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Clinafloxacin hydrochloride (PD127391)

Alias: CI-960; PD-127391; AM-109; CI960; PD127391; AM109; Clinafloxacin hydrochloride; Clinafloxacin HCl; CI-960 HCl; UNII-G17M59V0FY ;CI 960 HCl
Cat No.:V18484 Purity: ≥98%
Clinafloxacin HCl (also known as CI-960, PD127391, AM-1091), thehydrochloridesalt of Clinafloxacin, is an investigational, broad-spectrumfluoroquinolone class of antibiotic that inhibits both DNA gyrase and topoisomerase IV dually in Streptococcus pneumonia.
Clinafloxacin hydrochloride (PD127391)
Clinafloxacin hydrochloride (PD127391) Chemical Structure CAS No.: 105956-99-8
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
25mg
50mg
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Other Forms of Clinafloxacin hydrochloride (PD127391):

  • Clinafloxacin (AM-1091; CI-960)
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Clinafloxacin HCl (also known as CI-960, PD127391, AM-1091), the hydrochloride salt of Clinafloxacin, is an investigational, broad-spectrum fluoroquinolone class of antibiotic that inhibits both DNA gyrase and topoisomerase IV dually in Streptococcus pneumonia. The quinolone carboxylic acid class of broad-spectrum antibiotics is presently being developed for oral and intravenous treatment of serious infections. With strong broad-spectrum in vitro activity against gram-positive, gram-negative, and anaerobic pathogens, clinafloxacin is a novel fluoroquinolone antibiotic.

Biological Activity I Assay Protocols (From Reference)
Targets
Topoisomerase IV; DNA gyrase
ln Vitro
Clinafloxacin shows efficacy against S. pneumonia in parC-gyrA mutants, with a minimum inhibitory concentration (MIC) of 1 μg/ml[2].
Clinafloxacin hydrochloride possesses antibacterial properties against S. aureus mutant strains with altered targets. It has MIC values of 0.016 µg/ml, 0.063 µg/ml, and 0.915 µg/ml against wild type S. aureus, gyrA mutant S. aureus, and gyrA mutant S. aureus, respectively[3].
ln Vivo
Clinafloxacin pneumococcal meningitis that is resistant to penicillin responds well to clinafloxacin therapy in the rabbit model.
Clinafloxacin produces an initial reduction at 6 hours when used with the CS strain (2349) (Clinafloxacin MIC=0.12 μg/ml) at doses of 10 mg/kg and 20 mg/kg. The final reduction in mean log cfu/ml at 24 hours is 22.30 and 23.83, respectively. Both are bactericidal at this point, but show regrowth at that time. But in this meningitis model in rabbits, even at 20 mg/kg per day, clinafloxacin (MIC=0.5 μg/ml) does not reduce bacterial titers[3]. This is because the CR strain (4371) exhibits this property.
Enzyme Assay
The antibacterial activities and target inhibition of 15 quinolones against grlA and gyrA mutant strains were studied. The strains were obtained from wild-type Staphylococcus aureus MS5935 by selection with norfloxacin and nadifloxacin, respectively. The antibacterial activities of most quinolones against both mutant strains were lower than those against the wild-type strain. The ratios of MICs for the gyrA mutant strain to those for the grlA mutant strain (MIC ratio) varied from 0.125 to 4. The ratios of 50% inhibitory concentrations (IC50s) of quinolones against topoisomerase IV to those against DNA gyrase (IC50 ratios) also varied, from 0.177 to 5.52. A significant correlation between the MIC ratios and the IC50 ratios was observed (r = 0.919; P < 0.001). These results suggest that the antibacterial activities of quinolones against the wild-type strain are involved not only in topoisomerase IV inhibition but also in DNA gyrase inhibition and that the target preference in the wild-type strain can be anticipated by the MIC ratios. Based on the MIC ratios, the quinolones were classified into three categories. Type I quinolones (norfloxacin, enoxacin, fleroxacin, ciprofloxacin, lomefloxacin, trovafloxacin, grepafloxacin, ofloxacin, and levofloxacin) had MIC ratios of <1, type II quinolones (sparfloxacin and nadifloxacin) had MIC ratios of >1, and type III quinolones (gatifloxacin, pazufloxacin, moxifloxacin, and clinafloxacin) had MIC ratios of 1. Type I and type II quinolones seem to prefer topoisomerase IV and DNA gyrase, respectively. Type III quinolones seem to target both enzymes at nearly the same level in bacterial cells (a phenomenon known as the dual-targeting property), and their IC50 ratios were approximately 2[1].
Animal Protocol
The increasing incidence of ciprofloxacin resistance in Streptococcus pneumoniae may limit the efficacy of the new quinolones in difficult-to-treat infections such as meningitis. The aim of the present study was to determine the efficacy of clinafloxacin alone and in combination with teicoplanin and rifampin in the therapy of ciprofloxacin-susceptible and ciprofloxacin-resistant pneumococcal meningitis in rabbits. When used against a penicillin-resistant ciprofloxacin-susceptible strain (Clinafloxacin MIC 0.12 microg/ml), clinafloxacin at a dose of 20 mg/kg per day b.i.d. decreased bacterial concentration by -5.10 log cfu/ml at 24 hr. Combinations did not improve activity. The same clinafloxacin schedule against a penicillin- and ciprofloxacin-resistant strain (Clinafloxacin MIC 0.5 microg/ml) was totally ineffective. Our data suggest that a moderate decrease in quinolone susceptibility, as indicated by the detection of any degree of ciprofloxacin resistance, may render these antibiotics unsuitable for the management of pneumococcal meningitis[3].
References

[1]. Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition.Antimicrob Agents Chemother. 2001 Dec;45(12):3544-7.

[2]. DNA Gyrase and Topoisomerase IV Mutations and their effect on Quinolones Resistant Proteus mirabilis among UTIs Patients. Pak J Med Sci. Sep-Oct 2020;36(6):1234-1240.

[3]. Experimental study of clinafloxacin alone and in combination in the treatment of ciprofloxacin-susceptible and -resistant pneumococcal meningitis.Microb Drug Resist. 2003;9 Suppl 1:S53-9.

Additional Infomation
7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-4-oxo-3-quinolinecarboxylic acid is a member of quinolines. Clinafloxacin is a fluoroquinolone antibacterial currently under research. It has been proven to present good antibiotic properties. However, its approval and release have been halted due to the presence of serious side effects.
Objective: This study aimed to highlight the importance of mutations within Proteus mirabilis genome that are related to fluoroquinolone resistance. Methods: This is a cross sectional study performed in different teaching hospitals in Khartoum State from June 2016 to May 2017. A total of (120) P mirabilis isolates from patients with symptoms of UTIs attending different hospitals in Khartoum State were examined. First, modified Kurby Bauer method was performed for phenotypical detection of resistant isolates. Then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing were applied for detection of mutations in GyrA, GyrB, ParC and ParE genes of isolates. Results: P. mirabilis showed 30% resistance to ciprofloxacin. All samples revealed mutation at (serine 83) of GyrA and (serine 84) of ParC by Hinf1 restriction endonuclease digestion. Sequencing was performed for 12 samples. For each gene, two resistant and one susceptible strains were randomly selected. The mutations associated with ciprofloxacin resistant P. mirabilis were as follows; (1/3) GyrA (Ser 83 to Ile) and (2/3) ParC (Ser 81 to Ile). Also it revealed silent mutations at codons of GyrB 474 leucine (3/3), 585 valine (2/3), 612 histidine (1/3) and 639 asparagine (1/3) and ParE 469 isoleucine (2/3), 531 aspartic (2/3) and 533 glycine (1/3). Conclusions: Ciprofloxacin resistance in P. mirabilis could be monitored through detection of mutations within DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE).[2]
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H18CL2FN3O3
Molecular Weight
402.24752
Exact Mass
401.07
Elemental Analysis
C, 50.76; H, 4.51; Cl, 17.63; F, 4.72; N, 10.45; O, 11.93
CAS #
105956-99-8
Related CAS #
105956-97-6; 105956-99-8 (HCl)
PubChem CID
60062
Appearance
Solid powder
Density
1.573 g/cm3
Boiling Point
592.3ºCat 760 mmHg
Melting Point
162-168°C
Flash Point
312ºC
LogP
3.931
Hydrogen Bond Donor Count
3
Hydrogen Bond Acceptor Count
7
Rotatable Bond Count
3
Heavy Atom Count
26
Complexity
626
Defined Atom Stereocenter Count
0
SMILES
C1CC1N2C=C(C(=O)C3=C2C(=C(C(=C3)F)N4CCC(C4)N)Cl)C(=O)O.Cl
InChi Key
BMACYHMTJHBPOX-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H17ClFN3O3.ClH/c18-13-14-10(5-12(19)15(13)21-4-3-8(20)6-21)16(23)11(17(24)25)7-22(14)9-1-2-9;/h5,7-9H,1-4,6,20H2,(H,24,25);1H
Chemical Name
7-(3-aminopyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid;hydrochloride
Synonyms
CI-960; PD-127391; AM-109; CI960; PD127391; AM109; Clinafloxacin hydrochloride; Clinafloxacin HCl; CI-960 HCl; UNII-G17M59V0FY ;CI 960 HCl
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

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
5%TFA: ~3.02 mg/mL
DMSO: ~0.03 mg/mL (~0.08 mM)
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
(e.g. IP/IV/IM/SC)
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 : PEG300Tween 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 : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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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


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.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4860 mL 12.4301 mL 24.8602 mL
5 mM 0.4972 mL 2.4860 mL 4.9720 mL
10 mM 0.2486 mL 1.2430 mL 2.4860 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Antimicrob Agents Chemother . 2001 Dec;45(12):3544-7.
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