| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
Antibiotic/antibacterial
Gentamicin C1a primarily targets the 30S ribosomal protein S12 and 16S ribosomal RNA in bacteria. These targets play a crucial role in bacterial protein synthesis. The compound binds to the aminoacyl site on 16S rRNA of the 30S subunit in the bacterial ribosome. |
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| ln Vitro |
Gentamicin C1a has an IC50 value of 1 mg/mL and inhibits the growth of Escherichia coli, P. aeruginosa, and S. aureus[2]. OC-k3 cell viability is unaffected by gentamicin C1a (2 mM, 48 h) [2].
In vitro, Gentamicin C1a inhibits the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The compound exhibits an IC50 value of 1 mg/mL against these pathogens. Gentamicin C1a shows lower MIC values than gentamicin C1 against S. aureus and P. aeruginosa strains. It has an EC50 of 821 +/- 24 microM. OC-k3 cell viability is unaffected by gentamicin C1a at 2 mM for 48 hours. |
| ln Vivo |
Gentamicin C1a (4 mg/kg, intravenous bolus dosage, single dose) had an average residence time of 84 minutes in beagle dogs and a CL value of 1.81 mL/min/kg[3].
In vivo, Gentamicin C1a (4 mg/kg, intravenous bolus dose, single) shows a mean residence time of 84 minutes and a clearance (CL) value of 1.81 mL/min/kg in beagles. In infected piglets, exposure to the compound was found to be lower and it was eliminated faster compared to healthy piglets. The compound exhibits antibacterial activity in animal models of infection. |
| Enzyme Assay |
Gentamicin C1a is the precursor of the semi-synthetic antibiotic etimicin and has the highest antibacterial activity in the clinically important gentamicin C mixture. To obtain a gentamicin C1a-overproducing strain, we inactivated gacD gene in Micromonospora purpurea. The gacD was presumed to encode a C6' methyltransferase by sequence analysis, and plays a role in the conversion of the gentamicin intermediate X2 to G418. So the inactivation of gacD blocks the metabolic pathways from X2 to G418 and leads to the accumulation of gentamicin C1a.The resulting recombination strain produced gentamicin C1a more than 10-fold compared to the wild type strain. Moreover, the wild-type strain produced 4 main production components, C1a, C2, C2a and C1, while the recombination strain produced only 2 components, C1a and C2b, making the purification of gentamicin C1a easier. The recombination strain was genetically stable and should be useful for the industrial production of gentamicin C1a[1].
In vitro enzyme/receptor binding assays for Gentamicin C1a involve evaluating its binding to the bacterial 30S ribosomal subunit. Binding studies typically use radiolabeled gentamicin or fluorescence-based assays with purified ribosomes or 16S rRNA. The compound binds in the major groove of the RNA, directing specific RNA-drug interactions. Binding affinity and specificity are determined by measuring displacement of labeled probes or changes in fluorescence polarization. |
| Cell Assay |
Spread of antimicrobial resistance and shortage of novel antibiotics have led to an urgent need for new antibacterials. Although aminoglycoside antibiotics (AGs) are very potent anti-infectives, their use is largely restricted due to serious side-effects, mainly nephrotoxicity and ototoxicity. We evaluated the ototoxicity of various AGs selected from a larger set of AGs on the basis of their strong antibacterial activities against multidrug-resistant clinical isolates of the ESKAPE panel: gentamicin, gentamicin C1a, apramycin, paromomycin and neomycin. Following local round window application, dose-dependent effects of AGs on outer hair cell survival and compound action potentials showed gentamicin C1a and apramycin as the least toxic. Strikingly, although no changes were observed in compound action potential thresholds and outer hair cell survival following treatment with low concentrations of neomycin, gentamicin and paromomycin, the number of inner hair cell synaptic ribbons and the compound action potential amplitudes were reduced. This indication of hidden hearing loss was not observed with gentamicin C1a or apramycin at such concentrations. These findings identify the inner hair cells as the most vulnerable element to AG treatment, indicating that gentamicin C1a and apramycin are promising bases for the development of clinically useful antibiotics[2].
In vitro cell-based assays for Gentamicin C1a involve standard antimicrobial susceptibility testing using broth microdilution methods to determine minimum inhibitory concentrations (MIC) against various bacterial strains. Cells are cultured in appropriate media, treated with serial dilutions of the compound, and incubated at 37degC for 18-24 hours. MIC values are read as the lowest concentration that inhibits visible bacterial growth. Cytotoxicity is assessed using mammalian cell lines such as OC-k3 cells. |
| Animal Protocol |
The pharmacokinetics of gentamicin C(1), C(2), and C(1a) were studied in six beagles after administration of gentamicin at 4 mg/kg of body weight as a single intravenous bolus dose. Plasma concentrations of the gentamicin components were analyzed with a novel high-performance liquid chromatography method capable of identifying and quantifying each of the components. The pharmacokinetic analysis of the plasma concentration-versus-time data was performed using the noncompartmental approach. The results indicated significant differences in the pharmacokinetic characteristics between the gentamicin components C(1), C(1a), and C(2). The mean residence times of gentamicin C(1), C(1a), and C(2) were 81+/-13, 84+/-12, and 79+/-13 min (mean +/- standard deviation), respectively. The half-lives of the respective components were 64+/-12, 66+/-12 and 63+/-12 min. Clearance (CL) of gentamicin C(1), 4.62+/-0.71 ml min(-1) kg(-1), was significantly higher (P = 0.0156) than CL of gentamicin C(1a), 1.81+/-0.26 ml min(-1) kg(-1), and C(2), 1.82+/-0.25 ml min(-1) kg(-1). Similarly, the volume of distribution at steady state (V(ss)) of gentamicin C(1), 0.36+/-0.04 liter kg(-1), was significantly higher (P = 0.0156) than the V(ss) of gentamicin C(1a), 0.14+/-0.01 liter kg(-1), and C(2), 0.15+/-0.02 liter kg(-1). Tissue binding was considered the most likely cause for the difference. The difference may have clinical and toxicological significance.[3]
In vivo animal studies for Gentamicin C1a typically use rodent or canine models of bacterial infection. The compound is administered via intravenous, intramuscular, or subcutaneous routes at various doses. Infected animals are treated and monitored for bacterial clearance, survival, and clinical signs. Pharmacokinetic parameters such as residence time and clearance are determined from plasma concentration-time profiles. Tissue distribution and efficacy are evaluated post-mortem. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Gentamicin C1a include a mean residence time of 84 minutes and a clearance of 1.81 mL/min/kg in beagles following intravenous bolus dosing. In neonates, clearance is influenced by changes in the glomerular filtration rate. The compound's pharmacokinetics involve absorption, distribution, metabolism, and excretion (ADME) factors. In infected piglets, exposure is lower and elimination is faster compared to healthy animals.
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| Toxicity/Toxicokinetics |
Toxicity of Gentamicin C1a is characteristic of aminoglycoside antibiotics. Potential toxicities include nephrotoxicity (kidney damage) and ototoxicity (hearing loss) associated with prolonged or high-dose exposure. The compound is for research use only and not for human therapeutic use. In vitro cytotoxicity studies show OC-k3 cell viability is unaffected at 2 mM for 48 hours. Comprehensive toxicity profiling would require standard preclinical safety studies.
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| References |
[1]. Li D, et al. Construction of a gentamicin C1a-overproducing strain of Micromonospora purpurea by inactivation of the gacD gene. Microbiol Res. 2013 Jun 12;168(5):263-7.
[2]. Ishikawa M, et al. Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use. Sci Rep. 2019 Feb 20;9(1):2410. [3]. Isoherranen N, et al. Pharmacokinetics of gentamicin C(1), C(1a), and C(2) in beagles after a single intravenous dose. Antimicrob Agents Chemother. 2000 Jun;44(6):1443-7. |
| Additional Infomation |
Gentamicin C1a is a derivative of gentamicin C and is the conjugated base of gentamicin C1a(5+). Gentamicin C1a has been reported to exist in Cordyceps militaris, Serratia plymouthii, and other organisms with relevant data. Gentamicin C1a is one of the major components of gentamicin complexes. Gentamicin C1a lacks a methyl group on its 2-aminohexose ring and has a free amino group at the 6' position.
Gentamicin C1a is the precursor of the semi-synthetic antibiotic Etimicin. It is one of the major components of the gentamicin complex produced by Micromonospora species. The compound is active primarily against aerobic Gram-negative bacilli including Pseudomonas aeruginosa, Escherichia coli, Klebsiella and Enterobacter species. It is frequently used in combination with cell wall active agents for severe Gram-positive infections where synergy is desired. |
| Molecular Formula |
C19H39N5O7
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|---|---|
| Molecular Weight |
449.54
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| Exact Mass |
449.285
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| CAS # |
26098-04-4
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| PubChem CID |
72396
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| Appearance |
Typically exists as
White to off-white solid at room temperature
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| Density |
1.36g/cm3
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| Boiling Point |
675.2ºC at 760 mmHg
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| Melting Point |
102-108ºC
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| Flash Point |
362.1ºC
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| Vapour Pressure |
3.97E-21mmHg at 25°C
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| Index of Refraction |
1.603
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| LogP |
-5
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
592
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| Defined Atom Stereocenter Count |
12
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| SMILES |
[NH3+]CC1CCC([NH3+])C(OC2C([NH3+])CC([NH3+])C(OC3OCC(C)(O)C([NH2+]C)C3O)C2O)O1
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| InChi Key |
VEGXETMJINRLTH-BOZYPMBZSA-N
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| InChi Code |
InChI=1S/C19H39N5O7/c1-19(27)7-28-18(13(26)16(19)24-2)31-15-11(23)5-10(22)14(12(15)25)30-17-9(21)4-3-8(6-20)29-17/h8-18,24-27H,3-7,20-23H2,1-2H3/t8-,9+,10-,11+,12-,13+,14+,15-,16+,17+,18+,19-/m0/s1
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| Chemical Name |
(2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol
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| Synonyms |
Gentamycin C1A; Gentamycin C12; Gentamicin Cla; AV4A72IATD; CHEBI:27784; (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : 250 mg/mL (556.12 mM)
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2245 mL | 11.1225 mL | 22.2450 mL | |
| 5 mM | 0.4449 mL | 2.2245 mL | 4.4490 mL | |
| 10 mM | 0.2224 mL | 1.1122 mL | 2.2245 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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