Page last updated: 2024-12-06

pentamethylmelamine

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

Description

Pentamethylmelamine (PMM) is a highly symmetric, stable, and crystalline organic compound with a triazine core structure. It is a potent inhibitor of DNA synthesis and has been investigated for its potential as an anticancer agent. PMM can be synthesized via a multi-step process involving the reaction of melamine with formaldehyde followed by methylation using various reagents like dimethyl sulfate. PMM exhibits a wide range of biological effects, including anti-proliferative activity against various cancer cell lines, induction of apoptosis, and inhibition of tumor growth in animal models. Its anticancer mechanism is believed to involve the disruption of DNA replication and repair processes. Furthermore, PMM has been explored for its potential applications in other areas, such as flame retardants, and polymer synthesis. The study of PMM is driven by its unique chemical structure, its potent biological activities, and its potential to be developed into a novel therapeutic agent for the treatment of various cancers.'

pentamethylmelamine: RN given refers to parent cpd [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID27775
CHEMBL ID457723
SCHEMBL ID38832
MeSH IDM0077655

Synonyms (49)

Synonym
smr000114173
n-[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-n-methylamine
MLS000548114 ,
NCIMECH_000088
NCI60_018874
brn 0747238
melamine, pentamethyl-
n,n,n',n''-pentamethyl-1,3,5-triazine-2,4,6-triamine
1,3,5-triazine-2,4,5-triamine, n,n,n',n',n''-pentamethyl-
pentamethylmelamine
unt 51239
n,n,n',n',n''-pentamethyl-1,3,5-triazine-2,4,6-triamine
1,3,5-triazine-2,4,6-triamine, n,n,n',n''-pentamethyl-
n,n,n',n',n''-pentamethyl-1,3,5-triazine
ai3-51239
nsc654383
nsc-654383
n2,n2,n4,n4,n6-pentamethyl-1,3,5-triazine-2,4,6-triamine
pmm hcl
melamine, n2,n2,n4,n4,n6-pentamethyl-
1,3,5-triazine-2,4,6-triamine, n,n,n',n', n''-pentamethyl-
1,3,5-triazine-2,4,6-triamine, n,n,n',n', n''-pentamethyl-, monohydrochloride
pentamethylmelamine-
melamine, n2,n2,n4,n4,n6-pentamethyl-, monohydrochloride
n~2~,n~2~,n~4~,n~4~,n~6~-pentamethyl-1,3,5-triazine-2,4,6-triamine
NCI60_000447
pentamethyl melamine
CHEMBL457723
2-n,2-n,4-n,4-n,6-n-pentamethyl-1,3,5-triazine-2,4,6-triamine
NCGC00247185-01
16268-62-5
AKOS006272558
uef6r96k8r ,
unii-uef6r96k8r
HMS2235H03
CCG-35281
HMS3371F09
SCHEMBL38832
[4-(dimethylamino)-6-(methylamino)-s-triazin-2-yl]-dimethyl-amine
cid_27775
bdbm89840
unt-51239
1,3,5-triazine-2,4,6-triamine, n2,n4,n4,n6,n6-pentamethyl-
1,3,5-triazine-2,4,6-triamine, n,n,n',n',n''-pentamethyl-
XIFVTSIIYVGRHJ-UHFFFAOYSA-N
OPERA_ID_195
DTXSID80167428
2-n,2-n,4-n,6-n,6-n-pentamethyl-1,3,5-triazine-2,4,6-triamine
Q27291043

Research Excerpts

Overview

Pentamethylmelamine (PMM) is a water-soluble monodemethylated derivative of hexamethylMelamine. PMM has a similar spectrum of activity against murine tumors.

ExcerptReferenceRelevance
"Pentamethylmelamine is a soluble monodemethylated derivative of hexamethylmelamine. "( Phase I study of pentamethylmelamine.
Goldberg, RS; Griffin, JP; Krakoff, IH; McSherry, JW, 1980
)
2.04
"Pentamethylmelamine (PMM) is a water-soluble monodemethylated derivative of hexamethylmelamine and has a similar spectrum of activity against murine tumors. "( Phase I trial of pentamethylmelamine: a clinical and pharmacologic study.
Barlock, AL; Boyd, MR; Cordes, RS; Dutcher, JS; Hubbard, SM; Ihde, DC; Jones, RB; Young, RC,
)
1.91

Toxicity

ExcerptReferenceRelevance
"Hexamethylmelamine (HMM) and a number of its derivatives are toxic to PC6 plasmacytoma cells in vitro."( In vitro cytotoxicity of the methylmelamines.
Abel, G; Rutty, CJ, 1980
)
0.26

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic studies in mouse, rat and man did not show the major species differences characteristic of PMM."( Preclinical toxicology, pharmacokinetics and formulation of N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine (trimelamol), a water-soluble cytotoxic s-triazine which does not require metabolic activation.
Abel, G; Goddard, PM; Harrap, KR; Judson, IR; Newell, DR; Rutty, CJ, 1986
)
0.27
" Pharmacokinetic data were analyzed by an original method using a nonlinear cost function minimized by a simplex algorithm."( Pharmacokinetics and metabolism of hexamethylmelamine in mice after IP administration.
Abikhalil, F; Atassi, G; Dubois, J; Hanocq, M, 1986
)
0.27
" HMM, PMM, and 2,2,4,6 TetrMM concentrations determined in RC tissues were much higher than the plasma values, as indicated by the pharmacokinetic parameters (Cmax and AUC)."( Pharmacokinetics and metabolism of hexamethylmelamine in mice bearing renal cell tumors.
Abikhalil, F; Atassi, G; Dubois, J; Hanocq, M, 1988
)
0.27
" Pharmacokinetic studies (100-500 mg m-2) indicated that PMM plasma levels are dose-dependent and that the PMM disposition-phase half-life is prolonged in patients with abnormal liver function."( Pentamethylmelamine (PMM): Phase I clinical and pharmacokinetic studies.
Harrap, KR; Muindi, JR; Newell, DR; Smith, IE, 1983
)
1.71
" The half-life of HMM was 44."( Pharmacokinetics of hexamethylmelamine and pentamethylmelamine in mice.
Broggini, M; Colombo, T; D'Incalci, M; Donnelli, MG; Garattini, S; Gescher, A,
)
0.39
" In view of the highly cytotoxic nature of N-methylolmelamines, we conclude that these pharmacokinetic differences may be related to the antitumour effectiveness of PMM in mouse, rat, and man."( The comparative pharmacokinetics of pentamethylmelamine in man, rat, and mouse.
Harrap, KR; Muindi, JR; Newell, DR; Rutty, CJ, 1982
)
0.54

Bioavailability

ExcerptReferenceRelevance
" The reduced bioavailability of HMM intraduodenally was thus a consequence of presystemic elimination in the liver and the gut wall."( Low oral bioavailability of hexamethylmelamine in the rat due to simultaneous hepatic and intestinal metabolism.
Hofman, G; Hulshoff, A; Klippert, PJ; Mingels, MJ; Noordhoek, J, 1983
)
0.27

Dosage Studied

ExcerptRelevanceReference
" Further phase I studies, with different PMM dosage schedules, are necessary before phase II studies can be recommended."( Hexamethylmelamine and pentamethylmelamine: an update.
Hahn, DA, 1983
)
0.58
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (8)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, JmjC domain-containing histone demethylation protein 3AHomo sapiens (human)Potency35.48130.631035.7641100.0000AID504339
TDP1 proteinHomo sapiens (human)Potency22.14270.000811.382244.6684AID686978; AID686979
regulator of G-protein signaling 4Homo sapiens (human)Potency79.43280.531815.435837.6858AID504845
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency89.12510.354828.065989.1251AID504847
peptidyl-prolyl cis-trans isomerase NIMA-interacting 1Homo sapiens (human)Potency50.11870.425612.059128.1838AID504891
gemininHomo sapiens (human)Potency0.00460.004611.374133.4983AID624296
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
corticotropin-releasing hormone receptor 2Homo sapiens (human)EC50 (µMol)53.00001.120011.561736.8000AID602473
corticotropin releasing factor-binding proteinHomo sapiens (human)EC50 (µMol)53.00001.120011.561736.8000AID602473
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (43)

Assay IDTitleYearJournalArticle
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID409954Inhibition of mouse 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.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1079938Chronic 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]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079935Cytolytic 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]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079933Acute 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
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1079931Moderate 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]
AID1079936Choleostatic 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]
AID1224864HCS microscopy assay (F508del-CFTR)2016PloS one, , Volume: 11, Issue:10
Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (45)

TimeframeStudies, This Drug (%)All Drugs %
pre-199038 (84.44)18.7374
1990's0 (0.00)18.2507
2000's2 (4.44)29.6817
2010's4 (8.89)24.3611
2020's1 (2.22)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.00

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 weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index10.00 (24.57)
Research Supply Index4.04 (2.92)
Research Growth Index4.04 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.00)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (9.80%)5.53%
Reviews2 (3.92%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other44 (86.27%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]