Antibiotic, antiviral, antifungal, antitumor and insecticidal activity; insecticide; nematocide.
Potassium ionophore – Valinomycin is a potassium-specific ionophore that forms a stable complex with K⁺ ions, selectively transporting them across biological membranes. [1]

HepG2 viability is significantly suppressed by lipo-valinomycin (1-100 μM, 24 h) in a concentration-dependent manner[2].
HepG2 undergoes apoptosis (23%) and has its mitochondrial membrane potential degraded by lipo-valentinomycin (15 μM, 12 h)[2].

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Valinomycin exhibits broad-spectrum antibacterial activity against Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis. Minimum inhibitory concentrations (MICs) range from 0.02 μg/mL for Streptococcus pyogenes to 8 μg/mL for Clostridium sporogenes. It shows no activity against Gram-negative bacteria unless their outer membrane is compromised. [1]
Valinomycin displays antifungal activity against various fungi. MICs include 0.39-0.78 μg/disk for Candida albicans, 4 μg/mL for Botrytis cinerea and Magnaporthe grisea, and an IC₅₀ of 15.9 μg/mL for Phytophthora capsici. [1]
Valinomycin shows potent antiviral activity against multiple viruses. EC₅₀/IC₅₀ values include 0.85 μM for SARS-CoV, 24 nM for PRRSV, 5-84 nM for MERS-CoV, 78 nM for Zika virus, and values ranging from 41 to 971 nM for several other viruses (e.g., La Crosse virus, Coxsackievirus B3). [1]
Valinomycin demonstrates insecticidal and antiparasitic activity. LD₅₀ values are 0.02-0.03 μg for house flies (Musca domestica) and 0.19-0.5 μg for cockroaches (Periplaneta americana). LC₅₀ values are 2-3 μg/mL for mosquito larvae (Aedes aegypti) and 3 ppm for spider mites. IC₅₀ values are 5.3 ng/mL for Plasmodium falciparum and 0.0032 μM for Trypanosoma brucei brucei. [1]
Valinomycin exhibits antitumor activity against multiple human cancer cell lines. GI₅₀ values range from 0.19 to 1.9 ng/mL for panels of tumor cells (e.g., ovarian OVCAR-3, lung NCI-H460). It induces apoptosis through mitochondrial membrane potential loss, caspase-3 activation, and DNA fragmentation. [1]

In nude mice, lipo-valinomycin (1–40 μg/g, i.v., every two days for 16 days) inhibits the growth of HepG2 tumors[2].

Valinomycin was initially isolated as an antibiotic compound, showing the antibacterial activity against Mycobacterium tuberculosis. It was also the first natural compound recognized as an ionophore with antibiotic activity. Later, a diverse spectrum of biological activities of valinomycin was demonstrated that ranges from antifungal, antiviral, and insecticidal to antitumor efficacy. Recent studies even reported that valinomycin as a mitophagy activator also plays a positive role in the treatment of Parkinson’s disease and Alzheimer’s disease. Examples of such bioactivities are introduced in this section and representative dose-dependent activities are summarized in Table 1[1].

Valinomycin is a depsipeptide antibiotic which selectively translocates potassium across biologic membranes. This potassium ionophore was observed to inhibit phytohemagglutinin-stimulated blastogenesis and proliferation in human lymphocytes. The effect was not due to toxicity to the cells, nor appeared to be due to the effects of valinomycin as an uncoupler of oxidative phosphorylation. Furthermore, the inhibitory effect on phytohemagglutinin stimulated lymphocytes was prevented by increasing the potassium concentration of the external media. These results suggest that the interaction of mitogens with specific receptors at the cell membrane may involve mechanisms affecting cation fluxes and membrane potential. These ionic events may play a role in the transduction of membrane signals for lymphocyte stimulation[3].

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Antimicrobial activity was assessed using standard broth dilution or disk diffusion assays to determine Minimum Inhibitory Concentrations (MICs). [1]
Antiviral activity was evaluated using cell-based assays (e.g., viral titer reduction in Vero or MARC-145 cells) to determine half-maximal effective/inhibitory concentrations (EC₅₀/IC₅₀). [1]
Cytotoxicity and antitumor activity were assessed using cell viability assays (e.g., against various cancer cell lines) to determine half-maximal growth inhibition (GI₅₀) or inhibitory concentrations (IC₅₀). Apoptosis induction was evaluated by measuring markers such as mitochondrial membrane potential loss, caspase-3 activation, and DNA fragmentation. [1]
The review does not provide a step-by-step, detailed protocol for a specific cellular assay like Western blot or PCR in the context of valinomycin's mechanism of action. [1]

Nude mice using HepG2 as an animal model[2]
Quantity: 1, 2, 5, 10, 20, 40 μg/g
Administration: 16 daysof intravenous (i.v.) injections every two days
Result: Showed a strong inhibitory effect on tumor growth and did not cause weight loss while on treatment. because the majority of the tumor cells were in the apoptotic state, caused destructive tumor necrosis.

Interactions
Fructose-1,6-bisphosphate antagonizes potassium chloride-induced inhibition of rabbit myocardial contractility and valamicin-induced depolarization in vitro.

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Oral LD50 in rats: 4 mg/kg

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Adverse reactions:
Neurotoxins - Other central nervous system neurotoxins

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Interactions
Fructose-1,6-bisphosphate antagonizes potassium chloride-induced inhibition of rabbit myocardial contractility and valamicin-induced depolarization in vitro. ……

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Valamicin can induce apoptosis in various mammalian cell types (including human natural killer (NK) cells), indicating its potential cytotoxicity. [1]
The toxicity of the insects was quantified: the LD₅₀ value for the housefly (Musca domestica) was 0.02 μg for males and 0.03 μg for females; the LD₅₀ value for the American cockroach (Periplaneta americana) was 0.19 μg for males and 0.5 μg for females. [1]
This review points out that the overall cytotoxicity of valine currently limits its clinical application. [1]

[1]. The Nonribosomal Peptide Valinomycin: From Discovery to Bioactivity and Biosynthesis. Microorganisms. 2021，9(4):780.

[2]. RETRACTED: Liposomal valinomycin mediated cellular K+ leak promoting apoptosis of liver cancer cells. J Control Release. 2021，337:317-328.

[3]. A potassium ionophore (valinomycin) inhibits lymphocyte proliferation by its effects on the cell membrane. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3599-602.

lustrous crystalline solid. Used as an insecticide and nematicide. Not registered as an insecticide in the United States (EPA, 1998). Valinemycin is a twelve-membered cyclic condensate composed of three repeating D-α-hydroxyisovaleryl-D-valine-L-lactyl-L-valine units linked in sequence. It is an antibiotic found in various Streptomyces strains. It possesses antiviral, antibacterial, potassium ion carrier, and bacterial metabolite-related functions. It is a cyclic condensate and macrocyclic compound. A cyclic dodecapeptide ion carrier antibiotic produced by Streptomyces fulvissimus, associated with enniatin antibiotics. It consists of three L-valine, three D-α-hydroxyisovaleric acid, three D-valine, and three L-lactate units linked alternately to form a 36-membered ring. (Excerpt from Merck Index, 11th edition) Valinemycin is a potassium-selective ion carrier commonly used in biochemical research.
Valine has been reported to exist in Streptomyces tsusimaensis, Streptomyces levoris, and other organisms with relevant data.
Valine is a cyclic peptide isolated from Streptomyces fulvissimus. As a potassium-specific ion carrier, this fungal component causes loss of mitochondrial membrane potential, thereby initiating apoptosis. (NCI04)
A cyclic dodecapeptide ion carrier antibiotic produced by Streptomyces fulvissimus, associated with enniatin antibiotics. It consists of three alternating L-valine, three D-α-hydroxyisovaleric acid, three D-valine, and three L-lactate molecules forming a 36-membered ring. (Excerpt from Merck Index, 11th edition) Valine is a potassium-selective ion carrier commonly used in biochemical research.

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Valamicin is a nonribosomal peptide, specifically a 36-membered cyclic dodecapeptide, first isolated from Streptomyces fulvissimus in 1955. [1]
Its primary mechanism of action is as a potassium-selective ion carrier. It forms a hydrophobic complex with K⁺, promoting K⁺ transmembrane transport, thereby dissipating membrane potential and disrupting the cellular ion gradient, ultimately leading to cell death. A secondary mechanism of action involves inhibiting the elongation step of protein synthesis. [1]
Valamicin is considered a potential COVID-19 candidate drug due to its potent activity against coronaviruses such as SARS-CoV and MERS-CoV (IC₅₀ values in the nanomolar range) and its similarity to the SARS-CoV-2 genome. Molecular docking studies have shown that valamicin has a high binding energy to the SARS-CoV-2 protein. [1]
To reduce its toxicity, various strategies have been explored, such as liposome encapsulation and structural modification, to generate derivatives with lower toxicity (e.g., hydroxylated analogs). [1]

C54H90N6O18

1111.3218

1110.631

C, 74.35; H, 4.82; N, 11.82; O, 9.00

2001-95-8

3000706

White to off-white solid powder

1.1±0.1 g/cm3

1333.9±65.0 °C at 760 mmHg

186-190ºC

760.5±34.3 °C

0.0±0.3 mmHg at 25°C

1.449

-2.08

6

18

9

78

1910

12

O1C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])([H])[H])OC([C@@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])OC([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])([H])[H])OC([C@@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])OC([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@]([H])(C([H])([H])[H])OC(C([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@@]1([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O

FCFNRCROJUBPLU-DNDCDFAISA-N

InChI=1S/C54H90N6O18/c1-22(2)34-49(67)73-31(19)43(61)55-38(26(9)10)53(71)77-41(29(15)16)47(65)59-36(24(5)6)51(69)75-33(21)45(63)57-39(27(11)12)54(72)78-42(30(17)18)48(66)60-35(23(3)4)50(68)74-32(20)44(62)56-37(25(7)8)52(70)76-40(28(13)14)46(64)58-34/h22-42H,1-21H3,(H,55,61)(H,56,62)(H,57,63)(H,58,64)(H,59,65)(H,60,66)/t31-,32-,33-,34+,35+,36+,37-,38-,39-,40+,41+,42+/m0/s1

(3R,6R,9S,12S,15R,18R,21S,24S,27R,30R,33S,36S)-3,6,9,15,18,21,27,30,33-Nonaisopropyl-12,24,36-trimethyl-1,7,13,19,25,31-hexaoxa-4,10,16,22,28,34-hexaazacyclohexatriacontane-2,5,8,11,14,17,20,23,26,29, 32,35-dodecone

NSC 122023; NSC-122023; valinomycin; 2001-95-8; Potassium ionophore I; Valinomicin; valino; Antibiotic N-329 B; CHEBI:28545; N561YS75MN; NSC122023

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~50 mg/mL (~44.99 mM )
DMSO : ~25 mg/mL (~22.50 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (2.25 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.5 mg/mL (2.25 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well.

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Solubility in Formulation 5: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (2.25 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)