Antibiotic

Streptomyces cinnamonensis produces the antibiotic monensin sodium salt, which causes cell death. Cells treated by default showed 2.5% sterility; 48 hours of treatment with 1 μM monensin sodium salt led to 4.5% cell death; in contrast, 48 hours of treatment with 5 μM monensin sodium salt produced a higher percentage of cell disinfection (16.4%). When monensin sodium salt was depleted at 1 or 5 μM for 24 hours, and then treated at 10 μM for 24 hours, there was a notable rise in cell engraftment events as compared to when monensin sodium salt or erlotinib was treated (14.6% and 38.7%, respectively). The combination of 10 μM erlotinib and 5 μM sodium monensin salt exhibited the largest proportion of cellular artifacts (38.7%) [1].

Monensin sodium-treated Apc+/Min mice showed a substantial (P=0.0144) decrease in the mean size of lesions when compared to control animals (mean 0.199 mm2 and 0.299 mm2). However, there was no significant change in the number of tumors. One animal's estimated total tumor area decreased (mean 10.16 mm2 vs. 16.46 mm2; P=0.0125) among those receiving monensin sodium. The amount of South African cells and cells expressing the p21 cell cycle in the tumor growth surface area increased after treatment with monensin sodium salt. In healthy sections of the mucosa, there were no alterations in cell proliferation, necrosis, or tissue structure following exposure to monensin sodium salt [2].

Targeting the EGFR, with inhibitors such as erlotinib, represents a promising therapeutic option in advanced head and neck squamous cell carcinomas (HNSCC). However, they lack significant efficacy as single agents. Recently, we identified the ability of statins to induce synergistic cytotoxicity in HNSCC cells through targeting the activation and trafficking of the EGFR. However, in a phase I trial of rosuvastatin and erlotinib, statin-induced muscle pathology limited the usefulness of this approach. To overcome these toxicity limitations, we sought to uncover other potential combinations using a 1,200 compound screen of FDA-approved drugs. We identified monensin, a coccidial antibiotic, as synergistically enhancing the cytotoxicity of erlotinib in two cell line models of HNSCC, SCC9 and SCC25. Monensin treatment mimicked the inhibitory effects of statins on EGFR activation and downstream signaling. RNA-seq analysis of monensin-treated SCC25 cells demonstrated a wide array of cholesterol and lipid synthesis genes upregulated by this treatment similar to statin treatment. However, this pattern was not recapitulated in SCC9 cells as monensin specifically induced the expression of activation of transcription factor (ATF) 3, a key regulator of statin-induced apoptosis. This differential response was also demonstrated in monensin-treated ex vivo surgical tissues in which HMG-CoA reductase expression and ATF3 were either not induced, induced singly, or both induced together in a cohort of 10 patient samples, including four HNSCC. These results suggest the potential clinical utility of combining monensin with erlotinib in patients with HNSCC[1].

The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/β-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with β-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or β-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of β-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling[2].

Absorption, Distribution and Excretion
The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 hr, volume of distribution of 4.11 l/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 hr after intracrop dosage with an absorption half-life of 0.27 hr and an elimination half life of 2.11 hr. The systemic bioavailability was 65.1% after intracrop administration. Serum protein-binding tendency of monensin calculated in vitro was 22.8%. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin premix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 hr after oral administration. The highest concentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 hr after the last oral dose. No monensin residues could be detected in tissues after 48 hr, except in liver which cleared completely by 72 hr.
Six chickens were exposed to (3)H-monensin sodium at 121 mg/kg in the diet for 2 days. Only 52-73% of the radioactivity was recovered; of this, 97% was found in the faeces. The reason for poor radioactivity balance was unknown. /Monensin sodium/
Broiler chickens were administered (14)C-monensin sodium at a concentration of 120 mg/kg in the diet for 4 days (two males, three females) or 6 days (three males, three females). Six hours after withdrawal from the treated feed, radioactivity was detected in the liver, kidney, fat and skin, with the highest level detected in the liver (0.5 mg/kg liver). No radioactivity was detected in the muscle tissue. /Monensin sodium/
Ten White Leghorn roosters and two White Leghorn hens were exposed orally to a single dose of (14)C-monensin in a gelatine capsule (dose range: 2.6-100 mg). Some birds were colostomized, whereas others had bile cannulae inserted. Absorption in the chickens ranged from 11% to 31% of the ingested (14)C-monensin. The primary route of excretion was in the faeces, with a small proportion excreted in the urine and by respiration.
For more Absorption, Distribution and Excretion (Complete) data for MONENSIN (21 total), please visit the HSDB record page.

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Metabolism / Metabolites
The oxidative metabolism of monensin, an ionophore antibiotic extensively used in veterinary practice as a coccidiostat and a growth promoter, was studied in hepatic microsomal preparations from horses, pigs, broiler chicks, cattle and rats. As assayed by the measurement of the amount of the released formaldehyde, the rate of monensin O-demethylation was nearly of the same order of magnitude in all species, but total monensin metabolism, which was estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatography (HPLC) method, was highest in cattle, intermediate in rats, chicks and pigs, and lowest in horses. When expressed as turnover number (nmol of metabolized monensin/min nmol cytochrome P450-1), the catalytic efficiency (chick >> cattle >> pig approximately rat > horse) was found to correlate inversely with the well known interspecies differences in the susceptibility to the toxic effects of the ionophore, which is characterized by an oral LD50 of 2-3 mg/kg bodyweight (bw) in horses, 50-80 mg/kg bw in cattle and 200 mg/kg bw in chicks. Chick and cattle microsomes also displayed both the highest catalytic efficiency toward two P450 3A dependent substrates (erythromycin and triacetyloleandomycin) and the highest immunodetectable levels of proteins cross-reacting with anti rat P450 3A1/2. ...
The O-demethylation of monensin is greater in microsomes from phenobarbital-treated rats than in untreated rats and is dependent on reduced nicotinamide adenine dinucleotide phosphate (NADPH), suggesting that monensin is a cytochrome P450 (CYP) enzyme substrate. The oxidative metabolism of monensin appears to occur at least in part by CYP3A, since treatment of rat hepatic microsomes with chemical inducers of CYP3A significantly increased monensin O-demethylation. It has been speculated that competition between monensin and other CYP3A substrates may explain accidental poisonings that have occurred in several domestic species following coadministration of monensin and other chemotherapeutic agents, since monensin metabolism is significantly decreased in the presence of other CYP3A substrates in rats.
Monensin metabolites result mainly from O-demethylation at the methoxylic group and/or hydroxylation at several places on the ionophore backbone. ... Although it is difficult to obtain sufficient monensin metabolites to test activity, four metabolites generated by rat liver microsomes, including a by-product of monensin production (O-desmethylmonensin), have been tested and have at least 10- to 20-fold less antibacterial, anticoccidial, cytotoxic, cardiotonic and ionophoric activity than the parent compound, indicating that metabolism eliminates most of the biological activity of monensin.
Monensin is extensively metabolized in the liver, producing more than 50 different metabolites that have been detected in the liver, bile and faeces of chickens, cattle, rats, pigs, dogs, turkeys, sheep and horses. In most species (chickens, rats, dogs, turkeys and pigs), less than 10% of monensin is excreted as the parent compound, whereas a study in calves indicated that 50-68% of the (14)C identified in the feces was unmetabolized monensin. This difference in amount of metabolized monensin may have been a result of differences in absorption of the molecule in different species. Total microsomal monensin metabolism, estimated by measuring the rate of substrate disappearance by a high-performance liquid chromatographic (HPLC) analytical method, is highest in cattle, intermediate in rats, chickens and pigs, and lowest in horses. The pattern of metabolites is qualitatively similar between laboratory and non-laboratory animal species, although quantitative differences exist. No single metabolite dominates the metabolic profile.
The metabolism of monensin sodium in human liver microsomes has been compared with metabolism in the microsomes of horses and dogs. A pooled human microsomal sample from multiple donors (male and female, Caucasian, Hispanic and African American, 15-66 years old), pooled dog microsome sample and equine microsomes from a single donor were incubated with 0.5, 1 and 10 ug monensin/mL in the presence or absence of NADPH. The metabolite profiles were examined at 0, 5, 10, 20, 40 and 60 min by liquid chromatography/mass spectrometry (LC-MS) analysis. Monensin was metabolized by first-order kinetics in all species, and metabolism was extensive (93-99% by 60 min). The turnover of monensin in humans was similar to that in dogs, whereas the turnover in horses was only 10% of that in dogs and humans.

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Biological Half-Life
The pharmacokinetics of monensin, including half-life, apparent volume of distribution, total body clearance, systemic bioavailability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 hr ... .The highest serum concentrations of monensin were reached 0.5 hr after intracrop dosage with an absorption half-life of 0.27 hr and an elimination half life of 2.11 hr. ...

Toxicity Summary
IDENTIFICATION AND USE: Monensin is a polyether carboxylic ionophore antibiotic. Monensin is a mixture of four analogues, A, B, C and D, with monensin A being the major component (98%). Depending on the method of purification, monensin can exist in mycelial, crystalline and recrystallized forms. It is used for the treatment of coccidiosis in poultry (chickens, turkeys and quail) and ruminants (cattle, sheep and goats). Monensin is also used to control ketosis and bloat in cattle and as a growth promoter feed additive in cattle and sheep. Monensin is mainly effective against Gram-positive bacteria. HUMAN EXPOSURE AND TOXICITY: 17 year-old boy who developed myoglobinuria, renal failure and death 11 days after ingesting sodium monensin. In another case, a patient took a dose of monensin three times higher than a dose considered lethal for cattle and developed a clinical picture similar to that reported in veterinary medicine. There was an early and extremely severe rhabdomyolysis followed by acute renal failure, heart failure, and death. The main changes observed at autopsy were extensive skeletal muscle necrosis, complement deposition at the myocardial level, pulmonary edema, & acute tubular damage. ANIMAL STUDIES: Acute toxicity was examined in mature rhesus monkeys. Pairs of monkeys were exposed to a single dose of 20, 40 or 60 mg monensin/kg bw by gavage and were monitored for 7 days. All animals survived and developed diarrhea within 24 hr after dosing. Adult goats were administered sodium monensin, 13.5 mg kg (-1), daily for five consecutive days via gastric gavage. Monensin exposure caused diarrhea, tachycardia and reduction in ruminal movements and body temperature. In an inhalational exposure study, rats were exposed to either normal air or air containing particulate mycelial monensin sodium at a mean concentration of 79 mg/cu m for 2 weeks (1 hr/day, 5 days/week). Nine of 10 treated females became anorexic and lost weight during the 2nd week of the study. Slight focal myositis of the skeletal muscle was seen in two males and two females but none of the controls. Multifocal myocardial changes were observed in male rats treated with monensin. In a subchronic study, male and female mice were fed diets containing 0, 37.5, 75, 150 or 300 mg mycelial monensin sodium/kg for 3 months. A dose-dependent decrease in body weight gain occurred in all dose groups. At the end of the study, the decrease ranged from 27% and 21% in the lowest dose group in females and males, respectively, to 99% in the highest dose group in both sexes. In a chronic toxicity study, male and female rats were maintained on a diet containing 25, 56 or 125 mg crystalline monensin sodium/kg, whereas control rats received a normal diet for 2 years. Body weight and weight gain were significantly decreased in animals receiving 125 mg monensin/kg in their diet and were transiently decreased during the first 4 months in rats in the middle dose group. Benign and malignant neoplasms were observed in treated and untreated animals, with no association between monensin administration and neoplasm type or severity. Monensin is toxic in horses. Clinical signs were tachycardia and cardiac arrythmia, groaning, incoordination, sudoresis, recumbency, and paddling movements with the limbs before death. Main necropsy findings were in the skeletal muscles and myocardium. The effects of exposure to monensin during development were studied in rats. Groups of female rats received monensin at concentrations of 0, 100 or 300 mg/kg until premating weights achieved 185 g and during pregnancy and lactation. Female body weight was significantly decreased in the highest dose group after 8 days of treatment. The body weights of male and female pups in the highest dose group were reduced from postnatal day 10 until postnatal day 21. Male offspring in the low dose group showed body weight reduction only on postnatal day 21. No external signs of malformation were detected in the pups. A study was also undertaken to explore the effects of monensin, a potent Golgi disturbing agent on male fertility. Male rats were administered monensin at the dose levels of 2.5, 5, and 10 mg/kg b wt. Animals were sacrificed after 67 days of the treatment. The findings from electron microscopy such as membrane disruption, swelling and disintegration of Golgi apparatus strongly suggest the interference of monensin with the functioning of Golgi apparatus in the spermatogenic cells. Data from the sperm number and motility as well as the fertility studies and the resulted litter size further points towards the antifertility effects of monensin in male rats. Genotoxicity tests were negative.

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Interactions
An experiment was carried out with male broiler chicks to evaluate the combined effect of monensin (150 mg/kg) & the growth promoters (GPs) Zn bacitracin (BAC, 50 mg/kg), virginiamycin (VIR, 25 mg/kg) & avoparcin (AVO, 20 mg/kg) fed from 7 to 28 days of age on performance, utilization of dietary nutrients, yield of defeathered eviscerated carcases (DEC) & size of various organs. The effect of the GPs in the monensin-unsupplemented diets fed up to 49 d of age on performance & carcase was also determined. Monensin significantly (P < 0.05) depressed food intake, weight gain & food efficiency from 7 to 28 d of age. None of the GPs was able to counteract these effects. However, AVO slightly ameliorated them. AVO also significantly increased food intake & improved gain & food efficiency during 7 to 28, but not 28 to 49 or 7 to 49 d of age. VIR & BAC did not affect performance in either age period. Monensin did not affect the utilisation of dietary dry matter, fat or energy, but it significantly decreased nitrogen utilisation. AVO improved nitrogen & fat utilisation & increased dietary AME(n) content. AME(n) was also increased by VIR. The utilisation of these nutrients was not affected by the interactions between monensin & the GPs. Monensin did not affect yield of the DEC or the relative liver size at 31 d of age. It significantly increased the relative length of the small intestine (SI) & decreased its specific weight. AVO significantly increased yield at 31, but not at 53 d of age. BAC & VIR did not affect this variable. AVO & VIR, but not BAC, at both age periods reduced, at times significantly, the size, length & specific weight of the SI. Our conclusions: BAC, VIR & AVO do not counteract the toxic effect of monensin. The effect of GPs in improving performance decreases & even disappears with age, while their effect in reducing the size of the SI is still evident in 49 day old birds.
In this study, co-admin of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin.
The characteristics of the toxic interaction between monensin & tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg & tiamulin 40 mg/kg bw, respectively). Monensin proved to be toxic to rats at doses of 30 & 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect & vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium & vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.
Cultured rat hepatocytes were treated with potassium cyanide, an inhibitor of cytochrome oxidase; valinomycin, a K+ ionophore; carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore; and the ATP synthetase inhibitor oligomycin. The effect of these agents on the viability of the cells was related to changes in ATP content and the deenergization of the mitochondria. The ATP content was reduced by over 90% by each inhibitor. All of the agents except oligomycin killed the cells within 4 h. With the exception of oligomycin, the mitochondrial membrane potential as measured by the distribution of [3H]triphenylmethylphosphonium collapsed with each of the agents. Monensin, a H+/Na+ ionophore, potentiated the toxicity of cyanide and CCCP, whereas the toxicity of valinomycin was reduced. The effect of cyanide and monesin on the cytoplasmic pH of cultured hepatocytes was measured with the fluorescent probe, 2',7'-biscarboxyethyl-5,6-carboxyfluorescein. Cyanide promptly acidified the cytosol, and the addition of 10 microM monensin caused a rapid alkalinization of the cytosol. A reduction of pH of the culture medium from 7.4 to 6.6 and 6.0 prevented the cell killing both by cyanide alone and by cyanide in the presence of monensin. However, neither monensin nor extracellular acidosis had any effect on the loss of mitochondrial energization in the presence of cyanide. It is concluded that ATP depletion per se is insufficient to explain the cell killing with cyanide, CCCP, and valinomycin. Rather, cell killing is better correlated with a loss of mitochondrial energization. With cyanide an intracellular acidosis interferes with the mechanism that couples collapse of the mitochondrial membrane potential to lethal cell injury.
For more Interactions (Complete) data for MONENSIN (9 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 100 mg/kg
LD50 Rat ip 15 mg/kg
LD50 Mouse oral 43,800 ug/kg
LD50 Mouse ip 10 mg/kg
LD50 Horse oral 2 mg/kg

[1]. Monensin inhibits epidermal growth factor receptor trafficking and activation: synergistic cytotoxicity in combination with EGFR inhibitors. Mol Cancer Ther. 2014 Nov;13(11):2559-71.

[2]. Monensin inhibits canonical Wnt signaling in human colorectal cancer cells and suppresses tumor growth in multiple intestinal neoplasia mice. Mol Cancer Ther. 2014 Apr;13(4):812-22.

[3]. Autophagy Participates in Lysosomal Vacuolation-Mediated Cell Death in RGNNV-Infected Cells. Front Microbiol. 2020 Apr 30:11:790.

[4]. Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic. 2005 Feb;6(2):131-43.

Therapeutic Uses
Antifungal Agents; Antiprotozoal Agents; Coccidiostats
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Monensin is included in the database.
MEDICATION (VET): Chickens: As an aid in the prevention of coccidiosis caused by Eimeria necatrix, E. tenella, E. acervulina, E. brunetti, E. mivati, and E. maxima. /Included in US product label/
MEDICATION (VET): Turkeys: For the prevention of coccidiosis in turkeys caused by Eimeria adenoeides, E. meleagrimitis and E. gallopavonis. /Included in US product label/
For more Therapeutic Uses (Complete) data for MONENSIN (12 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ Warning: Do not feed to laying chickens. Do not feed to chickens over 16 weeks of age. When mixing and handling Coban 90, use protective clothing, impervious gloves, and a dust mask. Operators should wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse thoroughly with water.
/BOXED WARNING/ Caution: For replacement chickens intended for use as cage layers only. Do not allow horses, other equines, mature turkeys, or guinea fowl access to feed containing monensin. Ingestion of monensin by horses and guinea fowl has been fatal. Some strains of turkey coccidia may be monensin tolerant or resistant. Monensin may interfere with development of immunity to turkey coccidiosis. In the absence of coccidiosis in broiler chickens the use of monensin with no withdrawal period may limit feed intake resulting in reduced weight gain.

C36H62O11

670.88

670.429

17090-79-8

Monensin sodium salt;22373-78-0

441145

Crystals

1.2±0.1 g/cm3

766.3±60.0 °C at 760 mmHg

103-105°C

229.2±26.4 °C

0.0±5.9 mmHg at 25°C

1.546

3.72

4

11

10

47

1110

17

O1[C@@]([H])(C([H])([H])C([H])([H])[C@@]1(C([H])([H])C([H])([H])[H])[C@@]1([H])[C@@]([H])(C([H])([H])[H])C([H])([H])[C@]([H])([C@]2([H])[C@@]([H])(C([H])([H])[H])C([H])([H])[C@@]([H])(C([H])([H])[H])[C@@](C([H])([H])O[H])(O[H])O2)O1)[C@]1(C([H])([H])[H])C([H])([H])C([H])([H])[C@]2(C([H])([H])[C@@]([H])([C@@]([H])(C([H])([H])[H])[C@@]([H])([C@@]([H])(C([H])([H])[H])[C@]([H])([C@@]([H])(C(=O)O[H])C([H])([H])[H])OC([H])([H])[H])O2)O[H])O1

GAOZTHIDHYLHMS-KEOBGNEYSA-N

InChI=1S/C36H62O11/c1-10-34(31-20(3)16-26(43-31)28-19(2)15-21(4)36(41,18-37)46-28)12-11-27(44-34)33(8)13-14-35(47-33)17-25(38)22(5)30(45-35)23(6)29(42-9)24(7)32(39)40/h19-31,37-38,41H,10-18H2,1-9H3,(H,39,40)/t19-,20-,21+,22+,23-,24-,25-,26+,27+,28-,29+,30-,31+,33-,34-,35+,36-/m0/s1

(2S,3R,4S)-4-[(2S,5R,7S,8R,9S)-2-[(2R,5S)-5-ethyl-5-[(2R,3S,5R)-5-[(2S,3S,5R,6R)-6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]oxolan-2-yl]-7-hydroxy-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-3-methoxy-2-methylpentanoic acid

Rumensin; Elancoban; monensin; monensin A; Monensic acid; Monensinum; Monensina; 17090-79-8; Elancoban; Monelan; Monensin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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