Page last updated: 2024-11-06

nigericin

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Description

Nigericin is a naturally occurring ionophore antibiotic produced by Streptomyces hygroscopicus. It is a carboxylic acid polyether with a cyclic structure that facilitates the exchange of potassium ions (K+) for protons (H+) across cell membranes. Nigericin has been studied extensively for its effects on cellular processes, particularly its ability to disrupt mitochondrial function. The compound can cause mitochondrial membrane depolarization by transporting potassium ions out of the mitochondria, leading to the dissipation of the proton gradient necessary for ATP synthesis. This effect can lead to cell death. Nigericin is also known to inhibit the activity of the Na+/K+ ATPase, a key enzyme in maintaining cellular ion homeostasis. The compound's ability to disrupt cellular ion transport has made it a valuable tool in research studies investigating various aspects of cell physiology, such as mitochondrial function, ion channel activity, and signal transduction. Its potential applications in medicine include its use as an antifungal agent and its investigation as a potential therapeutic for cancer treatment. The synthesis of Nigericin is a complex process that involves multiple steps, including the use of protecting groups to selectively modify functional groups within the molecule.'

Nigericin: A polyether antibiotic which affects ion transport and ATPase activity in mitochondria. It is produced by Streptomyces hygroscopicus. (From Merck Index, 11th ed) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

nigericin : A polyether antibiotic which affects ion transport and ATPase activity in mitochondria. It is produced by Streptomyces hygroscopicus. [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 CID34230
CHEMBL ID405862
CHEBI ID7569
SCHEMBL ID149611
MeSH IDM0014855

Synonyms (36)

Synonym
brn 1696755
helixin c
x-464
nsc292567 ,
BSPBIO_001599
(2r)-2-((3s)-6-{[2-((5s)-5-{(3s)-5-[(3s,5r,6r)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethylperhydro-2h-pyran-2-yl]-3-methyloxolan-2-yl}-5-methyloxolan-2-yl)(2s,4r,9r,10r)-9-methoxy-2,4,10-trimethyl-1,6-dioxaspiro[4.5]dec-7-yl]methyl}-3-methylperhydro-2h-pyran
azalomycin m
helix c
antibiotic k 178
(2r)-2-[(2r,3s,6r)-6-[[(1r,3s,5r,6r,7r,9r)-3-[(2r,5s)-5-[(2r,3s,5r)-5-[(2s,3s,5r,6r)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyl-tetrahydropyran-2-yl]-3-methyl-tetrahydrofuran-2-yl]-5-methyl-tetrahydrofuran-2-yl]-7-methoxy-1,3,6-trimethyl-4,10-dioxaspiro[4.5
antibiotic x-464
nigericin
28380-24-7
NCGC00163412-02
(2r)-2-[(2r,3s,6r)-6-{[(2s,4r,5r,7r,9r,10r)-2-{(2s,2'r,3's,5r,5'r)-5'-[(2s,3s,5r,6r)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyltetrahydro-2h-pyran-2-yl]-2,3'-dimethyloctahydro-2,2'-bifuran-5-yl}-9-methoxy-2,4,10-trimethyl-1,6-dioxaspiro[4.5]dec-7-yl]methyl}
HMS1989P21
CHEMBL405862
CHEBI:7569 ,
HMS1791P21
rru6gy95is ,
unii-rru6gy95is
nigericin [mi]
CA-421
SCHEMBL149611
HMS3402P21
DTXSID9041079
SR-05000002332-2
sr-05000002332
antibiotic k178;antibiotic x464
DB14056
Q7033077
CS-0091495
HY-127019
(2r)-2-[(2r,3s,6r)-6-[[(2s,4r,5r,6r,7r,9r)-2-[(2r,5s)-5-[(2r,3s,5r)-5-[(2s,3s,5r,6r)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-7-methoxy-2,4,6-trimethyl-1,10-dioxaspiro[4.5]decan-9-yl]methyl]-3-methyloxan
2h-pyran-2-acetic acid, tetrahydro-6-[[(2s,4r,5r,7r,9r,10r)-9-methoxy-2,4,10-trimethyl-2-[(2s,2'r,3's,5r,5'r)-octahydro-2,3'-dimethyl-5'-[(2s,3s,5r,6r)-tetrahydro-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyl-2h-pyran-2-yl][2,2'-bifuran]-5-yl]-1,6-dioxaspiro[4
AKOS040742303

Research Excerpts

Overview

Nigericin is an ionophore which permits the influx of H+ ions into cells down a concentration gradient, thus reducing intracellular pH (pHi) Nigericin may prove to be a novel therapeutic strategy that is effective in patients with metastatic EOC.

ExcerptReferenceRelevance
"Nigericin may prove to be a novel therapeutic strategy that is effective in patients with metastatic EOC."( Nigericin Inhibits Epithelial Ovarian Cancer Metastasis by Suppressing the Cell Cycle and Epithelial-Mesenchymal Transition.
Cui, X; Dong, T; Gao, J; Huang, W; Pan, W; Wang, W; Yao, S; Zhang, S; Zhao, Y, 2017
)
2.62
"Nigericin is an ionophore which permits the influx of H+ ions into cells down a concentration gradient, thus reducing intracellular pH (pHi) when extracellular pH is low. "( Reduction of tumour intracellular pH and enhancement of melphalan cytotoxicity by the ionophore Nigericin.
Newell, K; Sansom, JM; Stratford, IJ; Tannock, IF; Wood, PJ, 1995
)
1.95
"Nigericin is an ionophore commonly used at the end of experiments to calibrate intracellularly trapped pH-sensitive dyes. "( Effect of trace levels of nigericin on intracellular pH and acid-base transport in rat renal mesangial cells.
Bashi, E; Bevensee, MO; Boron, WF, 1999
)
2.05
"Nigericin is a monocarboxylic polyether molecule described as a mobile K+ ionophore unable to transport Li+ and Cs+ across natural or artificial membranes. "( Nigericin forms highly stable complexes with lithium and cesium.
Alva, R; Arzt, E; Cerbón, J; Estrada, S; Lugo, JA; Rivera, BE; Toro, M, 1992
)
3.17

Effects

Nigericin has only weak activity on its own but it also enhances rapamycin action. Nigericin induces apoptosis and pyroptosis in mammals.

ExcerptReferenceRelevance
"Nigericin has been reported to induce apoptosis and pyroptosis in mammalian models. "( Nigericin treatment activates endoplasmic reticulum apoptosis pathway in goldfish kidney leukocytes.
Gouife, M; Huang, K; Jiang, J; Jin, S; Li, X; Ma, R; Nawaz, M; Xie, J; Yue, X; Zhu, S, 2023
)
3.8
"Nigericin has only weak activity on its own but it also enhances rapamycin action."( Enhancement of the antifungal activity of rapamycin by the coproduced elaiophylin and nigericin.
Demain, AL; Fang, A; Wong, GK, 2000
)
1.25

Actions

Nigericin can inhibit cell growth of osteosarcoma cells. In addition to S-phase cycle arrest, the nigeric in induces apoptosis. Nigericin induced an increase in the hydrolysis/exchange ratio from 2.7 to 130.

ExcerptReferenceRelevance
"Nigericin can inhibit cell growth of osteosarcoma cells, in addition to S-phase cycle arrest, the nigericin induces apoptosis."( Nigericin exerts anticancer effects through inhibition of the SRC/STAT3/BCL-2 in osteosarcoma.
Cai, L; Deng, Z; Fang, J; Lv, M; Xie, J; Xie, Y; Yang, M; Yang, Z, 2022
)
2.89
"The nigericin-induced increase in [Ca(2+)]i and annexin V binding was again significantly blunted but not abolished by the Na(+)/H(+) exchanger inhibitor cariporide (10 μM)."( Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin.
Abbès, S; Bissinger, R; Bouguerra, G; Lang, F; Malik, A; Singh, Y; Zhou, Y, 2016
)
1.15
"Nigericin did not inhibit D-xylose taxis in either potassium or sodium phosphate buffer."( Chemotaxis of Spirochaeta aurantia: involvement of membrane potential in chemosensory signal transduction.
Goulbourne, EA; Greenberg, EP, 1981
)
0.98
"Nigericin induced an increase in the hydrolysis/exchange ratio from 2.7 to 130, whereas in the presence of valinomycin, this ratio increased from 2.7 to 21."( Coupling of ATP hydrolysis to phosphate uptake in Rhodospirillum rubrum chromatophores under the influence of Ca2+ and Mg2+.
Dreyfus, G; Martins, OB; Montero-Lomelí, M, 1989
)
1

Treatment

Nigericin treatment of cells showed that the recovery in pHi was Na+-dependent and followed Michaelis-Menten kinetics. Nigericin-treated cells had more extensive vacuolization of the cytoplasm and the localization of the enzyme was more diffuse within these vacuoles.

ExcerptReferenceRelevance
"Nigericin treatment of cells showed that the recovery in pHi was Na+-dependent and followed Michaelis-Menten kinetics."( Freeze-dried rehydrated human blood platelets regulate intracellular pH.
Crowe, JH; Tablin, F; Tang, M; Wolkers, WF, 2006
)
1.06
"Nigericin-treated cells had more extensive vacuolization of the cytoplasm and the localization of the enzyme was more diffuse within these vacuoles."( Immunocytochemical localization of beta-hexosaminidase and electron-microscopic characterization of human fibroblasts following treatment with monensin and nigericin.
Vladutiu, GD, 1984
)
1.19
"In nigericin-pretreated cells, PMA caused a rapid rise in pHi without changing the [Ca2+]i."( Mechanisms of activation of Na+/H+ exchange in human osteoblast-like SaOS-2 cells.
Graham, CS; Tashjian, AH, 1992
)
0.8
"Treatment of nigericin or ML385 counteracted the role of Hyd in ameliorating pyroptosis of AMs and CPB-induced ALI."( HYDROMORPHONE MITIGATES CARDIOPULMONARY BYPASS-INDUCED ACUTE LUNG INJURY BY REPRESSING PYROPTOSIS OF ALVEOLAR MACROPHAGES.
An, Z; Li, J; Qi, J; Zhang, J, 2023
)
1.26
"Treatment with nigericin during influenza infection augmented IL-1β production, increased caspase-1 activity, and decreased morbidity and mortality in elderly mice."( Impaired NLRP3 inflammasome function in elderly mice during influenza infection is rescued by treatment with nigericin.
Harrod, KS; Jaramillo, RJ; Shirali, AC; Stout-Delgado, HW; Vaughan, SE, 2012
)
0.93
"Treatment with nigericin also depleted intracellular K+ and decreased ATP-induced toxicity."( Involvement of intracellular Ca2+ and K+ in dissipation of the mitochondrial membrane potential and cell death induced by extracellular ATP in hepatocytes.
de Bont, HJ; Mulder, GJ; Nagelkerke, JF; van de Water, B; Zoeteweij, JP, 1992
)
0.62

Toxicity

ExcerptReferenceRelevance
" The raising of the intracellular pH of ciliates by this antibiotic may be linked to its toxic action and its iontransport mechanism in Tetrahymena."( Epinigericin toxicity towards Tetrahymena pyriformis GL; changes in cell volume and intracellular pH.
Bamdad, M; David, L; Grolière, CA, 1995
)
0.91
"Idiopathic and toxic pulmonary fibrosis are severe diseases starting classically in the subpleural area of the lung."( Pleural inhibition of the caspase-1/IL-1β pathway diminishes profibrotic lung toxicity of bleomycin.
Bellaye, PS; Beltramo, G; Bonniaud, P; Boutanquoi, PM; Burgy, O; Causse, S; Garrido, C; Goirand, F; Wettstein, G, 2016
)
0.43

Bioavailability

ExcerptReferenceRelevance
" Complexing shikonin with β-lactoglobulin reduced its toxicity while preserving the inhibitory effect on NLRP3 inflammasome activation, suggesting that shikonin with improved bioavailability might be interesting for therapeutic applications in inflammasome-mediated conditions."( Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1.
Hafner-Bratkovič, I; Sušjan, P; Zorman, J, 2016
)
0.43

Dosage Studied

Nigericin affects primarily the shoulder of the PDT dose-response curve. Nigericin reduces the surviving fraction from 0.1% to 0.2%.

ExcerptRelevanceReference
" The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can be enhanced by using acidified dosing solutions."( Different pH dependency of mitomycin C activity in monolayer and three-dimensional cultures.
Au, JL; Schmittgen, T; Yen, WC, 1996
)
0.29
" The time lag for pHi to equilibrate with pHe in the multilayer systems and the instability of MMC at low pHe imply that the efficacy of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing solution."( Different pH dependency of mitomycin C activity in monolayer and three-dimensional cultures.
Au, JL; Schmittgen, T; Yen, WC, 1996
)
0.29
"Oral dosing with DMP 777 caused a rapid increase in serum gastrin levels and severe hypochlorhydria."( Reversible drug-induced oxyntic atrophy in rats.
Barnes, TB; Car, BD; Coffey, RJ; Goldenring, JR; Haley, PJ; Meunier, PC; Ray, GS, 2000
)
0.31
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
antimicrobial agentA substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
antibacterial agentA substance (or active part thereof) that kills or slows the growth of bacteria.
potassium ionophoreAny ionophore capable of transportation of potassium ions across membranes.
bacterial metaboliteAny prokaryotic metabolite produced during a metabolic reaction in bacteria.
[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 (1)

ClassDescription
polycyclic ether
[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]

Bioassays (27)

Assay IDTitleYearJournalArticle
AID519608Selectivity index, ratio of TC50 for hepatocytes to IC50 for Plasmodium yoelii 2008Antimicrobial agents and chemotherapy, Apr, Volume: 52, Issue:4
New active drugs against liver stages of Plasmodium predicted by molecular topology.
AID324426Increase in light chain 3-GFP+ autophagosome vesicle number per cell in human H4 cells at 3.4 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324478Increase in light chain 3-GFP+ autophagosome vesicle area per cell in human H4 cells at 3.4 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID519606Antimicrobial activity against Plasmodium yoelii 265 liver infected in mammalian hepatocytes after 48 hrs2008Antimicrobial agents and chemotherapy, Apr, Volume: 52, Issue:4
New active drugs against liver stages of Plasmodium predicted by molecular topology.
AID332869Herbicidal activity against Lepidium sativum assessed as occurrence of browning and tissue necrosis
AID519609Antimicrobial activity against Plasmodium falciparum NF54 schizonts in mammalian hepatocytes after 96 hrs2008Antimicrobial agents and chemotherapy, Apr, Volume: 52, Issue:4
New active drugs against liver stages of Plasmodium predicted by molecular topology.
AID554736Inhibition of Candida krusei ABC1 expressed in Saccharomyces cerevisiae isolate ADdelta at 8 nM2009Antimicrobial agents and chemotherapy, Feb, Volume: 53, Issue:2
Abc1p is a multidrug efflux transporter that tips the balance in favor of innate azole resistance in Candida krusei.
AID1601781Antimalarial activity against Plasmodium vinckei petteri infected in IOPS OF1 mouse assessed as reduction in parasitemia administered once daily via sc for 4 days2019European journal of medicinal chemistry, Mar-15, Volume: 166Anti-parasitic activity of polyether ionophores.
AID324574Increase in FYVE-RFP+ vesicle intensity per cell in human H4 cells after 8 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324572Increase in FYVE-RFP+ vesicle intensity per cell in human H4 cells after 2 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID332868Herbicidal activity against Lepidium sativum assessed as inhibition of radicle growth of seed at 3 to 4 ppm after 69 to 75 hrs in dark
AID324585Increase in long-lived protein degradation in human H4 cells after 24 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID332870Herbicidal activity against Lepidium sativum assessed as inhibition of radicle growth of seeds at 1 to 2 ppm after 69 to 75 hrs in dark
AID538370Cytotoxicity against human LNCAP cells at 100 pM to 1 uM2010Journal of medicinal chemistry, Nov-11, Volume: 53, Issue:21
Synthesis and biological analysis of prostate-specific membrane antigen-targeted anticancer prodrugs.
AID332872Toxicity in ip dosed mouse
AID324573Increase in FYVE-RFP+ vesicle intensity per cell in human H4 cells after 4 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID1138427Induction of collapse in deltapH in Mycobacterium smegmatis inverted membrane vesicles at 30 to 150 uM by 31P NMR spectroscopy2014Journal of medicinal chemistry, Apr-10, Volume: 57, Issue:7
Multitarget drug discovery for tuberculosis and other infectious diseases.
AID756032Induction of acidocalcisomes alkalinization in Leishmania (V.) braziliensis MHOM/CO/87/UA301 at 1 uM up to 1400 seconds using acridine orange staining2013Bioorganic & medicinal chemistry, Jul-15, Volume: 21, Issue:14
Anti-leishmanial evaluation of C2-aryl quinolines: mechanistic insight on bioenergetics and sterol biosynthetic pathway of Leishmania braziliensis.
AID519607Cytotoxicity against Hepatocyte cells assessed as cell viability by MTT assay2008Antimicrobial agents and chemotherapy, Apr, Volume: 52, Issue:4
New active drugs against liver stages of Plasmodium predicted by molecular topology.
AID397590Antiviral activity against HIV1 RF in human H9 cells assessed as inhibition of virus-induced cytopathic effect by formazan-based conventional colorimetric technique2001Journal of natural products, Feb, Volume: 64, Issue:2
Natural product-based anti-HIV drug discovery and development facilitated by the NCI developmental therapeutics program.
AID397757Cytotoxicity against human H9 cells2001Journal of natural products, Feb, Volume: 64, Issue:2
Natural product-based anti-HIV drug discovery and development facilitated by the NCI developmental therapeutics program.
AID324582Increase in long-lived protein degradation in human H4 cells after 1 hr relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324583Increase in long-lived protein degradation in human H4 cells after 2 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324374Induction of light chain 3-GFP level in human H4 cells at 3.4 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324530Increase in light chain 3-GFP+ autophagosome vesicle intensity per cell in human H4 cells at 3.4 uM after 24 hrs by high throughput fluorescence microscopy relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID324584Increase in long-lived protein degradation in human H4 cells after 4 hrs relative to control2007Proceedings of the National Academy of Sciences of the United States of America, Nov-27, Volume: 104, Issue:48
Small molecule regulators of autophagy identified by an image-based high-throughput screen.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,216)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990470 (38.65)18.7374
1990's364 (29.93)18.2507
2000's147 (12.09)29.6817
2010's157 (12.91)24.3611
2020's78 (6.41)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 48.91

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index48.91 (24.57)
Research Supply Index7.13 (2.92)
Research Growth Index4.54 (4.65)
Search Engine Demand Index81.07 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (48.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (0.24%)5.53%
Reviews12 (0.97%)6.00%
Case Studies1 (0.08%)4.05%
Observational0 (0.00%)0.25%
Other1,226 (98.71%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]