Cadazolid

Research use only, not for human use.

Cadazolid is an oxazolidinone-type antibiotic, with activity against gram-positive bacteria, including Clostridium difficile.

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.(In Vitro):Cadazolid is a new antibiotic in development for the treatment of Clostridium difficile-associated diarrhea. Cadazolid is active against all (including linezolid- and moxifloxacin-resistant) Clostridium difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC is 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduce Clostridium difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persists at 50-100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora is limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts are unaffected. There is no evidence for selection of strains resistant to cadazolid, quinolones or linezolid. (In Vivo):Cadazolid is well tolerated up to 3000 mg given twice daily for 10 days. The most common adverse event is headache, with no observed relationship between dose or treatment duration and adverse events. Plasma concentrations of cadazolid are low. No plasma concentrations >3.3 ng/mL are observed after single doses or >6.9 ng/mL after 10 days of multiple doses. Food increased the mean Cmax from 0.73 to 1.87 ng/mL and mean AUC0–t from 3.13 to 15.69 ng·h/mL after a single 300 mg dose. The increase in systemic exposure to cadazolid across doses is less than dose-proportional. The mean cumulative faecal recovery is 81.0%–93.5%. Urinary recovery of unchanged compound is less than 0.015%.

Cadazolid is a new antibiotic in development for the treatment of Clostridium difficile-associated diarrhea. Cadazolid is active against all (including linezolid- and moxifloxacin-resistant) Clostridium difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC is 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduce Clostridium difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persists at 50-100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora is limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts are unaffected. There is no evidence for selection of strains resistant to cadazolid, quinolones or linezolid.

Cadazolid is well tolerated up to 3000 mg given twice daily for 10 days. The most common adverse event is headache, with no observed relationship between dose or treatment duration and adverse events. Plasma concentrations of cadazolid are low. No plasma concentrations >3.3 ng/mL are observed after single doses or >6.9 ng/mL after 10 days of multiple doses. Food increased the mean Cmax from 0.73 to 1.87 ng/mL and mean AUC0–t from 3.13 to 15.69 ng·h/mL after a single 300 mg dose. The increase in systemic exposure to cadazolid across doses is less than dose-proportional. The mean cumulative faecal recovery is 81.0%–93.5%. Urinary recovery of unchanged compound is less than 0.015%.

ACT-179811 | Cadazolid.

Others

Other Targets

Others

——

——

1025097-10-2

585.19

C29H29F2N3O8

>98% (HPLC)

DMSO : ≥ 150 mg/mL 256.17 mM

c1c(c(cc2c1n(cc(c2=O)C(=O)O)C1CC1)F)N1CCC(CC1)(COc1c(cc(cc1)N1C[C@@H](OC1=O)CO)F)O

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

(-20℃)

With Ice Pack

≥ 2 years