| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Oligosaccharide antibiotic
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|---|---|
| ln Vitro |
Paromomycin is a broad spectrum aminoglycoside antibiotic produced by Streptomyces rimosus var. paromomycinus. The in vitro and in vivo antibacterial action of paromomycin closely parallels that of neomycin.
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| ln Vivo |
Paromomycin is used for the treatment of acute and chronic intestinal amebiasis (it is not effective in extraintestinal amebiasis). Also for the management of hepatic coma as adjunctive therapy.
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| Enzyme Assay |
Despite the WHO's recommended treatment regimen, challenges such as patient non-adherence and the emergence of drug-resistant strains persist with TB claiming 1.5 million lives annually. In this study, we propose a novel approach by targeting the DNA replication-machinery of M.tb through drug-repurposing. The β2-Sliding clamp (DnaN), a key component of this complex, emerges as a potentially vulnerable target due to its distinct structure and lack of human homology. Leveraging TBVS, we screened ∼2600 FDA-approved drugs, identifying five potential DnaN inhibitors, by employing computational studies, including molecular-docking and molecular-dynamics simulations. The shortlisted compounds were subjected to in-vitro and ex-vivo studies, evaluating their anti-mycobacterial potential. Notably, Dicoumarol, Paromomycin, and Posaconazole exhibited anti-TB properties with a MIC value of 6.25, 3.12 and 50 μg/ml respectively, with Dicoumarol and Paromomycin, demonstrating efficacy in reducing live M.tb within macrophages. Biophysical analyses confirmed the strong binding-affinity of DnaNdrug complexes, validating our in-silico predictions. Moreover, RNA-Seq data revealed the upregulation of proteins associated with DNA repair and replication mechanisms upon Paromomycin treatment. This study explores repurposing FDA-approved drugs to target TB via the mycobacterial DNA replication-machinery, showing promising inhibitory effects. It sets the stage for further clinical research, demonstrating the potential of drug repurposing in TB treatment. [1]
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| ADME/Pharmacokinetics |
Absorption
Poor absorption after oral administration; almost 100% of the drug is recovered in the feces. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no information regarding the clinical use of paromomycin during lactation. Due to poor oral absorption of paromomycin, it is unlikely to enter the infant's bloodstream and is unlikely to cause any adverse effects on breastfed infants. ◉ Effects on Breastfed Infants As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk As of the revision date, no relevant published information was found. 165580 Rat Oral LD50 21620 mg/kg Lung, pleural cavity or respiration: respiratory depression; skin and appendages (skin): hair: Other chemotherapy, 16(124), 1968 165580 Rat LD50 Subcutaneous injection 1010 mg/kg Antibiotics and Chemotherapy, 12(243), 1962 165580 Rat LD50 Intravenous injection 156 mg/kg Presse Medicale., 70(127), 1962 [PMID:13872889] 165580 Rat LD50 Intramuscular injection 1200 mg/kg Behavior: rigidity; lung, pleural cavity or respiration: dyspnea; skin and appendages (skin): hair: Other chemotherapy, 16(124), 1968 165580 Mouse Oral LD50 2275 mg/kg Antibiotics: Origin, Properties and Characteristics, Korzyoski, T. et al., eds., American Society for Microbiology, Washington, D.C., 1978, 1(674), 1978 |
| References |
[1]. Revitalizing antimicrobial strategies: paromomycin and dicoumarol repurposed as potent inhibitors of M.tb's replication machinery via targeting the vital protein DnaN. Int J Biol Macromol. 2024 Oct;278(Pt 3):134652.
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| Additional Infomation |
Paromomycin sulfate is an aminoglycoside sulfate produced by reacting paromomycin with sulfuric acid. It is a broad-spectrum antibiotic used to treat acute and chronic intestinal protozoan infections, but ineffective against extraintestinal protozoan infections. It is also used to treat visceral leishmaniasis. It has dual antibacterial, antiprotozoal, anthelmintic, and antiparasitic effects. Its function is related to paromomycin. Paromomycin sulfate is the sulfate form of paromomycin, a structural derivative of neomycin, an aminoglycoside antibiotic with amoebic and bactericidal activity against predominantly aerobic Gram-negative bacteria. Paromomycin specifically binds to the RNA oligonucleotide at the 30S ribosomal A site of bacteria, leading to mRNA translation misreading and premature termination, inhibiting protein synthesis, and ultimately causing cell death. It is an aminoglycoside antibacterial and antiprotozoal drug produced by Streptomyces.
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| Molecular Formula |
C23H45N5O14
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|---|---|
| Molecular Weight |
615.63
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| Exact Mass |
615.296
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| Elemental Analysis |
C, 44.87; H, 7.37; N, 11.38; O, 36.38
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| CAS # |
7542-37-2
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| Related CAS # |
7205-49-4; 1263-89-4; 7542-37-2 (Parent); 7542-37-2 (Parent)
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| PubChem CID |
441375
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.64g/cm3
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| Boiling Point |
939.8ºC at 760 mmHg
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| Flash Point |
522.2ºC
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| Index of Refraction |
1.676
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| Source |
Streptomyces and Streptomyces rimosus
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| Hydrogen Bond Donor Count |
15
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| Hydrogen Bond Acceptor Count |
23
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
47
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| Complexity |
952
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| Defined Atom Stereocenter Count |
19
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| SMILES |
C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)N)O[C@H]3[C@@H]([C@@H]([C@@H](CO)O3)O[C@@H]4[C@@H]([C@H]([C@@H]([C@H](CN)O4)O)O)N)O)O)N
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| InChi Key |
LJRDOKAZOAKLDU-UDXJMMFXSA-N
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| InChi Code |
InChI=1S/C23H45N5O14.H2O4S/c24-2-7-13(32)15(34)10(27)21(37-7)41-19-9(4-30)39-23(17(19)36)42-20-12(31)5(25)1-6(26)18(20)40-22-11(28)16(35)14(33)8(3-29)38-22;1-5(2,3)4/h5-23,29-36H,1-4,24-28H2;(H2,1,2,3,4)/t5-,6+,7+,8-,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+;/m1./s1
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| Chemical Name |
(2S,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(2R,3S,4R,5S)-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric acid
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| Synonyms |
R-400; paromomycin; catenulin; Aminosidin; Neomycin E; Hydroxymycin; AMINOSIDINE; Monomycin A; ...; 7542-37-2; R 400; Paromomycin
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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 |
| 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) |
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
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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 | 1.6244 mL | 8.1218 mL | 16.2435 mL | |
| 5 mM | 0.3249 mL | 1.6244 mL | 3.2487 mL | |
| 10 mM | 0.1624 mL | 0.8122 mL | 1.6244 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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