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Cadazolid, also known ACT-179811, is a novel fluoroquinolone-oxazolidinone antibiotic and a protein synthesis inhibitor. Cadazolid may be potentially useful for the treatment of Clostridium difficile infection. Cadazolid exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. Clostridium difficile infection (CDI), the main cause of nosocomial infectious diarrhea, results from the growth of toxin-producing C. difficile in the colon following disruption of the normal enteric microbiota, usually as a consequence of antibiotic therapy.
Physicochemical Properties
| Molecular Formula | C29H29F2N3O8 |
| Molecular Weight | 585.56 |
| Exact Mass | 585.192 |
| Elemental Analysis | C, 59.48; H, 4.99; F, 6.49; N, 7.18; O, 21.86 |
| CAS # | 1025097-10-2 |
| Related CAS # | 1025097-10-2 |
| PubChem CID | 44242317 |
| Appearance | White to light yellow solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 832.6±65.0 °C at 760 mmHg |
| Flash Point | 457.4±34.3 °C |
| Vapour Pressure | 0.0±3.2 mmHg at 25°C |
| Index of Refraction | 1.660 |
| LogP | 1.73 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 42 |
| Complexity | 1100 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | FC1C=C2C(C(C(=O)O)=CN(C2=CC=1N1CCC(COC2C=CC(=CC=2F)N2C(=O)O[C@@H](CO)C2)(CC1)O)C1CC1)=O |
| InChi Key | XWFCFMXQTBGXQW-GOSISDBHSA-N |
| InChi Code | InChI=1S/C29H29F2N3O8/c30-21-10-19-23(33(16-1-2-16)13-20(26(19)36)27(37)38)11-24(21)32-7-5-29(40,6-8-32)15-41-25-4-3-17(9-22(25)31)34-12-18(14-35)42-28(34)39/h3-4,9-11,13,16,18,35,40H,1-2,5-8,12,14-15H2,(H,37,38)/t18-/m1/s1 |
| Chemical Name | 1-Cyclopropyl-6-fluoro-7-[4-({2-fluoro-4-[(5R)-5-(hydroxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenoxy}methyl)-4-hydroxypiperidin-1-yl]-4-oxo-1,4-dihydroquinolin-3-carboxylic acid |
| Synonyms | ACT-179811; ACT 179811; ACT179811; Cadazolid. |
| 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) |
Biological Activity
| Targets | Oxazolidinone |
| ln Vitro | A novel antibiotic called cadezolide is being developed to treat diarrhea caused by Clostridium difficile[1]. All strains of Clostridium difficile, including those resistant to moxifloxacin and linezolid, are susceptible to the effects of cadazolid (MIC90 0.125, range 0.03-0.25 mg/L). In comparison to moxifloxacin, linezolid, metronidazole, and vancomycin, the cadazolid geometric mean MIC is 152-fold, 16-fold, 9-fold, and 7-fold lower, respectively. With no sign of recurrence, both cadazolid dosing regimens quickly lower cytotoxin and Clostridium difficile viable counts. Cadazolid levels last for 14 days after dosage, remaining 50–100 times supra-MIC. With the exception of bifidobacteria, cadezolides only slightly inhibit the counts of Lactobacillus spp. and members of the Bacteroides fragilis group of the enumerated gut microflora. There is no proof that strains resistant to linezolid, quinolones, or cadazolid have been chosen[2]. |
| ln Vivo | If taken twice daily for ten days, cadmiolid up to 3000 mg is well tolerated. There is no correlation found between adverse events and treatment duration or dosage; headaches are the most frequent adverse event. Cadazolid plasma concentrations are minimal. No plasma concentrations greater than 3.3 ng/mL or greater than 6.9 ng/mL following ten days of consecutive doses are seen. After a single 300 mg dose, food increased the mean Cmax from 0.73 to 1.87 ng/mL and the mean AUC0–t from 3.13 to 15.69 ng·h/mL. Less than dose-proportional increases in systemic exposure to cadazolid occur across doses. 81.0%–93.5% is the average cumulative faecal recovery. Less than 0.015% of unchanged compound is recovered in the urine[1]. |
| References |
[1]. Cadazolid, a novel antibiotic with potent activity against Clostridium difficile: safety, tolerability and pharmacokinetics in healthy subjects following single and multiple oral doses. J Antimicrob Chemother. 2014 Mar;69(3):706-14. [2]. In vitro activity of cadazolid against clinically relevant Clostridium difficile isolates and in an in vitro gut model of C. difficile infection. J Antimicrob Chemother. 2014 Mar;69(3):697-705. [3]. Seiler P, Enderlin-Paput M, Pfaff P, Weiss M, Ritz D, Clozel M, Locher HH. Cadazolid does not promote intestinal colonization of vancomycin-resistant enterococci in mice. Antimicrob Agents Chemother. 2015 Oct 26. pii: AAC.01923-15. [Epub ahead of print] PubMed PMID: 26503650 |
| Additional Infomation |
Cadazolid has been used in trials studying the treatment of Clostridium Difficile Infection. Cadazolid is an oxazolidinone-type antibiotic, with activity against gram-positive bacteria, including Clostridium difficile. Although the exact mode of action through which cadazolid exerts its effect has yet to be fully elucidated, upon administration, this agent inhibits bacterial protein synthesis and leads to bacterial cell death. Drug Indication Treatment of Clostridium difficile infection |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~170.78 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 10% DMSO+90% (20% SBE-β-CD in Saline): ≥ 2.5 mg/mL (4.27 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7078 mL | 8.5388 mL | 17.0777 mL | |
| 5 mM | 0.3416 mL | 1.7078 mL | 3.4155 mL | |
| 10 mM | 0.1708 mL | 0.8539 mL | 1.7078 mL |