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Valinomycin (formerly known a NSC 122023) is a novel and potent cyclic depsipeptide antibiotic originally isolated from Streptomyces fulvissimus, it acts as a potassium selective ionophore. Valinomycin inhibits lymphocyte proliferation by its effects on the cell membrane, and induces apoptosis in CHO cells. Valinomycin is used as an insecticide and nematocide.
Physicochemical Properties
| Molecular Formula | C54H90N6O18 |
| Molecular Weight | 1111.3218 |
| Exact Mass | 1110.631 |
| Elemental Analysis | C, 74.35; H, 4.82; N, 11.82; O, 9.00 |
| CAS # | 2001-95-8 |
| PubChem CID | 3000706 |
| Appearance | White to off-white solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 1333.9±65.0 °C at 760 mmHg |
| Melting Point | 186-190ºC |
| Flash Point | 760.5±34.3 °C |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C |
| Index of Refraction | 1.449 |
| LogP | -2.08 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 18 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 78 |
| Complexity | 1910 |
| Defined Atom Stereocenter Count | 12 |
| SMILES | 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 |
| InChi Key | FCFNRCROJUBPLU-DNDCDFAISA-N |
| InChi Code | 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 |
| Chemical Name | (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 |
| Synonyms | NSC 122023; NSC-122023; valinomycin; 2001-95-8; Potassium ionophore I; Valinomicin; valino; Antibiotic N-329 B; CHEBI:28545; N561YS75MN; NSC122023 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
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. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Antibiotic, antiviral, antifungal, antitumor and insecticidal activity; insecticide; nematocide. |
| ln Vitro |
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]. |
| ln Vivo | In nude mice, lipo-valinomycin (1–40 μg/g, i.v., every two days for 16 days) inhibits the growth of HepG2 tumors[2]. |
| Enzyme Assay | 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]. |
| Cell Assay | 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]. |
| Animal Protocol |
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. |
| Toxicity/Toxicokinetics |
Interactions
Fructose-1,6-disphosphate counteracts the inhibition of contractile strength of rabbit cardiac muscle induced by potassium chloride in vitro and valinomycin induced depolarization. rat LD50 oral 4 mg/kg Adverse Effects: Neurotoxin - Other CNS neurotoxin Interactions Fructose-1,6-disphosphate counteracts the inhibition of contractile strength of rabbit cardiac muscle induced by potassium chloride in vitro and valinomycin induced depolarization. ... |
| References |
[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. |
| Additional Infomation |
Shiny crystalline solid. Used as an insecticide and nematocide. Not registered as a pesticide in the U.S. (EPA, 1998) Valinomycin is a twelve-membered cyclodepsipeptide composed of three repeating D-alpha-hydroxyisovaleryl-D-valyl-L-lactoyl-L-valyl units joined in sequence. An antibiotic found in several Streptomyces strains. It has a role as an antiviral agent, an antimicrobial agent, a potassium ionophore and a bacterial metabolite. It is a cyclodepsipeptide and a macrocycle. A cyclododecadepsipeptide ionophore antibiotic produced by Streptomyces fulvissimus and related to the enniatins. It is composed of 3 moles each of L-valine, D-alpha-hydroxyisovaleric acid, D-valine, and L-lactic acid linked alternately to form a 36-membered ring. (From Merck Index, 11th ed) Valinomycin is a potassium selective ionophore and is commonly used as a tool in biochemical studies. Valinomicin has been reported in Streptomyces tsusimaensis, Streptomyces levoris, and other organisms with data available. Valinomycin is a cyclic depsipeptide isolated from the bacterium Streptomyces fulvissimus. As a potassium-specific ionophore, mould element causes loss of mitochondrial membrane potential, thereby initiating cellular apoptosis. (NCI04) A cyclododecadepsipeptide ionophore antibiotic produced by Streptomyces fulvissimus and related to the enniatins. It is composed of 3 moles each of L-valine, D-alpha-hydroxyisovaleric acid, D-valine, and L-lactic acid linked alternately to form a 36-membered ring. (From Merck Index, 11th ed) Valinomycin is a potassium selective ionophore and is commonly used as a tool in biochemical studies. |
Solubility Data
| Solubility (In Vitro) |
Ethanol : ~50 mg/mL (~44.99 mM ) DMSO : ~25 mg/mL (~22.50 mM) |
| Solubility (In Vivo) |
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. 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. 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. 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. Solubility in Formulation 5: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (2.25 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8998 mL | 4.4992 mL | 8.9983 mL | |
| 5 mM | 0.1800 mL | 0.8998 mL | 1.7997 mL | |
| 10 mM | 0.0900 mL | 0.4499 mL | 0.8998 mL |