Page last updated: 2024-11-11

mitoguazone

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Description

Mitoguazone: Antineoplastic agent effective against myelogenous leukemia in experimental animals. Also acts as an inhibitor of animal S-adenosylmethionine decarboxylase. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

mitoguazone : A hydrazone obtained by formal condensation of the two carbonyl groups of methylglyoxal with the primary amino groups of two molecules of aminoguanidine. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID5351154
CHEMBL ID216913
CHEBI ID43996
SCHEMBL ID8454
SCHEMBL ID1736452
SCHEMBL ID11892956
MeSH IDM0013946

Synonyms (68)

Synonym
n''''-{2-[(diaminomethylene)hydrazono]-1-methylethylidene}carbonohydrazonic diamide
(2e)-2-((2e)-2-{[(z)-amino(imino)methyl]hydrazono}-1-methylethylidene)hydrazinecarboximidamide
methylglyoxalbisguanylhydrazone
bdbm50046201
(2e)-2-((2e)-2-{[(e)-amino(imino)methyl]hydrazono}-1-methylethylidene)hydrazinecarboximidamide
pa-001
zyrkamine
win-10708-2
methyl-gag
methyl-g
nsc-32946
methylglyoxal bis(amidinohydrazone)
pyruvaldehyde bis(amidinohydrazone)
me-gag
mitoguazone (inn)
D07258
NSC32946 ,
mitoguazone
(2e,2'e)-2,2'-(1e,2e)-propane-1,2-diylidenedihydrazinecarboximidamide
methylglyoxal bis(guanylhydrazone)
mggh
459-86-9
guanylhydrazone
1-[(e)-[(2e)-2-(carbamimidoylhydrazono)-1-methyl-ethylidene]amino]guanidine
nsc69432
guanidine, 1,1'-[(methylethanediylidene)dinitrilo]di-
methyl gag
mgbg
methylglyoxal bis-(guanylhydrazone)
methylglyoxalbis(guanylhydrazone)
CHEMBL216913 ,
chebi:43996 ,
2-[(e)-[(1e)-1-(diaminomethylidenehydrazinylidene)propan-2-ylidene]amino]guanidine
bdbm34068
nsc 69432 (mgbg)
od5q0l447w ,
mitoguazonum
mitoguazona
2,2'-(propane-1,2-diylidene)bis(hydrazinecarboximidamide)
A826951
AKOS006228668
nsc_9991
cas_9991
bdbm86163
CCG-35494
SCHEMBL8454
163955-22-4
1,1'-((methylethanediylidene)dinitrilo0diguanidine
mitoguazone [who-dd]
mitoguazone [mi]
2,2'-(1-methyl-1,2-ethanediylidene)bis(hydrazinecarboximidamide)
hydrazinecarboximidamide, 2,2'-(1-methyl-1,2-ethanediylidene)bis-, (e,e)-
mitoguazone [inn]
2,2'-(1-methyl-1,2-ethanediylidene)bis[hydrazinecarboximidamide]
SCHEMBL1736452
SCHEMBL11892956
AKOS025147464
STL490517
n'',n'''''-(1e,2e)-propane-1,2-diylidenedicarbonohydrazonic diamide
DB12967
(2e,2'e)-2,2'-(propane-1,2-diylidene)bis(hydrazine-1-carboximidamide)
MS-22987
CS-0026193
HY-106634
EN300-197516
n-{[1-(carbamimidamidoimino)propan-2-ylidene]amino}guanidine
Z2240938943
AKOS040754734

Research Excerpts

Overview

Mitoguazone is a known inhibitor of polyamine biosynthesis through competitive inhibition of S-adenosylmethionine decarboxylase. It is an effective agent in patients with multiply relapsed or refractory AIDS-related lymphoma.

ExcerptReferenceRelevance
"Mitoguazone is an antiproliferative agent used in chemotherapy. "( Rapid and sensitive quantitation of the antiproliferative agent mitoguazone in small volumes of plasma by high-performance liquid chromatography with ultraviolet detection.
Cheng, CL; Chou, CH; Lin, EG, 2003
)
2
"Mitoguazone is a known inhibitor of polyamine biosynthesis through competitive inhibition of S-adenosylmethionine decarboxylase. "( Effect of mitoguazone on polyamine oxidase activity in rat liver.
Berselli, D; Caimi, S; Ferioli, ME, 2004
)
2.17
"Mitoguazone is a unique chemotherapeutic agent whose activity is believed to result primarily from the competitive inhibition of S-adenosyl-methionine decarboxylase leading to a disruption in polyamine biosynthesis. "( Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma.
Kraynak, M; Kuhn, JG; Levine, AM; Mueck, R; Pearce, T; Rizzo, J; Smith, S; Von Hoff, DD; Weiss, GR, 1996
)
2.03
"Mitoguazone is an effective agent in patients with multiply relapsed or refractory AIDS-related lymphoma, with acceptable toxicity. "( Mitoguazone therapy in patients with refractory or relapsed AIDS-related lymphoma: results from a multicenter phase II trial.
Espina, B; Giles, F; Kaplan, L; Levine, AM; Luskey, BD; Northfelt, DW; Scadden, DT; Silverberg, I; Tessman, D; Tulpule, A; Von Hoff, D; Wernz, J, 1997
)
3.18
"Mitoguazone is a unique antitumor agent that interferes with polyamine synthesis that has been reported to have activity against AIDS-related malignant lymphoma. "( Evaluation of mitoguazone in patients with refractory chronic lymphocytic leukemia: a phase II study (P-H482) of the Eastern Cooperative Oncology Group.
Gordon, LI; Harris, JE; O'Connell, MJ; Oken, MM; Wiernik, PH, 1999
)
2.11

Effects

ExcerptReferenceRelevance
"Mitoguazone has also recently been documented to have activity in patients with AIDS-related lymphoma."( Mitoguazone induces apoptosis via a p53-independent mechanism.
Davidson, K; Izbicka, E; Koester, S; Petit, T; Von Hoff, DD, 1998
)
2.46

Toxicity

ExcerptReferenceRelevance
" The antioxidants glutathione, vitamin E and vitamin C reversed toxicity and antimitochondrial activity to a large extent implying that toxic free radical metabolites of the drug are of significance in cellular activity of MGBG."( Effect of antioxidants on the mitochondrial activity and toxicity of the cancer drug methylglyoxal bis (guanylhydrazone) in yeast and mammalian cells.
Cheng, LL; Collier, DC; Wilkie, D, 1990
)
0.28
" It proved to be toxic at 100 mg/kg body mass."( [Antineoplastic activity and toxicity of dihydroambazone in comparison with ambazone (1,4-benzoquinone-guanylhydrazone-thiosemicarbazone)].
Baumgart, J; Gutsche, W; Härtl, A; Schulze, W, 1990
)
0.28
" These results suggest that thrombocytopenia is the major dose-limiting side-effect of continuous DFMO infusion but does not occur at a dose of 500 mg/kg body wt/day."( Red blood cell polyamine levels and host toxicity during continuous alpha-difluoromethylornithine infusion.
Ajani, JA; Grossie, VB; Nishioka, K; Ota, DM; Stephens, LC, 1986
)
0.27
" Both drugs were judged too toxic to justify intrathecal or intraventricular studies with these agents in patients."( CNS toxicity and CSF pharmacokinetics of intraventricular DFMO and MGBG in beagle dogs.
Borcich, JK; Byrd, D; Campbell, J; Davis, RL; Levin, VA, 1984
)
0.27
"The toxicity to cultured cells of the cancer chemotherapeutic agent methylglyoxal-bis[guanylhydrazone] (MGBG) varies considerably between different cell lines and is always more toxic in the absence of exogenous polyamine."( Differential toxicity of methylglyoxal-bis [guanylhydrazone].
Dewey, DL; Gaugas, JM; Minchinton, AI; Stratford, MR, 1983
)
0.27
" Following an uncomplicated pregnancy, a healthy child was born at full term and careful haematological and immunological monitoring has revealed no adverse effects resulting from exposure to rituximab."( Safety of rituximab therapy during the first trimester of pregnancy: a case history.
Elinder, G; Kimby, E; Sverrisdottir, A, 2004
)
0.32

Pharmacokinetics

Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life. The method is suitable in pharmacokinetics investigation and monitoring mitoguAZone concentration.

ExcerptReferenceRelevance
" It could be shown that changes of the pharmacokinetic parameters as well as the distribution pattern of this drug were clearly influenced and dependent on the tumor stage but not by the tumor inoculation route."( Influence of melanoma B16 on the pharmacokinetics of mitoguazone in mice.
Amlacher, R; Baumgart, J; Bubner, M; Hoffmann, H; Horn, U; Mackowiak, A; Sühnel, J, 1991
)
0.53
" Therefore, if MGBG is administered by a frequent treatment schedule, the prolonged biological half-life in humans may significantly contribute to its clinical toxicity."( Pharmacokinetics of [14C]methylglyoxal-bis-guanylhydrazone) in patients with leukemia.
Keating, MJ; Loo, TL; Rosenblum, MG; Yap, BS, 1981
)
0.26
" Early pharmacokinetic studies of Mitoguazone in man revealed a prolonged half-life."( Pharmacokinetic profile of Mitoguazone (MGBG) in patients with AIDS related non-Hodgkin's lymphoma.
Kraynak, M; Kuhn, JG; Levine, AM; Mueck, R; Pearce, T; Rizzo, J; Smith, S; Von Hoff, DD; Weiss, GR, 1996
)
0.87
" In the present study, the pharmacodynamic effects at the cellular level of CHS 828 was compared to another compound containing two guanidino groups, methylglyoxal-bis(guanylhydrazone) (MGBG)."( Cellular pharmacodynamics of the cytotoxic guanidino-containing drug CHS 828. Comparison with methylglyoxal-bis(guanylhydrazone).
Binderup, L; Ekelund, S; Larsson, R; Nygren, P; Sjöholm, A, 2001
)
0.31
" The pharmacokinetic behaviour of PGBG after intravenous administration (10 mg/kg bodyweight) was studied in five rabbits."( Pharmacokinetic behaviour of phenylglyoxal bis(guanylhydrazone) (PGBG) after intravenous administration in rabbits.
Ballesteros, E; Encinas, T; González, F; Rodríguez, C; San Andrés, MD; San Andrés, MI, 2001
)
0.31
" The method is suitable in pharmacokinetic investigation and monitoring mitoguazone concentration."( Rapid and sensitive quantitation of the antiproliferative agent mitoguazone in small volumes of plasma by high-performance liquid chromatography with ultraviolet detection.
Cheng, CL; Chou, CH; Lin, EG, 2003
)
0.79

Bioavailability

ExcerptReferenceRelevance
"In order to improve the bioavailability of insulin after rectal application to rabbits, the influence of surface-active amino acid-fatty acid condensate on absorption and, the effects of a protease inhibitor (aprotinine), of a disinfectant (methyl-hydroxybenzoate) and of chemotherapeutics (chloramphenicol, ambazone and metronidazole) were investigated."( The protection of insulin against proteolytic processes after rectal application to normoglycemic rabbits.
Hacker, E; Kossowicz, J; Milde, K, 1991
)
0.28
" A "priming" with difluoromethyl ornithine may therefore offer a means to enhance the epidermal accumulation of otherwise poorly absorbed methylglyoxal bis(guanylhydrazone)."( Effect of epidermal polyamine depletion on the accumulation of methylglyoxal bis(guanylhydrazone) in mouse skin.
Jänne, J; Käpyaho, K; Linnamaa, K, 1982
)
0.26
" Our study shows that despite the requirement for controlled storage conditions, the acetate salt solvated form could be an alternative to ambazone when solubility and bioavailability improvement is critical for the clinical efficacy of the drug product."( Crystal structure and physicochemical characterization of ambazone monohydrate, anhydrous, and acetate salt solvate.
Borodi, G; Braga, D; Kacso, I; Maini, L; Muresan-Pop, M; Pop, MM, 2014
)
0.4

Dosage Studied

ExcerptRelevanceReference
" Ultrastructural studies revealed a very close correlation between the dose-response curve for mitochondrial damage and that for MGBG inhibition of mitochondrial DNA synthesis."( A selective effect of methylglyoxal-bis(guanylhydrazone) on the synthesis of mitochondrial DNA of cultured L1210 leukemia cells.
Dave, C; Feuerstein, B; Porter, CW, 1979
)
0.26
" Several experiments suggest that MGBG inhibits cell proliferation by directly blocking polyamine synthesis and not by an unrelated pharmacological effect: (1) the inhibitory action of MGBG is reversed by exogenously added spermidine or spermine; (2) inhibition of DNA synthesis by MGBG shows the same dose-response curve as does inhibition of spermidine and spermine synthesis; and (3) if MGBG is added to cells which have been allowed to accumulate their maximum complement of polyamines, there is no inhibition of thymidine incorporation."( Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A.
Fillingame, RH; Jorstad, CM; Morris, DR, 1975
)
0.25
" Dose-response studies with MGBG (0 to 30 microM for 40 to 48 hr) revealed that, of the parameters related to polyamine metabolism (i."( Biochemical and ultrastructural characterization of human cell variants resistant to the antiproliferative effects of methylglyoxal bis(guanylhydrazone).
Kramer, DL; Porter, CW; Wiseman, A; Zychlinski, L, 1983
)
0.27
" At this dosage and schedule, MGBG has no substantial antitumor activity for patients with non-small cell lung cancer."( Phase II evaluation of MGBG in non-small cell carcinoma of the lung. A Southwest Oncology Group study.
Chen, TT; Costanzi, JJ; Knight, WA; LoBuglio, AF; Vance, RB, 1983
)
0.27
" Both marked antitumor effects and side effects were observed in mice treated at the dosage of DFMO 500 mg/kg/day and/or MGBG 50 mg/kg/day and/or MGBG 30 mg/kg/day brought about significant antitumor effects as well as less side effects."( [Antitumor effects of polyamine synthesis inhibitors based on major premise of treatment for human malignant tumor].
Fujimoto, S; Hirose, S; Igarashi, K; Okui, K; Shrestha, RD; Terao, K, 1982
)
0.26
" This treatment schedule represents much lower dosing of the drug than the earlier daily regimens which were commonly associated with unacceptable toxicity."( Quantitation of methylglyoxal bis(guanylhydrazone) in blood plasma and leukemia cells of patients receiving the drug.
Alhonen-Hongisto, L; Jänne, J; Seppänen, P; Siimes, M, 1980
)
0.26
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
apoptosis inducerAny substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
EC 4.1.1.50 (adenosylmethionine decarboxylase) inhibitorAn EC 4.1.1.* (carboxy-lyase) inhibitor that interferes with the action of adenosylmethionine decarboxylase (EC 4.1.1.50).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
hydrazoneCompounds having the structure R2C=NNR2, formally derived from aldehydes or ketones by replacing =O by =NNH2 (or substituted analogues).
guanidinesAny organonitrogen compound containing a carbamimidamido (guanidino) group. Guanidines have the general structure (R(1)R(2)N)(R(3)R(4)N)C=N-R(5) and are related structurally to amidines and ureas.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Serine/threonine-protein kinase Chk2Homo sapiens (human)IC50 (µMol)20.00000.00300.34823.5000AID1799261
S-adenosylmethionine decarboxylase proenzymeRattus norvegicus (Norway rat)IC50 (µMol)1.00001.00001.00001.0000AID200414
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (28)

Processvia Protein(s)Taxonomy
DNA damage responseSerine/threonine-protein kinase Chk2Homo sapiens (human)
signal transduction in response to DNA damageSerine/threonine-protein kinase Chk2Homo sapiens (human)
DNA damage checkpoint signalingSerine/threonine-protein kinase Chk2Homo sapiens (human)
G2/M transition of mitotic cell cycleSerine/threonine-protein kinase Chk2Homo sapiens (human)
double-strand break repairSerine/threonine-protein kinase Chk2Homo sapiens (human)
regulation of DNA-templated transcriptionSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein phosphorylationSerine/threonine-protein kinase Chk2Homo sapiens (human)
DNA damage responseSerine/threonine-protein kinase Chk2Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestSerine/threonine-protein kinase Chk2Homo sapiens (human)
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediatorSerine/threonine-protein kinase Chk2Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damageSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein catabolic processSerine/threonine-protein kinase Chk2Homo sapiens (human)
mitotic intra-S DNA damage checkpoint signalingSerine/threonine-protein kinase Chk2Homo sapiens (human)
regulation of protein catabolic processSerine/threonine-protein kinase Chk2Homo sapiens (human)
signal transduction in response to DNA damageSerine/threonine-protein kinase Chk2Homo sapiens (human)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatorSerine/threonine-protein kinase Chk2Homo sapiens (human)
positive regulation of DNA-templated transcriptionSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein autophosphorylationSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein stabilizationSerine/threonine-protein kinase Chk2Homo sapiens (human)
cell divisionSerine/threonine-protein kinase Chk2Homo sapiens (human)
thymocyte apoptotic processSerine/threonine-protein kinase Chk2Homo sapiens (human)
cellular response to gamma radiationSerine/threonine-protein kinase Chk2Homo sapiens (human)
mitotic spindle assemblySerine/threonine-protein kinase Chk2Homo sapiens (human)
replicative senescenceSerine/threonine-protein kinase Chk2Homo sapiens (human)
regulation of signal transduction by p53 class mediatorSerine/threonine-protein kinase Chk2Homo sapiens (human)
regulation of autophagosome assemblySerine/threonine-protein kinase Chk2Homo sapiens (human)
mitotic DNA damage checkpoint signalingSerine/threonine-protein kinase Chk2Homo sapiens (human)
polyamine metabolic processS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
spermidine biosynthetic processS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
spermine biosynthetic processS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (11)

Processvia Protein(s)Taxonomy
protein serine/threonine kinase activitySerine/threonine-protein kinase Chk2Homo sapiens (human)
protein bindingSerine/threonine-protein kinase Chk2Homo sapiens (human)
ATP bindingSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein kinase bindingSerine/threonine-protein kinase Chk2Homo sapiens (human)
ubiquitin protein ligase bindingSerine/threonine-protein kinase Chk2Homo sapiens (human)
identical protein bindingSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein homodimerization activitySerine/threonine-protein kinase Chk2Homo sapiens (human)
metal ion bindingSerine/threonine-protein kinase Chk2Homo sapiens (human)
protein serine kinase activitySerine/threonine-protein kinase Chk2Homo sapiens (human)
adenosylmethionine decarboxylase activityS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
protein bindingS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
identical protein bindingS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
putrescine bindingS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (7)

Processvia Protein(s)Taxonomy
chromosome, telomeric regionSerine/threonine-protein kinase Chk2Homo sapiens (human)
nucleoplasmSerine/threonine-protein kinase Chk2Homo sapiens (human)
Golgi apparatusSerine/threonine-protein kinase Chk2Homo sapiens (human)
PML bodySerine/threonine-protein kinase Chk2Homo sapiens (human)
cytoplasmSerine/threonine-protein kinase Chk2Homo sapiens (human)
nucleusSerine/threonine-protein kinase Chk2Homo sapiens (human)
cytosolS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
cytosolS-adenosylmethionine decarboxylase proenzymeHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (63)

Assay IDTitleYearJournalArticle
AID274956Antitumor activity against renal cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID279546Antiproliferative activity against Leishmania donovani DI700 promastigotes2007Antimicrobial agents and chemotherapy, Feb, Volume: 51, Issue:2
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.
AID317500Inhibition of human colon cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID317492Inhibition of human leukemia cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' 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]
AID1130852Anti-leukemic activity against mouse L1210 cells allografted in ip dosed DBA2 mouse assessed as increase in host lifespan administered qd for 1 to 4 days1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones).
AID317498Inhibition of human prostate cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID279551Antiproliferative activity against Leishmania donovani DI700 promastigotes in presence of 100 uM spermidine2007Antimicrobial agents and chemotherapy, Feb, Volume: 51, Issue:2
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.
AID274952Antitumor activity against colon cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID274955Antitumor activity against ovarian cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID274951Antitumor activity against NSCLC cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID317510Induction of cell death in human HL60 cells at 10 uM by propidium iodide staining method2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID274950Antitumor activity against leukemia cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' 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]
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID317499Inhibition of human breast cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID409942Inhibition of human recombinant MAOA by fluorimetric method2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID317508Effect on cell growth in human HL60 cells assessed as cell number per mL at 10 uM2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID317496Inhibition of human ovarian cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID274954Antitumor activity against melanoma cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID317493Inhibition of human non-small cell lung cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
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]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID279547Antiproliferative activity against Leishmania donovani DI700 promastigotes overproducing ODC enzyme2007Antimicrobial agents and chemotherapy, Feb, Volume: 51, Issue:2
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.
AID477025Ratio of IC50 for MGBG polyamine transporter deficient CHO-MG cells to IC50 for CHO cells expressing MGBG polyamine transporter2010European journal of medicinal chemistry, Apr, Volume: 45, Issue:4
Synthesis, cytotoxicity and DNA-binding of novel bisnaphthalimidopropyl derivatives in breast cancer MDA-MB-231 cells.
AID147605Evaluated for inhibition of rat liver ornithine decarboxylase (ODC) at concentrations of 50 uM; No inhibition1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
S-adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogues of methylglyoxal bis(guanylhydrazone).
AID477024Cytotoxicity against MGBG polyamine transporter deficient CHO-MG cells after 48 hrs by MTT assay2010European journal of medicinal chemistry, Apr, Volume: 45, Issue:4
Synthesis, cytotoxicity and DNA-binding of novel bisnaphthalimidopropyl derivatives in breast cancer MDA-MB-231 cells.
AID477023Cytotoxicity against CHO cells expressing MGBG polyamine transporter after 48 hrs by MTT assay2010European journal of medicinal chemistry, Apr, Volume: 45, Issue:4
Synthesis, cytotoxicity and DNA-binding of novel bisnaphthalimidopropyl derivatives in breast cancer MDA-MB-231 cells.
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]
AID317495Inhibition of human melanoma cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID317494Inhibition of human CNS cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID1130855Displacement of ethidium from poly[d(A-T)]-poly[d(A-T)] DNA (unknown origin) by fluorimetric assay1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones).
AID274953Antitumor activity against CNS cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID1130856Displacement of ethidium from poly[d(G-C)]-poly[d(G-C)] DNA (unknown origin) by fluorimetric assay1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones).
AID274958Antitumor activity against breast cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID279548Antiproliferative activity against Leishmania donovani DI700 promastigotes overproducing SPDSYN enzyme2007Antimicrobial agents and chemotherapy, Feb, Volume: 51, Issue:2
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.
AID317502Cell cycle arrest in human HL60 cells assessed as accumulation at G0/G1 phase at 10 uM2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID208534Antiproliferative activity against human T24 bladder carcinoma cells1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
S-adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogues of methylglyoxal bis(guanylhydrazone).
AID274957Antitumor activity against prostate cell lines of the NCI60 panel2006Journal of medicinal chemistry, Dec-28, Volume: 49, Issue:26
Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AID317497Inhibition of human renal cancer cells2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID317504Cell cycle arrest in human HL60 cells assessed as accumulation at S phase at 10 uM2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
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]
AID279549Antiproliferative activity against Leishmania donovani DI700 promastigotes overproducing ADOMETDC enzyme2007Antimicrobial agents and chemotherapy, Feb, Volume: 51, Issue:2
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.
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]
AID279550Antiproliferative activity against Leishmania donovani DI700 promastigotes in presence of 100 uM putrescine2007Antimicrobial agents and chemotherapy, Feb, Volume: 51, Issue:2
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs.
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]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID200226Inhibition of rat liver form of S-adenosyl-methionine decarboxylase enzyme2001Journal of medicinal chemistry, Jan-04, Volume: 44, Issue:1
Terminally alkylated polyamine analogues as chemotherapeutic agents.
AID200414Inhibitory concentration of compound against S-Adenosyl-methionine decarboxylase (SAMDC) from rat liver1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
S-adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogues of methylglyoxal bis(guanylhydrazone).
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID56746In vitro inhibition of Diamine oxidase (DAO) from rat small intestine.1993Journal of medicinal chemistry, Jan-08, Volume: 36, Issue:1
S-adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogues of methylglyoxal bis(guanylhydrazone).
AID1130854Binding affinity to DNA (unknown origin) assessed as decrease in velocity of L1210 DNA-dependent DNA polymerase reaction1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones).
AID317506Cell cycle arrest in human HL60 cells assessed as accumulation at G2/M phase at 10 uM2008Journal of medicinal chemistry, Feb-28, Volume: 51, Issue:4
New antitumor imidazo[2,1-b]thiazole guanylhydrazones and analogues.
AID1130853Anti-leukemic activity against mouse L1210 cells allografted in ip dosed DBA2 mouse assessed as optimum drug dose required for the effect administered qd for 1 to 4 days1979Journal of medicinal chemistry, Oct, Volume: 22, Issue:10
Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones).
AID1799261IMAP High-Throughput Screening from Article 10.1124/mol.107.035832: \\Identification of a Bis-guanylhydrazone [4,4'-Diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase.\\2007Molecular pharmacology, Oct, Volume: 72, Issue:4
Identification of a Bis-guanylhydrazone [4,4'-Diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (637)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990424 (66.56)18.7374
1990's136 (21.35)18.2507
2000's54 (8.48)29.6817
2010's19 (2.98)24.3611
2020's4 (0.63)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.12

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.

MetricThis Compound (vs All)
Research Demand Index18.12 (24.57)
Research Supply Index6.57 (2.92)
Research Growth Index4.10 (4.65)
Search Engine Demand Index21.17 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.12)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials35 (5.16%)5.53%
Reviews31 (4.57%)6.00%
Case Studies12 (1.77%)4.05%
Observational0 (0.00%)0.25%
Other600 (88.50%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Study Characterizing the Impact of Different Therapeutic Strategies on Event Occurrence at 2 Years, 5 Years, 10 Years, and 15 Years, According to Prognostic Groups in Patients With Hodgkin Lymphoma [NCT00920153]Phase 3442 participants (Actual)Interventional2008-05-31Terminated(stopped due to Other new drugs)
Phase II Evaluation of Mitoguazone Dihydrochloride in Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma Associated With Acquired Immunodeficiency Syndrome [NCT00002348]Phase 20 participants InterventionalCompleted
[information is prepared from clinicaltrials.gov, extracted Sep-2024]