Quinupristin/dalfopristin is an antibiotic combination including streptomycins that is used to treat infections. There have been reports of quinupristin/dalfopristin's effectiveness against Mycoplasma species.[1].

Absorption, Distribution and Excretion
Quinuprine and dalfopristin are distributed in the milk of rats… The pharmacokinetics of quinuprine/dalfopristin following intravenous infusion of radiolabeled and unlabeled drugs have been studied in rats, monkeys, and humans. In rats and monkeys, quinuprine and dalfopristin are rapidly eliminated from the blood and widely distributed in tissues. However, they enter the central nervous system or cross the placenta with minimal penetration and appear not to remain significantly in the body after discontinuation of administration. The blood elimination half-life of quinuprine is approximately 0.6 hours in rats and approximately 0.5 hours in monkeys; the blood elimination half-life of dalfopristin is approximately 0.6 hours in rats and approximately 0.2 hours in monkeys. Both compounds are primarily excreted into feces via bile; quinuprine is primarily excreted unchanged, while dalfopristin requires extensive prior metabolism. The metabolites of dalfopristin include the microbially active prostatin PIIA, while the metabolites of quinupristin include microbially active glutathione and cysteine-conjugated derivatives. Quinupristin and dalfopristin appear to be metabolized similarly in humans. Following intravenous administration, both compounds are rapidly cleared from the bloodstream, with an elimination half-life of approximately 1 hour for quinupristin and approximately 0.4–0.5 hours for dalfopristin. The pharmacokinetic characteristics of quinupristin are dose-independent, as is the case when dalfopristin is used in combination with RP 12536. Extravascular diffusion of quinupristin/dalfopristin has been evaluated in human non-inflammatory interstitial fluid. Fecal excretion is the primary route of elimination for both parent drugs and their metabolites (75% to 77% of the dose). Urinary excretion accounts for approximately 15% of the quinupristin dose and 19% of the dalfopristin dose. Preclinical rat data showed that approximately 80% of the dose was excreted via bile, suggesting that bile excretion is likely the primary fecal excretion route in humans. Metabolism/Metabolites Quinuprine is converted into two bound active metabolites, one bound to glutathione and the other to cysteine. Quinuprine and dalfopristin are converted into several major active metabolites: two bound metabolites of quinuprine (bound to glutathione and cysteine, respectively) and one unbound metabolite of dalfopristin (formed by hydrolysis). These metabolites also exhibit synergistic effects with their complementary parent drugs. This conversion occurs in vitro via a non-enzymatic reaction, independent of cytochrome P-450 (CYP) and glutathione transferase. Biological Half-Life 3.1 hours The elimination half-lives of quinuprine and dalfopristin are approximately 0.85 hours and 0.70 hours, respectively. The pharmacokinetics of quinuprine/dalfopristin following intravenous infusion of radiolabeled and unlabeled drugs have been studied in rats, monkeys, and humans. …The blood elimination half-life of quinuprine in rats is approximately 0.6 hours and in monkeys approximately 0.5 hours; the blood elimination half-life of dalfopristin in rats is approximately 0.6 hours and in monkeys approximately 0.2 hours. Following intravenous injection, both compounds are rapidly cleared from the bloodstream, with an elimination half-life of approximately 1 hour for quinuprine and approximately 0.4–0.5 hours for dalfopristin.

Protein binding is moderate.

[1]. Gurk-Turner C. Quinupristin/dalfopristin: the first available macrolide-lincosamide-streptogramin antibiotic. Proc (Bayl Univ Med Cent). 2000 Jan;13(1):83-6.
[2]. Tantibhedhyangkul W, et al. Anti-Mycoplasma Activity of Daptomycin and Its Use for Mycoplasma Elimination in Cell Cultures of Rickettsiae. Antibiotics (Basel). 2019 Aug 21;8(3).

Quinuprine/dalfopristin is a combination of two antibiotics used to treat staphylococcal infections and vancomycin-resistant Enterococcus faecalis infections. Dalfopristin inhibits the early stages of bacterial ribosomal protein synthesis, while quinuprine inhibits the later stages. The combination of the two components has a synergistic effect, resulting in superior in vitro efficacy compared to either component alone. Quinuprine is a streptomycin antibiotic. Quinuprine is a semi-synthetic derivative of prolistatin, a naturally occurring type B streptomycin. Quinuprine binds to the bacterial 50S ribosomal subunit, thereby inhibiting peptide chain elongation and causing premature termination of normal bacterial protein synthesis. Quinuprine is primarily effective against Gram-positive cocci. Drug Indications: For the treatment of bacterial infections (usually used in combination with dalfopristin). FDA Label: Mechanism of Action: Quinuprine inhibits the later stages of bacterial ribosomal protein synthesis. Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, altering its conformation and increasing quinuprentice binding affinity by approximately 100-fold. Furthermore, it inhibits peptidyl transferases. Quinuprentice binds to adjacent sites on the 50S ribosomal subunit, preventing polypeptide chain elongation and leading to the release of incomplete polypeptide chains. The sites of action for both quinuprentice and dalfopristin are bacterial ribosomes. Dalfopristin has been shown to inhibit the early stages of protein synthesis, while quinuprentice inhibits the later stages. Synercid exhibits bactericidal activity against both methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates. Synercid's mechanism of action differs from that of other antimicrobial agents such as β-lactams, aminoglycosides, glycopeptides, quinolones, macrolides, lincosamides, and tetracyclines. Therefore, using the minimum inhibitory concentration (MIC) method, no cross-resistance was found between Synercid and these drugs. Quinuprine and daffodil have unique pharmacological mechanisms, respectively, by binding to different sites on the 50S subunit of the bacterial ribosome, inhibiting protein synthesis in the later stages (peptide chain elongation inhibition) and the early stages (peptidyl transferase inhibition and the resulting conformational changes). No antagonistic effects against β-lactams, aminoglycosides, glycopeptides, quinolones, macrolides, lincosamides, or tetracyclines were observed in in vitro experiments. Bacterial ribosomes are a major target for many antibiotics. Studying the structure of ribosomal subunit complexes with different antibiotics can reveal the inhibitory patterns of ribosomal protein synthesis. Analyzing the interaction between antibiotics and ribosomes helps to investigate the specific roles of modifications leading to antimicrobial resistance. Streptomycin antibiotics are unique among ribosome-targeting antibiotics because they consist of two components, streptomycin A and streptomycin B, which have a synergistic effect. Each component exhibits weak antibacterial activity when used alone, but the combination has bactericidal activity. Streptomycin A has durable activity, persisting even after discontinuation. However, despite a wealth of biochemical and structural data, the mechanism of action of streptomycin remains incompletely elucidated. Results: Crystal structure studies of the 50S ribosomal subunit of Streptomyces radiodurans and the clinically relevant streptomycin antibiotics quinuprine and daffoprine revealed their unique inhibitory mechanisms. Quinuprine, a streptomycin class B compound, binds to the ribosomal exit channel in a similar manner and position to macrolide antibiotics, suggesting a similar inhibitory mechanism: blocking ribosomal channels. The corresponding streptomycin class A compound, daffoprine, binds directly to the peptidyl transferase center, closely adjacent to quinuprine, influencing the occupancy of the A and P sites on the tRNA molecule. Crystal structures indicate that this synergistic effect stems from the direct interaction between the two compounds and their co-contact with the single nucleotide A2062. Upon binding to the streptomycin antibiotics, a significant conformational change occurs at the peptidyl transferase center, resulting in a stable nonfunctional orientation of the universally conserved U2585 base. Mutations in this rRNA base are known to lead to a dominant lethal phenotype. Therefore, it is reasonable to conclude that the conformational change of the peptidyl transferase center is the main reason for the bactericidal activity of streptomycin antibiotics and the inhibition of protein synthesis after antibiotic treatment.

C53H67N9O10S

1022.22

1021.47

120138-50-3

Quinupristin mesylate

5388937

White to slightly yellow powder
White crystals in combination with methanol

1.38g/cm3

approximately 200 °C

1.662

3.123

4

14

10

73

2010

9

CC[C@@H]1C(=O)N2CCC[C@H]2C(=O)N([C@H](C(=O)N3C[C@H](C(=O)C[C@H]3C(=O)N[C@H](C(=O)O[C@@H]([C@@H](C(=O)N1)NC(=O)C4=C(C=CC=N4)O)C)C5=CC=CC=C5)CS[C@@H]6CN7CCC6CC7)CC8=CC=C(C=C8)N(C)C)C

WTHRRGMBUAHGNI-LCYNINFDSA-N

InChI=1S/C53H67N9O10S/c1-6-37-50(68)61-23-11-14-38(61)51(69)59(5)40(26-32-16-18-36(19-17-32)58(3)4)52(70)62-28-35(30-73-43-29-60-24-20-33(43)21-25-60)42(64)27-39(62)47(65)57-45(34-12-8-7-9-13-34)53(71)72-31(2)44(48(66)55-37)56-49(67)46-41(63)15-10-22-54-46/h7-10,12-13,15-19,22,31,33,35,37-40,43-45,63H,6,11,14,20-21,23-30H2,1-5H3,(H,55,66)(H,56,67)(H,57,65)/t31-,35+,37-,38+,39+,40+,43-,44+,45+/m1/s1

N-[(3S,6S,12R,15S,16R,19S,22S,25R)-25-[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]sulfanylmethyl]-3-[[4-(dimethylamino)phenyl]methyl]-12-ethyl-4,16-dimethyl-2,5,11,14,18,21,24-heptaoxo-19-phenyl-17-oxa-1,4,10,13,20-pentazatricyclo[20.4.0.06,10]hexacosan-15-yl]-3-hydroxypyridine-2-carboxamide

Antibiotic RP 57669 QuinupristinQuinupristin RP 68888 RP 57669 RP57669RP-68888 RP68888 RP-57669

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)

DMSO : ~125 mg/mL (~122.28 mM)

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.)