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 Source	ID
PubMed CID	11118411
CHEMBL ID	78628
SCHEMBL ID	564074
MeSH ID	M0262976

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.

Excerpt	Reference	Relevance
"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

Excerpt	Reference	Relevance
"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

Excerpt	Reference	Relevance
" 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

Excerpt	Reference	Relevance
"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 ID	Title	Year	Journal	Article
AID1570878	Induction 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 luciferas	2019	ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10	New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
AID1570877	Induction 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 luciferas	2019	ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10	New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
AID68192	In vitro antibacterial activity against Enterobacter cloacae ATCC 35030	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID96252	In vitro antibacterial activity against Klebsiella pneumoniae ATCC 113882	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID70906	In vitro antibacterial activity against Escherichia coli MG1655 tolC	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID210224	In vitro antibacterial activity against Streptococcus pneumoniae VSPN1005	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID130536	In vivo efficacy in Escherichia coli murine septicemia model	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID70905	In vitro antibacterial activity against Escherichia coli MG1655	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID206140	In vitro antibacterial activity against Staphylococcus aureus ATCC 25293	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID1230793	Mutation 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 cod	2015	ACS medicinal chemistry letters, Jun-11, Volume: 6, Issue:6	Structure-Activity Relationship Studies of 3-epi-Deoxynegamycin Derivatives as Potent Readthrough Drug Candidates.
AID1503964	Mutation 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 a	2017	ACS medicinal chemistry letters, Oct-12, Volume: 8, Issue:10	Structure-Activity Relationship Study of Leucyl-3-
AID1570876	Induction 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 luciferas	2019	ACS medicinal chemistry letters, Oct-10, Volume: 10, Issue:10	New Negamycin-Based Potent Readthrough Derivative Effective against TGA-Type Nonsense Mutations.
AID1250082	Inhibition of transcription-translation process in Escherichia coli	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250085	Antibacterial activity against Escherichia coli ATCC 25922	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID69133	Inhibitory activity against protein synthesis of Escherichia coli S30 by cell-free transcription/translation coupled assay	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID70904	In vitro antibacterial activity against Escherichia coli ATCC 25922	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID165053	In vitro antibacterial activity against Pseudomonas aeruginosa PA013	2003	Bioorganic & medicinal chemistry letters, Jul-21, Volume: 13, Issue:14	N- and C-terminal modifications of negamycin.
AID1586840	Induction 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 [35S	2018	ACS medicinal chemistry letters, Dec-13, Volume: 9, Issue:12	New
AID1250088	Antibacterial activity against mexABCDXY-deficient Pseudomonas aeruginosa PAO1	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250086	Antibacterial activity against Pseudomonas aeruginosa PAO1	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250083	Antibacterial activity against Acinetobacter baumannii ARC 3495	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID114652	Compound was evaluated for its efficacy in an Escherichia coli murine septicemia model	2004	Bioorganic & medicinal chemistry letters, Jun-21, Volume: 14, Issue:12	Conformationally restricted analogs of deoxynegamycin.
AID1250084	Antibacterial activity against Klebsiella pneumoniae ATCC 700603	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1250087	Antibacterial activity against tolC-deficient Escherichia coli ATCC 25922	2015	ACS medicinal chemistry letters, Aug-13, Volume: 6, Issue:8	Structural Insights Lead to a Negamycin Analogue with Improved Antimicrobial Activity against Gram-Negative Pathogens.
AID1586839	Induction 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-tRN	2018	ACS 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)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	6 (19.35)	18.7374
1990's	0 (0.00)	18.2507
2000's	10 (32.26)	29.6817
2010's	14 (45.16)	24.3611
2020's	1 (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.

Metric	This Compound (vs All)
Research Demand Index	25.67 (24.57)
Research Supply Index	3.47 (2.92)
Research Growth Index	4.46 (4.65)
Search Engine Demand Index	29.35 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (25.67)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	5 (16.13%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	26 (83.87%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
2-aminoacetaldehyde 2-aminoacetaldehyde: structure. 2-aminoacetaldehyde : An amino aldehyde that is acetaldehyde in which one of the hydrogens of the methyl group has been replaced by an amino group.	2.04	1	amino aldehyde; omega-aminoaldehyde	Escherichia coli metabolite
glycine [no description available]	2.04	1	alpha-amino acid; amino acid zwitterion; proteinogenic amino acid; serine family amino acid	EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor; fundamental metabolite; hepatoprotective agent; micronutrient; neurotransmitter; NMDA receptor agonist; nutraceutical
gentamicin Gentamicins: A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.	3.81	3
isoxazoles Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.. isoxazole : A monocyclic heteroarene with a structure consisting of a 5-membered ring containing three carbon atoms and an oxygen and nitrogen atom adjacent to each other. It is the parent of the class of isoxazoles.. isoxazoles : Oxazoles in which the N and O atoms are adjacent.	2.1	1	isoxazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene
hydrazine diamine : Any polyamine that contains two amino groups.	2.01	1	azane; hydrazines	EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor
showdomycin Showdomycin: 3-beta-D-Ribofuranosylmaleimide. Antineoplastic antibiotic isolated from Streptomyces showdoensis. It is possibly active also as a sulfhydryl reagent.	1.96	1
adenosine quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit	1.96	1	adenosines; purines D-ribonucleoside	analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent
aristeromycin aristeromycin: RN given refers to (1R-(1alpha,2alpha,3beta,5alpha)-isomer	1.96	1
arbekacin arbekacin: structure given in first source. arbekacin : A kanamycin that is kanamycin B bearing an N-(2S)-4-amino-2-hydroxybutyryl group on the aminocyclitol ring.	2.15	1	aminoglycoside; kanamycins	antibacterial agent; antibacterial drug; antimicrobial agent; protein synthesis inhibitor
neplanocin a neplanocin A: neplanocins are antitumor antibiotics & carbocyclic analogs of purine nucleosides from Ampullarilla regularis A11079; see also neplanocin B, neplanocin C, neplanocin D & neplanocin F; structure in first source; a potent inhibitor of S-adenosylhomocysteine hydrolase	1.96	1
antibiotic g 418 antibiotic G 418: from Micromonospora rhodorangea	2.11	1
thienamycin thienamycin: beta-lactam antibiotic; RN given refers to cpd without isomeric designation	1.96	1	carbapenems
zithromax Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.. azithromycin : A macrolide antibiotic useful for the treatment of bacterial infections.	2.17	1	macrolide antibiotic	antibacterial drug; environmental contaminant; xenobiotic
tylosin [no description available]	2.17	1	aldehyde; disaccharide derivative; enone; leucomycin; macrolide antibiotic; monosaccharide derivative	allergen; bacterial metabolite; environmental contaminant; xenobiotic
asparenomycin asparenomycin: from Streptomyces tokunonensis sp. nov.; structure given in first source	1.96	1
carpetimycin a carpetimycin A: from Streptomyces sp. KC-6643; structure given in first source	1.96	1
gentamicin sulfate [no description available]	2.11	1
oxadiazoles Oxadiazoles: Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.	3.17	1
ptc 124 [no description available]	3.61	2	oxadiazole; ring assembly
gentamicin b gentamicin B: RN given refers to gentamicin B; see also records for gentamicin A and gentamicin C	2.17	1
oligonucleotides [no description available]	3.17	1
tetracycline Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.. tetracycline : A broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria.	2.52	2
minocycline Minocycline: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.. minocycline : A tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5.	2.1	1
tigecycline [no description available]	2.1	1

Condition	Relationship Strength	Studies
Blood Poisoning [description not available]	2.01	1
E coli Infections [description not available]	2.01	1
Escherichia coli Infections Infections with bacteria of the species ESCHERICHIA COLI.	2.01	1
Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.	2.01	1
Genetic Diseases [description not available]	8.09	1
Genetic Diseases, Inborn Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.	3.09	1
Becker Muscular Dystrophy [description not available]	4.35	4
Muscular Dystrophy, Duchenne An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)	4.35	4
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	2.99	1
Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	2.01	1
Muscular Dystrophy, Animal MUSCULAR DYSTROPHY that occurs in VERTEBRATE animals.	2.01	1
Muscular Dystrophy [description not available]	3.35	2
Muscular Dystrophies A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.	3.35	2

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