Page last updated: 2024-11-07

duocarmycin sa

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

Description

duocarmycin SA: structure similar to CC-1065 and yatakemycin, composed of a pyrrolo-indole plus an indole; isolated from Streptomyces [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID115369
CHEMBL ID308086
SCHEMBL ID61916
MeSH IDM0181506

Synonyms (14)

Synonym
duocarmycin sa
antibiotic dc113
cyclopropa(c)pyrrolo(3,2-e)indole-6-carboxylic acid, 1,2,4,5,8,8a-hexahydro-4-oxo-2-((5,6,7-trimethoxy-1h-indol-2-yl)carbonyl)-, methyl ester, (7br)-
(+)-duocarmycin sa
CHEMBL308086
130288-24-3
SCHEMBL61916
DTXSID30926663
AKOS032946598
EX-A7932
methyl (1r,12s)-7-oxo-10-(5,6,7-trimethoxy-1h-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-4-carboxylate
CS-0011400
HY-12456
duocarmycinsa

Research Excerpts

Overview

Duocarmycin SA is a member of a growing class of interesting lead compounds for chemotherapy. It is distinguished by the manner in which they bind to and react with DNA substrates.

ExcerptReferenceRelevance
"Duocarmycin SA is a member of a growing class of interesting lead compounds for chemotherapy, distinguished by the manner in which they bind to and react with DNA substrates. "( The structural basis for in situ activation of DNA alkylation by duocarmycin SA.
Bifulco, G; Boger, DL; Case, DA; Chazin, WJ; Gomez-Paloma, L; Smith, JA, 2000
)
1.99

Effects

ExcerptReferenceRelevance
"New duocarmycin SA derivatives have been synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells, and in vivo antitumor activity against murine sarcoma 180 in mice. "( Studies on duocarmycin SA and its derivatives.
Asai, A; Gomi, K; Kobayashi, E; Nagamura, S; Saito, H, 1997
)
1.24

Compound-Compound Interactions

ExcerptReferenceRelevance
" Here, the lacZ-carrying vaccinia virus (VACV) strain GLV-1h68 was used in combination with a β-galactosidase-activatable prodrug derived from a seco-analog of the natural antibiotic duocarmycin SA."( Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA.
Chen, N; Donat, U; Gentschev, I; Hess, M; Krewer, B; Seubert, CM; Stritzker, J; Sturm, JB; Szalay, AA; Tietze, LF; von Hof, JM, 2011
)
0.76

Dosage Studied

ExcerptRelevanceReference
" In vivo evaluation of the prodrug 6 showed that it exhibits extraordinary efficacy (T/C > 1500, L1210; 6/10 one year survivors), substantially exceeding that of the free drug, that its therapeutic window of activity is much larger, permitting a dosing ≥ 40-fold higher than the free drug, and yet that it displays a potency in vivo that approaches the free drug (within 3-fold)."( Efficacious cyclic N-acyl O-amino phenol duocarmycin prodrugs.
Boger, DL; Brown, D; Duncan, KK; Parelkar, NK; Vielhauer, GA; Wolfe, AL, 2013
)
0.39
" This in turn permitted elevated dosing levels, leading to higher systemic exposure and a significantly improved response in tumor xenograft models."( A Novel Tumor-Activated Prodrug Strategy Targeting Ferrous Iron Is Effective in Multiple Preclinical Cancer Models.
Fontaine, SD; Hann, B; Mattis, AN; Renslo, AR; Sambucetti, L; Shi, Y; Spangler, B; Wells, JA, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (35)

Assay IDTitleYearJournalArticle
AID1395997Cytotoxicity against human U138MG cells assessed as cell survival at 0.5 nM after 72 hrs by trypan blue dye based assay2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID537230Cytotoxicity against mouse L1210 cells2010Journal of medicinal chemistry, Nov-11, Volume: 53, Issue:21
Design, synthesis, and evaluation of duocarmycin O-amino phenol prodrugs subject to tunable reductive activation.
AID1396000Cytotoxicity against human U138MG cells assessed as dose enhancement ratio at 0.1 nM after 72 hrs in presence of 2 Gy dose of proton irradiation by trypan blue dye based assay2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID512680Induction of thermal cleavage in protein free alpha satellite DNA 5'-GGAAAC-3' at 10 uM at 25 degC after 17 hrs by non-denaturating gel electrophoresis2006Nature chemical biology, Feb, Volume: 2, Issue:2
Alkylation of duplex DNA in nucleosome core particles by duocarmycin SA and yatakemycin.
AID1635392Induction of alkylation at Simian virus 40 150-bp DNA w794 after 24 hrs by PAGE and autoradiography method2016Bioorganic & medicinal chemistry, 10-15, Volume: 24, Issue:20
Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) alkylation subunit.
AID1396011Anticlonogenic activity against human U138MG cells assessed as dose enhancement ratio pretreated for 2 hrs followed by 1 to 8 Gy dose of proton irradiation measured after 10 to 14 days by methylene blue staining based method2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID431576Stability assessed as half life at pH 72009Journal of medicinal chemistry, Oct-08, Volume: 52, Issue:19
Fundamental relationships between structure, reactivity, and biological activity for the duocarmycins and CC-1065.
AID431574Cytotoxicity against mouse L1210 cells2009Journal of medicinal chemistry, Oct-08, Volume: 52, Issue:19
Fundamental relationships between structure, reactivity, and biological activity for the duocarmycins and CC-1065.
AID464157Alkylation of cell free 32p end labeled double stranded w794 DNA at 10 uM after 48 hrs by PAGE and autoradiography2010Bioorganic & medicinal chemistry letters, Mar-15, Volume: 20, Issue:6
Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]oxazolo[2,3-e]indol-4-one-6-carboxylate (COI) alkylation subunit.
AID1396009Anticlonogenic activity against human U138MG cells assessed as decrease in cell survival pretreated for 2 hrs followed by 1 to 8 Gy dose of proton irradiation measured after 10 to 14 days by methylene blue staining based method2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID1395999Cytotoxicity against human U138MG cells assessed as decrease in cell viability after 72 hrs by trypan blue dye based assay2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID512675Induction of thermal cleavage in alpha satellite DNA at 10 uM at 25 degC after 1 hr by non-denaturating gel electrophoresis2006Nature chemical biology, Feb, Volume: 2, Issue:2
Alkylation of duplex DNA in nucleosome core particles by duocarmycin SA and yatakemycin.
AID464156Cytotoxicity against mouse L1210 cells2010Bioorganic & medicinal chemistry letters, Mar-15, Volume: 20, Issue:6
Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]oxazolo[2,3-e]indol-4-one-6-carboxylate (COI) alkylation subunit.
AID1396010Anticlonogenic activity against human U138MG cells assessed as cell survival at 0.001 nM pretreated for 2 hrs followed by 1 to 8 Gy dose of proton irradiation measured after 10 to 14 days by methylene blue staining based method2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID1635390Cytotoxicity against mouse L1210 cells assessed as cell growth inhibition2016Bioorganic & medicinal chemistry, 10-15, Volume: 24, Issue:20
Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]imidazolo[4,5-e]indol-4-one-6-carboxylate (CImI) alkylation subunit.
AID1396002Induction of apoptosis in human U138MG cells at 0.1 nM after 72 hrs by Annexin V staining based flow cytometry2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID464158Alkylation of cell free 32p end labeled double stranded w794 DNA at 100 uM after 48 hrs by PAGE and autoradiography2010Bioorganic & medicinal chemistry letters, Mar-15, Volume: 20, Issue:6
Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]oxazolo[2,3-e]indol-4-one-6-carboxylate (COI) alkylation subunit.
AID98333In vitro cytotoxicity against L1210 cell line2000Bioorganic & medicinal chemistry letters, Mar-06, Volume: 10, Issue:5
Bifunctional alkylating agents derived from duocarmycin SA: potent antitumor activity with altered sequence selectivity.
AID1396003Induction of necrosis in human U138MG cells at 0.1 nM after 72 hrs by 7-AAD staining based flow cytometry2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID1396005Induction of necrosis in human U138MG cells at 0.1 nM after 72 hrs in presence of 6 Gy dose of proton irradiation by 7-AAD staining based flow cytometry2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID740033Cytotoxicity against mouse L1210 cells assessed as growth inhibition after 72 hrs by phosphatase assay2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Efficacious cyclic N-acyl O-amino phenol duocarmycin prodrugs.
AID470790Cytotoxicity against mouse L1210 cells2009Bioorganic & medicinal chemistry letters, Dec-15, Volume: 19, Issue:24
Synthesis and evaluation of a thio analogue of duocarmycin SA.
AID1396006Induction of apoptosis in human U138MG cells assessed as dose enhancement ratio at 0.1 nM after 72 hrs in presence of 2 Gy dose of proton irradiation by Annexin V staining based flow cytometry2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID470791Induction of w794 DNA alkylation at 10 uM after 24 hrs by PAGE2009Bioorganic & medicinal chemistry letters, Dec-15, Volume: 19, Issue:24
Synthesis and evaluation of a thio analogue of duocarmycin SA.
AID1396004Induction of apoptosis in human U138MG cells at 0.1 nM after 72 hrs in presence of 6 Gy dose of proton irradiation by Annexin V staining based flow cytometry2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID1395996Cytotoxicity against human U138MG cells assessed as cell survival at 0.1 nM after 72 hrs by trypan blue dye based assay2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID1396007Induction of necrosis in human U138MG cells assessed as dose enhancement ratio at 0.1 nM after 72 hrs in presence of 2 Gy dose of proton irradiation by 7-AAD staining based flow cytometry2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID512676Induction of thermal cleavage in alpha satellite DNA at 10 uM at 25 degC after 30 mins by non-denaturating gel electrophoresis2006Nature chemical biology, Feb, Volume: 2, Issue:2
Alkylation of duplex DNA in nucleosome core particles by duocarmycin SA and yatakemycin.
AID1395998Cytotoxicity against human U138MG cells assessed as cell survival at higher doses after 72 hrs by trypan blue dye based assay2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID482107Cytotoxicity against mouse L1210 cells2010Bioorganic & medicinal chemistry letters, May-01, Volume: 20, Issue:9
Synthesis and evaluation of a series of C5'-substituted duocarmycin SA analogs.
AID431575Stability assessed as half life at pH 32009Journal of medicinal chemistry, Oct-08, Volume: 52, Issue:19
Fundamental relationships between structure, reactivity, and biological activity for the duocarmycins and CC-1065.
AID512677Binding affinity to alpha satellite DNA assessed as neucleosome reconstitution after 17 hrs at 25 degC by non-denaturating gel electrophoresis2006Nature chemical biology, Feb, Volume: 2, Issue:2
Alkylation of duplex DNA in nucleosome core particles by duocarmycin SA and yatakemycin.
AID1396001Cytotoxicity against human U138MG cells assessed as decrease in cell viability at 0.5 to 1 nM after 72 hrs in presence of 2 Gy dose of proton irradiation by trypan blue dye based assay2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
AID690883Cytotoxicity against mouse L1210 cells2012Journal of medicinal chemistry, Jun-28, Volume: 55, Issue:12
A novel, unusually efficacious duocarmycin carbamate prodrug that releases no residual byproduct.
AID1396008Anticlonogenic activity against human U138MG cells assessed as decrease in cell survival after 14 days by methylene blue staining based method2018Bioorganic & medicinal chemistry letters, 09-01, Volume: 28, Issue:16
Duocarmycin SA, a potent antitumor antibiotic, sensitizes glioblastoma cells to proton radiation.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (75)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's11 (14.67)18.2507
2000's44 (58.67)29.6817
2010's19 (25.33)24.3611
2020's1 (1.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 19.61

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 Index19.61 (24.57)
Research Supply Index4.33 (2.92)
Research Growth Index4.65 (4.65)
Search Engine Demand Index18.60 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (19.61)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews5 (6.67%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other70 (93.33%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]