin C when used in combination with radiation therapy (RT)."( Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck.
Fischer, D; Fischer, JJ; Haffty, BG; Papac, R; Rockwell, S; Ross, D; Sartorelli, AC; Sasaki, CT; Son, YH; Wilson, LD, 1997
)
2.03

Dosage Studied

ExcerptRelevanceReference
" In contrast, treatment of solid EMT6 tumors in vivo with POR plus radiation produced supra-additive cytotoxicity, as assessed by analyses of the complete dose-response curves for the killing of tumor cells by radiation alone or by POR alone."( Preclinical studies of porfiromycin as an adjunct to radiotherapy.
Keyes, SR; Rockwell, S; Sartorelli, AC, 1988
)
0.59
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (16)

Assay IDTitleYearJournalArticle
AID134403Anti cancer activity was determined as lethal dose1993Journal of medicinal chemistry, May-14, Volume: 36, Issue:10
Structure-activity relationships for mitomycins. Application of the distance and charge analysis method.
AID124097in vivo activity against aerobic and hypoxic cells in RIF-1 tumors when administered at a dose of 225 umol/kg in mice2001Journal of medicinal chemistry, Oct-11, Volume: 44, Issue:21
Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine.
AID115627Minimum effective dose that show activity against P-388 murine leukemia cells in CDF1 female mice, after intraperitoneal administration (optimal dose is 12.8 mg/kg)1981Journal of medicinal chemistry, Aug, Volume: 24, Issue:8
Development of new mitomycin C and porfiromycin analogues.
AID120904T/C value was measured as tumor volume in the treated versus control mice.1995Journal of medicinal chemistry, Aug-04, Volume: 38, Issue:16
Synthesis and antitumor activity of various 6-demethylmitomycins and 6-demethyl-6-halomitomycins.
AID235400Therapeutic ratio is expressed as ratio of optimal dose and minimum effective dose1981Journal of medicinal chemistry, Aug, Volume: 24, Issue:8
Development of new mitomycin C and porfiromycin analogues.
AID121918Antitumor activity against P-388 murine leukemia cells in CDF1 female mice after intraperitoneal administration at the specified optimal dose of 12.8 mg/kg1981Journal of medicinal chemistry, Aug, Volume: 24, Issue:8
Development of new mitomycin C and porfiromycin analogues.
AID128822Anti cancer activity was determined as effective dose1993Journal of medicinal chemistry, May-14, Volume: 36, Issue:10
Structure-activity relationships for mitomycins. Application of the distance and charge analysis method.
AID124099in vivo activity against aerobic and hypoxic cells in RIF-1 tumors when administered at a dose of 225 umol/kg in mice after 5 min of exposure to radiation2001Journal of medicinal chemistry, Oct-11, Volume: 44, Issue:21
Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine.
AID11333350% inhibition of solid tumor growth (Sarcoma 180 cells) in mice1995Journal of medicinal chemistry, Aug-04, Volume: 38, Issue:16
Synthesis and antitumor activity of various 6-demethylmitomycins and 6-demethyl-6-halomitomycins.
AID119966Optimal dose was measured against sarcoma 180 cell in mice1995Journal of medicinal chemistry, Aug-04, Volume: 38, Issue:16
Synthesis and antitumor activity of various 6-demethylmitomycins and 6-demethyl-6-halomitomycins.
AID432751Antitumor activity against mouse S180 cells implanted in ip dosed ddY mouse assessed as tumor volume after 7 days2009European journal of medicinal chemistry, Sep, Volume: 44, Issue:9
Aziridine alkaloids as potential therapeutic agents.
AID124098in vivo activity against aerobic and hypoxic cells in RIF-1 tumors when administered at a dose of 225 umol/kg in mice 30 min before exposure to radiation2001Journal of medicinal chemistry, Oct-11, Volume: 44, Issue:21
Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine.
AID227069Inhibition of HeLa S3 cell growth relative to mitomycin C action (ratio of IC50 values)1995Journal of medicinal chemistry, Aug-04, Volume: 38, Issue:16
Synthesis and antitumor activity of various 6-demethylmitomycins and 6-demethyl-6-halomitomycins.
AID409958Inhibition of bovine brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID115134In vivo toxicity against C3H/HeN cell line in mice expressed as maximal tolerated dose2001Journal of medicinal chemistry, Oct-11, Volume: 44, Issue:21
Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine.
AID432750Toxicity in ip dosed ddY mouse bearing mouse S180 cells2009European journal of medicinal chemistry, Sep, Volume: 44, Issue:9
Aziridine alkaloids as potential therapeutic agents.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (81)

TimeframeStudies, This Drug (%)All Drugs %
pre-199042 (51.85)18.7374
1990's31 (38.27)18.2507
2000's8 (9.88)29.6817
2010's0 (0.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.85

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.

MetricThis Compound (vs All)
Research Demand Index18.85 (24.57)
Research Supply Index4.57 (2.92)
Research Growth Index4.13 (4.65)
Search Engine Demand Index18.60 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.85)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (5.49%)5.53%
Reviews6 (6.59%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other80 (87.91%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase III, Double-Blind, Randomized, Placebo-Controlled Study of Porfiromycin Used as an Adjuvant to Radiation Therapy in Postoperative Head and Neck Cancer Patients [NCT02183246]Phase 33 participants (Actual)Interventional2000-05-31Terminated
A Phase I Intensive Pharmacokinetic Study of Porfiromycin in Head and Neck Cancer and Other Cancer Patients With Solid Tumors Who Receive Radiation Therapy [NCT02209701]Phase 13 participants (Actual)Interventional1999-12-31Terminated
A Phase III Double-Blind, Randomised, Placebo-Controlled Study of Porfiromycin When Used as an Adjuvant to Radiation Therapy in Patients With Head and Neck Cancer [NCT00003328]Phase 3600 participants (Anticipated)Interventional1997-12-31Completed
RADIATION WITH MITOMYCIN C OR PORFIROMYCIN IN THE TREATMENT OF CANCER OF THE HEAD AND NECK AREA [NCT00002507]Phase 30 participants Interventional1992-11-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]