Page last updated: 2024-11-12

negamycin

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

Description

negamycin: broad spectrum hydrazide antibiotic obtained from Streptomyces species; action seems to be due to its binding to ribosomes & interference with amino coding in protein synthesis; precursor is probably leucyl-negamycin; minor descriptor (76-85); on-line & Index Medicus search AMINO ACIDS, DIAMINO (76-85); RN given refers to (threo-L)-isomer [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID11118411
CHEMBL ID78628
SCHEMBL ID564074
MeSH IDM0262976

Synonyms (22)

Synonym
CHEMBL78628
acetic acid, (2-(3,6-diamino-5-hydroxyhexanoyl)-1-methylhydrazino)-
33404-78-3
negamycin
l-threo-hexonic acid, 3,6-diamino-2,3,4,6-tetradeoxy-, 2-(carboxymethyl)-2-methylhydrazide
(2-((3r,5r)-3,6-diamino-5-hydroxyhexanoyl)-1-methylhydrazino) acetic acid
brn 4687658
NEG ,
unii-b15l87q2hq
b15l87q2hq ,
SCHEMBL564074
(+)-negamycin
negamycin, (+)-
negamycin [mi]
3,6-diamino-2,3,4,6-tetradeoxy-l-threo-hexonic acid 2-(carboxymethyl)-2-methylhydrazide
'3,6-diamino-1-[2-(carboxymethyl)-2-methylhydrazino]-2,3,4,6-tetradeoxy-l-threo-hexose'
{2-[(3r,5r)-3,6-diamino-5-hydroxyhexanoyl]-1-methylhydrazino}acetic acid (non-preferred name)
Q27274241
2-[[[(3r,5r)-3,6-diamino-5-hydroxyhexanoyl]amino]-methylamino]acetic acid
DTXSID701043349
n-((3r,5r)-3,6-diamino-5-hydroxyhexanamido)-n-methylglycine
AKOS040746151

Research Excerpts

Overview

Negamycin is a natural pseudodipeptide antibiotic with promising activity against Gram-negative and Gram-positive bacteria. Negamycin (NEG) is a ribosome-targeting antibiotic that exhibits clinically promising activity.

ExcerptReferenceRelevance
"Negamycin 1 is a bactericidal antibiotic with activity against Gram-negative bacteria, and served as a template in an antibiotic discovery program. "( N- and C-terminal modifications of negamycin.
Anandan, S; Gao, H; Gomez, M; Hackbarth, C; Mortell, K; O'Dowd, H; Patel, DV; Raju, B; Trias, J; Wang, W; White, R; Wu, C; Yuan, Z, 2003
)
2.04
"Deoxynegamycin (1b) is a protein synthesis inhibitor with activity against Gram-negative (GN) bacteria. "( Conformationally restricted analogs of deoxynegamycin.
Anandan, S; Gomez, M; Gu, S; Hackbarth, C; Herradura, P; Kim, B; O'Dowd, H; Patel, DV; Raju, B; Trias, J; Wang, W; White, R; Wu, C; Yuan, Z, 2004
)
1.1
"Negamycin is a natural product with antibacterial activity against a broad range of Gram-negative pathogens. "( Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
Basarab, GS; Buurman, ET; Cocozaki, AI; Foulk, MA; McKinney, DC; Miller, MD; Narayan, S; Ruvinsky, AM; Scott, CW; Thakur, K; Zhao, L, 2015
)
2.15
"Negamycin is a natural pseudodipeptide antibiotic with promising activity against Gram-negative and Gram-positive bacteria, including "( The Antibiotic Negamycin Crosses the Bacterial Cytoplasmic Membrane by Multiple Routes.
Bendas, G; Berscheid, A; Brötz-Oesterhelt, H; Ciglia, C; Falkenstein-Paul, H; Glüsenkamp, KH; Haustedt, LO; Hörömpöli, D, 2021
)
2.42
"Negamycin (NEG) is a ribosome-targeting antibiotic that exhibits clinically promising activity. "( Negamycin interferes with decoding and translocation by simultaneous interaction with rRNA and tRNA.
Gupta, P; Jiang, F; Mankin, AS; Matsuda, R; Polikanov, YS; Shiozuka, M; Steitz, TA; Szal, T; Vázquez-Laslop, N, 2014
)
3.29
"Negamycin is a natural product with broad-spectrum antibacterial activity and efficacy in animal models of infection. "( Negamycin induces translational stalling and miscoding by binding to the small subunit head domain of the Escherichia coli ribosome.
Altman, RB; Basarab, GS; Blanchard, SC; Buurman, ET; Cate, JH; Code, E; Ferguson, AD; Gao, N; Huang, J; Juette, MF; Livchak, S; Miller, MD; Noeske, J; Olivier, NB; Prince, DB, 2014
)
3.29

Effects

ExcerptReferenceRelevance
"2. Negamycin has a dipeptide-like structure with logD7.4 < -1, causing low permeation into Caco-2 cells, low-oral bioavailability in rats of 6% and low-plasma protein binding of 10% in mouse, rat, dog and human plasma."( Pharmacokinetics of the natural antibiotic negamycin.
Buurman, ET; Chen, A; Guo, J; Luzietti, RA; Miele, EW; Walsky, RL; Zambrowski, M, 2015
)
1.19

Pharmacokinetics

ExcerptReferenceRelevance
" The similar behavior in multiple animal species allowed for the prediction of systemic clearance and volume of distribution in humans using multiple-scaling methods and physiological-based pharmacokinetic modeling and simulation."( Pharmacokinetics of the natural antibiotic negamycin.
Buurman, ET; Chen, A; Guo, J; Luzietti, RA; Miele, EW; Walsky, RL; Zambrowski, M, 2015
)
0.68

Bioavailability

ExcerptReferenceRelevance
"4 < -1, causing low permeation into Caco-2 cells, low-oral bioavailability in rats of 6% and low-plasma protein binding of 10% in mouse, rat, dog and human plasma."( Pharmacokinetics of the natural antibiotic negamycin.
Buurman, ET; Chen, A; Guo, J; Luzietti, RA; Miele, EW; Walsky, RL; Zambrowski, M, 2015
)
0.68
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (25)

Assay IDTitleYearJournalArticle
AID1570878Induction of read through activity at premature termination codon TAA (non-sense mutation associated with DMD disease) in 27-mer DNA stretch sequence of mouse dystrophin mdx gene transfected as a plasmid by connecting with beta-galactosidase and luciferas2019ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10
New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
AID1570877Induction of read through activity at premature termination codon TAG (non-sense mutation associated with DMD disease) in 27-mer DNA stretch sequence of mouse dystrophin mdx gene transfected as a plasmid by connecting with beta-galactosidase and luciferas2019ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10
New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
AID68192In vitro antibacterial activity against Enterobacter cloacae ATCC 350302003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID96252In vitro antibacterial activity against Klebsiella pneumoniae ATCC 1138822003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID70906In vitro antibacterial activity against Escherichia coli MG1655 tolC2003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID210224In vitro antibacterial activity against Streptococcus pneumoniae VSPN10052003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID130536In vivo efficacy in Escherichia coli murine septicemia model2003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID70905In vitro antibacterial activity against Escherichia coli MG16552003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID206140In vitro antibacterial activity against Staphylococcus aureus ATCC 252932003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID1230793Mutation read through activity in african green monkey COS7 cells transfected with dual-reporter plasmid encoding beta-galactosidase and luciferase genes connected with TGA-containing mouse mdx gene exon 23 nucleotide sequence as premature termination cod2015ACS medicinal chemistry letters, Jun-11, Volume: 6, Issue:6
Structure-Activity Relationship Studies of 3-epi-Deoxynegamycin Derivatives as Potent Readthrough Drug Candidates.
AID1503964Mutation read through activity at premature termination codon TGA-containing mouse dystrophin gene exon 23 nucleotide sequence expressed in African green monkey COS7 cells assessed as ratio of luciferase activity to beta-galactosidase activity at 200 uM a2017ACS medicinal chemistry letters, Oct-12, Volume: 8, Issue:10
Structure-Activity Relationship Study of Leucyl-3-
AID1570876Induction of read through activity at premature termination codon TGA (non-sense mutation associated with DMD disease) in 27-mer DNA stretch sequence of mouse dystrophin mdx gene transfected as a plasmid by connecting with beta-galactosidase and luciferas2019ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10
New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
AID1250082Inhibition of transcription-translation process in Escherichia coli2015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250085Antibacterial activity against Escherichia coli ATCC 259222015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID69133Inhibitory activity against protein synthesis of Escherichia coli S30 by cell-free transcription/translation coupled assay2003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID70904In vitro antibacterial activity against Escherichia coli ATCC 259222003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID165053In vitro antibacterial activity against Pseudomonas aeruginosa PA0132003Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14
N- and C-terminal modifications of negamycin.
AID1586840Induction of read through activity at cricket paralysis virus-internal ribosome entry site codon UGG assessed as increase in octapeptide formation from FKVRQ-tRNAGln at EC50 to 2 times EC50 measured after 20 mins in presence of Typ-tRNA, Leu-tRNA and [35S2018ACS medicinal chemistry letters, Dec-13, Volume: 9, Issue:12
New
AID1250088Antibacterial activity against mexABCDXY-deficient Pseudomonas aeruginosa PAO12015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250086Antibacterial activity against Pseudomonas aeruginosa PAO12015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250083Antibacterial activity against Acinetobacter baumannii ARC 34952015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID114652Compound was evaluated for its efficacy in an Escherichia coli murine septicemia model2004Bioorganic & medicinal chemistry letters, Jun-21, Volume: 14, Issue:12
Conformationally restricted analogs of deoxynegamycin.
AID1250084Antibacterial activity against Klebsiella pneumoniae ATCC 7006032015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250087Antibacterial activity against tolC-deficient Escherichia coli ATCC 259222015ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8
Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1586839Induction of read through activity at cricket paralysis virus-internal ribosome entry site premature termination codon UGA assessed as ratio of plateau octapeptide to FKVRQ-tRNAGln measured after 20 mins in presence of Typ-tRNA, Leu-tRNA and [35S]-Met-tRN2018ACS medicinal chemistry letters, Dec-13, Volume: 9, Issue:12
New
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (31)

TimeframeStudies, This Drug (%)All Drugs %
pre-19906 (19.35)18.7374
1990's0 (0.00)18.2507
2000's10 (32.26)29.6817
2010's14 (45.16)24.3611
2020's1 (3.23)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.67

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 Index25.67 (24.57)
Research Supply Index3.47 (2.92)
Research Growth Index4.46 (4.65)
Search Engine Demand Index29.35 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.67)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews5 (16.13%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other26 (83.87%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]