Page last updated: 2024-12-08

sjg 136

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

Description

1,1'-((propane-1,3-diyl)dioxy)bis(7-methoxy-2-methylidene-1,2,3,10,11,11a-hexahydro-5H-pyrrolo(2,1-c)(1,4)benzodiazepin-5,11-dione): structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID393111
CHEMBL ID16498
SCHEMBL ID12020905
MeSH IDM0475187

Synonyms (35)

Synonym
sjg 136
232931-57-6
NCI60_033825
up 2001
nsc694501
nsc-694501
5h-pyrrolo[2,4]benzodiazepin-5-one, 8,8'-[1,3-propanediylbis(oxy)]bis[1,2,3,11a-tetrahydro- 7-methoxy-2-methylene-, (11as, 11'as)-
sg-2000
sjg-136
CHEMBL16498
up-2001
sp-2001
bn-2629
(6as)-3-[3-[[(6as)-2-methoxy-8-methylidene-11-oxo-7,9-dihydro-6ah-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-2-methoxy-8-methylidene-7,9-dihydro-6ah-pyrrolo[2,1-c][1,4]benzodiazepin-11-one
kt0zq64x1a ,
unii-kt0zq64x1a
sjg136
1,1'-((propane-1,3-diyl)dioxy)bis(7-methoxy-2-methylidene-1,2,3,10,11,11a-hexahydro-5h-pyrrolo(2,1-c)(1,4)benzodiazepin-5,11-dione)
nsc 694501
CS-4593
SCHEMBL12020905
HY-14573
sjg 136 [who-dd]
(6as)-3-(3-(((6as)-2-methoxy-8-methylene-11-oxo-7,9-dihydro-6ah-pyrrolo(2,1-c)(1,4)benzodiazepin-3-yl)oxy)propoxy)-2-methoxy-8-methylene-7,9-dihydro-6ah-pyrrolo(2,1-c)(1,4)benzodiazepin-11-one
5h-pyrrolo(2,1-c)(1,4)benzodiazepin-5-one, 8,8'-(1,3-propanediylbis(oxy))bis(1,2,3,11a-tetrahydro-7-methoxy-2-methylene-, (11as,11'as)-
DTXSID20177864
AKOS027326601
DB11965
(11as,11a's)-8,8'-(propane-1,3-diylbis(oxy))bis(7-methoxy-2-methylene-1,2,3,11a-tetrahydro-5h-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one)
5h-pyrrolo[2,1-c][1,4]benzodiazepin-5-one, 8,8'-[1,3-propanediylbis(oxy)]bis[1,2,3,11a-tetrahydro-7-methoxy-2-methylene-, (11as,11'as)-
Q27282424
C74198
A858346
(11as,11a's)-8,8'-(propane-1,3-diylbis(oxy))bis(7-methoxy-2-methylene-1,2,3,11a-tetrahydro-5h-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one);1,1'-(propane-1,3-diylbis(oxy))bis(7-methoxy-2-methylene-1,2,3,11a-tetrahydro-5h-benzo[e]pyrrolo[1,2-a][1,4]diazepine-
BS-42683

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" This study examines the pharmacological characteristics of SJG-136 and provides the first report of pharmacokinetic properties for this agent."( Preliminary pharmacokinetic and bioanalytical studies of SJG-136 (NSC 694501), a sequence-selective pyrrolobenzodiazepine dimer DNA-cross-linking agent.
Cooper, P; Howard, PW; Jenkins, TC; Loadman, PM; Shnyder, S; Taylor, JP; Thurston, DE; Wilkinson, GP, 2004
)
0.32
" Following treatment with an intraperitoneal injection, fibres were excised and cells retrieved for pharmacodynamic analysis using the comet assay/fluorescence microscopy."( The hollow fibre model--facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare.
Bibby, MC; Cooper, PA; Shnyder, SD; Suggitt, M, 2006
)
0.33
"To evaluate γ-H2AX foci as a pharmacodynamic marker for DNA damage induced by DNA interstrand cross-linking drugs."( γ-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000).
Clingen, PH; Hartley, JA; Hochhauser, D; Jodrell, D; Mellinas-Gomez, M; Meyer, T; Puzanov, I; Spanswick, VJ; Wu, J, 2013
)
0.39
" An increased γ-H2AX response was observed during the second cycle consistent with a cumulative pharmacodynamic effect."( γ-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000).
Clingen, PH; Hartley, JA; Hochhauser, D; Jodrell, D; Mellinas-Gomez, M; Meyer, T; Puzanov, I; Spanswick, VJ; Wu, J, 2013
)
0.39
"This is the first use of γ-H2AX as a pharmacodynamic response to a DNA cross-linking agent in a clinical trial setting."( γ-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000).
Clingen, PH; Hartley, JA; Hochhauser, D; Jodrell, D; Mellinas-Gomez, M; Meyer, T; Puzanov, I; Spanswick, VJ; Wu, J, 2013
)
0.39

Dosage Studied

ExcerptRelevanceReference
" Alternative clinical dosing strategies are being evaluated."( Phase I study of sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors.
Begent, RH; Clingen, PH; Cobb, M; Gumbrell, L; Hartley, JA; Hochhauser, D; Jodrell, D; Loadman, P; Meyer, T; Spanswick, VJ; Wu, J, 2009
)
0.35
" Alternative dosing strategies are now being evaluated."( A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors.
Azzoli, CG; Calcutt, MW; Janjigian, YY; Kris, MG; Krug, LM; Lee, W; Miller, VA; Rizvi, NA; Senturk, E, 2010
)
0.36
" Substantial changes in volume of distribution at steady-state occurred after repeated dosing in some patients prior to the onset of edema."( Phase I pharmacokinetic and pharmacodynamic study of SJG-136, a novel DNA sequence selective minor groove cross-linking agent, in advanced solid tumors.
Berlin, JD; Calcutt, MW; Chen, AP; Hachey, DL; Hartley, JA; Lee, W; Liao, CY; Puzanov, I; Rothenberg, ML; Spanswick, VJ; Vermeulen, WL, 2011
)
0.37
"γ-H2AX foci formation was validated preclinically in comparison with the Comet assay, and evaluated pharmacodynamically in two phase I studies of different dosing schedules of the novel cross-linking agent SJG-136 (SG2000)."( γ-H2AX foci formation as a pharmacodynamic marker of DNA damage produced by DNA cross-linking agents: results from 2 phase I clinical trials of SJG-136 (SG2000).
Clingen, PH; Hartley, JA; Hochhauser, D; Jodrell, D; Mellinas-Gomez, M; Meyer, T; Puzanov, I; Spanswick, VJ; Wu, J, 2013
)
0.39
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (30)

Assay IDTitleYearJournalArticle
AID224602Compound dose required to induce 50 percent cross linking in naked plasmid pBR322 DNA following incubation with agent for 2 hours at 37 degree C2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID94620Dose required to induce 50 percent decrease in tail moment of the DNA of K562 cells following a 1 hour treatment2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID321351Cytotoxicity against human NCI60 cells2008Bioorganic & medicinal chemistry letters, Mar-15, Volume: 18, Issue:6
An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA interstrand cross-linking agent spanning 11 DNA base pairs.
AID471718Cytotoxicity against human K562 cells by alamar blue assay2009Bioorganic & medicinal chemistry letters, Nov-15, Volume: 19, Issue:22
Synthesis of a novel C2/C2'-aryl-substituted pyrrolo[2,1-c][1,4]benzodiazepine dimer prodrug with improved water solubility and reduced DNA reaction rate.
AID392957Binding affinity to calf thymus DNA assessed as change in melting temperature at a compound to DNA molar ratio of 1:5 at pH 7 by thermal denaturation assay2009Bioorganic & medicinal chemistry, Feb-15, Volume: 17, Issue:4
Remarkable enhancement in the DNA-binding ability of C2-fluoro substituted pyrrolo[2,1-c][1,4]benzodiazepines and their anticancer potential.
AID54323Thermal stabilization of duplex form of calf thymus DNA after incubation for 0 hours2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID230366Resistance factor (IC50 resistant/ parent)2001Bioorganic & medicinal chemistry letters, Nov-05, Volume: 11, Issue:21
Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer.
AID10018Growth inhibition in human ovarian carcinoma cell line (A2780cisR,cisplatin-resistant) using the 96 hour exposure sulforhodamine B (SRB) growth delay assay2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID94817Inhibitory concentration against human K562 leukemia cells following incubation for 1 hour2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID47514Inhibition of cell growth in human ovarian carcinoma cell line (CH1-cis-R,cisplatin resistant) using the 96 hour continuous exposure sulforhodamine B (SRB) growth delay assay2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID202838Inhibition of cell growth in human ovarian carcinoma cell line(SKOV-3) using the 96 hour continuous exposure sulforhodamine B (SRB) growth delay assay2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID232613Ratio of IC50 against human ovarian carcinoma cell line (CH1)cisR (cisplatin resistant) to the IC50 of parent2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID249980Increase in melting point temperature after 18 hr of incubation [1:5] as measurement of DNA binding affinity using calf thymus DNA2004Bioorganic & medicinal chemistry letters, Nov-15, Volume: 14, Issue:22
Synthesis of fluorinated analogues of SJG-136 and their DNA-binding potential.
AID321352Cytotoxicity against human K562 cells2008Bioorganic & medicinal chemistry letters, Mar-15, Volume: 18, Issue:6
An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA interstrand cross-linking agent spanning 11 DNA base pairs.
AID276048Induction of linear pBR322 DNA interstrand crosslinking2006Bioorganic & medicinal chemistry letters, Nov-01, Volume: 16, Issue:21
DNA interstrand crosslinking agents: synthesis, DNA interactions, and cytotoxicity of dimeric achiral seco-amino-CBI and conjugates of achiral seco-amino-CBI with pyrrolobenzodiazepine (PBD).
AID270008Cytotoxicity against human NCI60 cell line by MTT assay2006Journal of medicinal chemistry, Sep-07, Volume: 49, Issue:18
Design, synthesis, and biophysical and biological evaluation of a series of pyrrolobenzodiazepine-poly(N-methylpyrrole) conjugates.
AID54325Thermal stabilization of duplex form of calf thymus DNA after incubation for 4 hours2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID321353Induction of cross linking in DS pUC18 plasmid2008Bioorganic & medicinal chemistry letters, Mar-15, Volume: 18, Issue:6
An asymmetric C8/C8'-tripyrrole-linked sequence-selective pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer DNA interstrand cross-linking agent spanning 11 DNA base pairs.
AID10017Dose of required to inhibit growth of human ovarian carcinoma (A2780) cell line with compound free controls as measured by the sulforhodamine B growth delay assay2001Bioorganic & medicinal chemistry letters, Nov-05, Volume: 11, Issue:21
Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer.
AID270012Cytotoxicity against human K562 cell line after 96 hrs by MTT assay2006Journal of medicinal chemistry, Sep-07, Volume: 49, Issue:18
Design, synthesis, and biophysical and biological evaluation of a series of pyrrolobenzodiazepine-poly(N-methylpyrrole) conjugates.
AID41578Compound was tested for inhibition of restriction endonuclease BamH1 enzyme at a concentration of 17.5 uM;Inhibited2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID225423The concentration of compound required for 50% cross linking of plasmid pBR322 DNA was investigated using an assay involving linear double stranded DNA2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID249982Increase in melting point temperature after 0h of incubation [1:5 ratio] as measurement of DNA binding affinity using calf thymus DNA2004Bioorganic & medicinal chemistry letters, Nov-15, Volume: 14, Issue:22
Synthesis of fluorinated analogues of SJG-136 and their DNA-binding potential.
AID9821Inhibition of cell growth in human ovarian carcinoma cell line (A2780) using the 96 hour continuous exposure sulforhodamine B (SRB) growth delay assay2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID47512Inhibition of cell growth in human ovarian carcinoma cell line (CH1) was determined using the 96 hour continuous exposure sulforhodamine B (SRB) growth delay assay.2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID94467Inhibition of cell growth by 50% in human leukemia cell line (K562) was determined using microculture tetrazolium (MTT) assay.2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID232609Ratio of IC50 against A2780cisR (cisplatin resistant) to the IC50 of parent2001Journal of medicinal chemistry, Mar-01, Volume: 44, Issue:5
Design, synthesis, and evaluation of a novel pyrrolobenzodiazepine DNA-interactive agent with highly efficient cross-linking ability and potent cytotoxicity.
AID10016Dose of required to inhibit growth of cisplatin resistant human ovarian carcinoma (A2780 cisR) cell line with compound free controls as measured by the sulforhodamine B growth delay assay2001Bioorganic & medicinal chemistry letters, Nov-05, Volume: 11, Issue:21
Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer.
AID54324Thermal stabilization of duplex form of calf thymus DNA after incubation for 18 hours2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (37)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's27 (72.97)29.6817
2010's9 (24.32)24.3611
2020's1 (2.70)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 21.19

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 Index21.19 (24.57)
Research Supply Index3.71 (2.92)
Research Growth Index4.32 (4.65)
Search Engine Demand Index21.17 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (21.19)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (8.11%)5.53%
Reviews2 (5.41%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other32 (86.49%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]