Page last updated: 2024-12-07

hepsulfam

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

Description

hepsulfam: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID100606
CHEMBL ID182440
SCHEMBL ID5409150
MeSH IDM0148973

Synonyms (31)

Synonym
NCI60_002882
hepsulfam
1,7-heptanediol disulfamate
nsc-329680
96892-57-8
sulfamic acid,7-heptanediyl ester
nsc329680
sulfamic acid, 1,7-heptanediyl ester
7-sulfamoyloxyheptyl sulfamate
sulfamic acid 7-sulfamoyloxy-heptyl ester
nsc 329680
sulfamic acid 1,7-heptanediyl ester
bdbm50154471
CHEMBL182440 ,
unii-971du2gq51
971du2gq51 ,
SCHEMBL5409150
DTXSID90242619
nci-329680
sulfamic acid, s,s'-1,7-heptanediyl ester
1,7-heptanediyl sulfamate
HY-U00095
CS-7131
1,7-heptanediol bissulfamate
nci 329680;zinc01574758
heptane-1,7-diyl bis(sulfamate)
zinc01574758
nci 329680
MS-24144
7-(sulfamoyloxy)heptyl sulfamate
AKOS040741833

Research Excerpts

Overview

Hepsulfam is a bisulfamic ester which is similar in structure to busulfan. It is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks.

ExcerptReferenceRelevance
"Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. "( Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies.
Geller, RB; Grochow, LB; Janisch, L; Larson, RA; Milton, J; Ratain, MJ, 1995
)
1.98

Effects

ExcerptReferenceRelevance
"Hepsulfam has shown broad antineoplastic activity in preclinical studies."( A phase I clinical and pharmacokinetic trial of hepsulfam.
Brown, TD; Havlin, KA; Koeller, JM; Kuhn, JG; Marshall, MV; Ravdin, PM; Rodriguez, G; Von Hoff, DD, 1991
)
1.26

Toxicity

ExcerptReferenceRelevance
" Human BFU-e were greatly inhibited by PZDH, whereas murine BFU-e were relatively resistant to its toxic effects."( Comparative toxicity of fostriecin, hepsulfam and pyrazine diazohydroxide to human and murine hematopoietic progenitor cells in vitro.
Du, DL; Grieshaber, CK; Murphy, MJ; Volpe, DA, 1991
)
0.56
" We have recently shown that hepsulfam was more toxic to L1210 leukemia cells than was busulfan."( Mechanisms of toxicity of hepsulfam in human tumor cell lines.
Cook, C; Gibson, NW; Hincks, JR; Pacheco, DY, 1990
)
0.87
" Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy."( Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies.
Geller, RB; Grochow, LB; Janisch, L; Larson, RA; Milton, J; Ratain, MJ, 1995
)
0.53

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic studies revealed that the clearance rate of hepsulfam is linear over the dose range studied and that its plasma disposition is biphasic with mean alpha and beta half-lives of 19 +/- 18 (SE) min and 337 +/- 248 (SE) min, respectively."( Phase I and pharmacokinetic study of hepsulfam (NSC 329680).
Donehower, RC; Ettinger, DS; Forastiere, AA; Grochow, LB; Hendricks, CB; Lubejko, B; McGuire, WP; Rowinsky, EK; Sartorius, S, 1991
)
0.8
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Carbonic anhydrase 1Homo sapiens (human)Ki0.14500.00001.372610.0000AID238620
Carbonic anhydrase 2Homo sapiens (human)Ki0.00800.00000.72369.9200AID238635
Cytochrome P450 2D6Homo sapiens (human)IC50 (µMol)699.00000.00002.015110.0000AID240619
Carbonic anhydrase 9Homo sapiens (human)Ki0.01010.00010.78749.9000AID239048
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (31)

Processvia Protein(s)Taxonomy
one-carbon metabolic processCarbonic anhydrase 1Homo sapiens (human)
morphogenesis of an epitheliumCarbonic anhydrase 2Homo sapiens (human)
positive regulation of synaptic transmission, GABAergicCarbonic anhydrase 2Homo sapiens (human)
positive regulation of cellular pH reductionCarbonic anhydrase 2Homo sapiens (human)
angiotensin-activated signaling pathwayCarbonic anhydrase 2Homo sapiens (human)
regulation of monoatomic anion transportCarbonic anhydrase 2Homo sapiens (human)
secretionCarbonic anhydrase 2Homo sapiens (human)
regulation of intracellular pHCarbonic anhydrase 2Homo sapiens (human)
neuron cellular homeostasisCarbonic anhydrase 2Homo sapiens (human)
positive regulation of dipeptide transmembrane transportCarbonic anhydrase 2Homo sapiens (human)
regulation of chloride transportCarbonic anhydrase 2Homo sapiens (human)
carbon dioxide transportCarbonic anhydrase 2Homo sapiens (human)
one-carbon metabolic processCarbonic anhydrase 2Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 2D6Homo sapiens (human)
steroid metabolic processCytochrome P450 2D6Homo sapiens (human)
cholesterol metabolic processCytochrome P450 2D6Homo sapiens (human)
estrogen metabolic processCytochrome P450 2D6Homo sapiens (human)
coumarin metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid catabolic processCytochrome P450 2D6Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 2D6Homo sapiens (human)
isoquinoline alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2D6Homo sapiens (human)
retinol metabolic processCytochrome P450 2D6Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 2D6Homo sapiens (human)
negative regulation of bindingCytochrome P450 2D6Homo sapiens (human)
oxidative demethylationCytochrome P450 2D6Homo sapiens (human)
negative regulation of cellular organofluorine metabolic processCytochrome P450 2D6Homo sapiens (human)
arachidonic acid metabolic processCytochrome P450 2D6Homo sapiens (human)
response to hypoxiaCarbonic anhydrase 9Homo sapiens (human)
morphogenesis of an epitheliumCarbonic anhydrase 9Homo sapiens (human)
response to xenobiotic stimulusCarbonic anhydrase 9Homo sapiens (human)
response to testosteroneCarbonic anhydrase 9Homo sapiens (human)
secretionCarbonic anhydrase 9Homo sapiens (human)
one-carbon metabolic processCarbonic anhydrase 9Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (15)

Processvia Protein(s)Taxonomy
arylesterase activityCarbonic anhydrase 1Homo sapiens (human)
carbonate dehydratase activityCarbonic anhydrase 1Homo sapiens (human)
protein bindingCarbonic anhydrase 1Homo sapiens (human)
zinc ion bindingCarbonic anhydrase 1Homo sapiens (human)
hydro-lyase activityCarbonic anhydrase 1Homo sapiens (human)
cyanamide hydratase activityCarbonic anhydrase 1Homo sapiens (human)
arylesterase activityCarbonic anhydrase 2Homo sapiens (human)
carbonate dehydratase activityCarbonic anhydrase 2Homo sapiens (human)
protein bindingCarbonic anhydrase 2Homo sapiens (human)
zinc ion bindingCarbonic anhydrase 2Homo sapiens (human)
cyanamide hydratase activityCarbonic anhydrase 2Homo sapiens (human)
monooxygenase activityCytochrome P450 2D6Homo sapiens (human)
iron ion bindingCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activityCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 2D6Homo sapiens (human)
heme bindingCytochrome P450 2D6Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
carbonate dehydratase activityCarbonic anhydrase 9Homo sapiens (human)
protein bindingCarbonic anhydrase 9Homo sapiens (human)
zinc ion bindingCarbonic anhydrase 9Homo sapiens (human)
molecular function activator activityCarbonic anhydrase 9Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (14)

Processvia Protein(s)Taxonomy
cytosolCarbonic anhydrase 1Homo sapiens (human)
extracellular exosomeCarbonic anhydrase 1Homo sapiens (human)
cytoplasmCarbonic anhydrase 2Homo sapiens (human)
cytosolCarbonic anhydrase 2Homo sapiens (human)
plasma membraneCarbonic anhydrase 2Homo sapiens (human)
myelin sheathCarbonic anhydrase 2Homo sapiens (human)
apical part of cellCarbonic anhydrase 2Homo sapiens (human)
extracellular exosomeCarbonic anhydrase 2Homo sapiens (human)
cytoplasmCarbonic anhydrase 2Homo sapiens (human)
plasma membraneCarbonic anhydrase 2Homo sapiens (human)
apical part of cellCarbonic anhydrase 2Homo sapiens (human)
mitochondrionCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulumCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2D6Homo sapiens (human)
cytoplasmCytochrome P450 2D6Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2D6Homo sapiens (human)
nucleolusCarbonic anhydrase 9Homo sapiens (human)
plasma membraneCarbonic anhydrase 9Homo sapiens (human)
membraneCarbonic anhydrase 9Homo sapiens (human)
basolateral plasma membraneCarbonic anhydrase 9Homo sapiens (human)
microvillus membraneCarbonic anhydrase 9Homo sapiens (human)
plasma membraneCarbonic anhydrase 9Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (24)

Assay IDTitleYearJournalArticle
AID238620Inhibitory activity against cytosolic human carbonic anhydrase I2005Bioorganic & medicinal chemistry letters, Feb-01, Volume: 15, Issue:3
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with bis-sulfamates.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' 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]
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]
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' 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]
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID240619Inhibitory concentration against cytochrome P450 2D62004Journal of medicinal chemistry, Oct-21, Volume: 47, Issue:22
Validation of model of cytochrome P450 2D6: an in silico tool for predicting metabolism and inhibition.
AID243098Ratio of inhibitory activity of human cytosolic carbonic anhydrase II to tumor associated carbonic anhydrase IX2005Bioorganic & medicinal chemistry letters, Feb-01, Volume: 15, Issue:3
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with bis-sulfamates.
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]
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]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' 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]
AID239048Inhibitory activity against membrane bound tumor associated human carbonic anhydrase IX2005Bioorganic & medicinal chemistry letters, Feb-01, Volume: 15, Issue:3
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with bis-sulfamates.
AID238635Inhibitory activity against cytosolic human carbonic anhydrase II2005Bioorganic & medicinal chemistry letters, Feb-01, Volume: 15, Issue:3
Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with bis-sulfamates.
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
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (22)

TimeframeStudies, This Drug (%)All Drugs %
pre-19904 (18.18)18.7374
1990's15 (68.18)18.2507
2000's2 (9.09)29.6817
2010's1 (4.55)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (13.04%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other20 (86.96%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]