Cadazolid | CAS#1025097-10-2 | protein synthesis inhibitor

MedKoo Cat#: 319542 | Name: Cadazolid

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Cadazolid

CAS#1025097-10-2

Theoretical Analysis

MedKoo Cat#: 319542

Name: Cadazolid

CAS#: 1025097-10-2

Chemical Formula: C29H29F2N3O8

Exact Mass: 585.1923

Molecular Weight: 585.56

Elemental Analysis: C, 59.48; H, 4.99; F, 6.49; N, 7.18; O, 21.86

Price and Availability

Size	Price	Availability
10mg	USD 450.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
200mg	USD 2,650.00	2 Weeks
1g	USD 5,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

ACT-179811; ACT 179811; ACT179811; Cadazolid.

IUPAC/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

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

SMILES Code

O=C(C1=CN(C2CC2)C3=C(C=C(F)C(N4CCC(O)(COC5=CC=C(N6C(O[C@@H](CO)C6)=O)C=C5F)CC4)=C3)C1=O)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Cadazolid (ACT-179811) is a new oxazolidinone antibiotic with potent activity against Clostridium difficile.

In vitro activity:

Cadazolid was active against all (including linezolid- and moxifloxacin-resistant) C. difficile strains (MIC90 0.125, range 0.03-0.25 mg/L). The cadazolid geometric mean MIC was 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduced C. difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persisted at 50-100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora was limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts were unaffected. There was no evidence for selection of strains resistant to cadazolid, quinolones or linezolid. Reference: J Antimicrob Chemother. 2014 Mar;69(3):697-705. https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkt411

In vivo activity:

Cadazolid dose dependently prevented mortality and diarrhea when given to presensitized and C. difficile-infected C57BL/6 mice (Fig. 5). Dose-dependent efficacy was observed during and after treatment time and was reproducible between experiments. In 17 pooled independent experiments, the overall survival rates of mice treated with vehicle or cadazolid at doses of 0.1, 1, and 10 mg/kg were 18, 47, 97, and 100%, respectively, after the treatment period (day 5), while the corresponding values were 12, 40, 92, and 88%, respectively, at day 18 postinfection (Table 2). According to Cox proportional hazards regression analysis, cadazolid decreased the risk of death of infected mice during the 18-day monitoring period by 56, 96, and 95%, respectively, indicating a significant sustained treatment effect compared to vehicle-treated mice (P < 0.001 for all three dose groups). Overall, 0.1 mg/kg cadazolid was significantly less protective than 1 mg/kg and 10 mg/kg (P < 0.001), while 1 mg/kg was not significantly different from 10 mg/kg (P = 0.7). In three studies, cadazolid was compared to vancomycin side by side, and the pooled overall survival rates were similar at the same doses (Table 2). Reference: Antimicrob Agents Chemother. 2014;58(2):892-900. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24277020/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	170.78

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 585.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Chilton CH, Crowther GS, Baines SD, Todhunter SL, Freeman J, Locher HH, Athanasiou A, Wilcox MH. 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. doi: 10.1093/jac/dkt411. Epub 2013 Oct 14. PMID: 24128668. 2. Locher HH, Seiler P, Chen X, Schroeder S, Pfaff P, Enderlin M, Klenk A, Fournier E, Hubschwerlen C, Ritz D, Kelly CP, Keck W. In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother. 2014;58(2):892-900. doi: 10.1128/AAC.01830-13. Epub 2013 Nov 25. PMID: 24277020; PMCID: PMC3910819.

In vivo protocol:

1: Endres BT, Bassères E, Alam MJ, Garey KW. Cadazolid for the treatment of Clostridium difficile. Expert Opin Investig Drugs. 2017 Apr;26(4):509-514. doi: 10.1080/13543784.2017.1304538. PMID: 28286992. 2: Kali A, Charles MV, Srirangaraj S. Cadazolid: A new hope in the treatment of Clostridium difficile infection. Australas Med J. 2015 Aug 31;8(8):253-62. doi: 10.4066/AMJ.2015.2441. PMID: 26392822; PMCID: PMC4560895. 3: Muhammad A, Simcha W, Rawish F, Sabih R, Albert E, Ali N. Cadazolid vs Vancomycin for the Treatment of Clostridioides difficile Infection: Systematic Review with Meta-analysis. Curr Clin Pharmacol. 2020;15(1):4-10. doi: 10.2174/1574884714666190802124301. PMID: 31376824; PMCID: PMC7366008. 4: Ooijevaar RE, van Beurden YH, Terveer EM, Goorhuis A, Bauer MP, Keller JJ, Mulder CJJ, Kuijper EJ. Update of treatment algorithms for Clostridium difficile infection. Clin Microbiol Infect. 2018 May;24(5):452-462. doi: 10.1016/j.cmi.2017.12.022. Epub 2018 Jan 6. PMID: 29309934. 5: Gerding DN, Cornely OA, Grill S, Kracker H, Marrast AC, Nord CE, Talbot GH, Buitrago M, Gheorghe Diaconescu I, Murta de Oliveira C, Preotescu L, Pullman J, Louie TJ, Wilcox MH. Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. Lancet Infect Dis. 2019 Mar;19(3):265-274. doi: 10.1016/S1473-3099(18)30614-5. Epub 2019 Jan 29. PMID: 30709665. 6: 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;60(1):628-31. doi: 10.1128/AAC.01923-15. PMID: 26503650; PMCID: PMC4704215. 7: Baldoni D, Gutierrez M, Timmer W, Dingemanse J. 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. doi: 10.1093/jac/dkt401. Epub 2013 Oct 8. PMID: 24106141. 8: Peng Z, Ling L, Stratton CW, Li C, Polage CR, Wu B, Tang YW. Advances in the diagnosis and treatment of Clostridium difficile infections. Emerg Microbes Infect. 2018 Feb 7;7(1):15. doi: 10.1038/s41426-017-0019-4. PMID: 29434201; PMCID: PMC5837143. 9: Skinner K, Birchall S, Corbett D, Thommes P, Locher HH. Time-kill kinetics of cadazolid and comparator antibacterial agents against different ribotypes of Clostridium difficile. J Med Microbiol. 2018 Sep;67(9):1402-1409. doi: 10.1099/jmm.0.000808. Epub 2018 Jul 27. PMID: 30052178. 10: Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev. 2017 Mar 3;3(3):CD004610. doi: 10.1002/14651858.CD004610.pub5. PMID: 28257555; PMCID: PMC6464548. 11: Gehin M, Desnica B, Dingemanse J. Minimal systemic and high faecal exposure to cadazolid in patients with severe Clostridium difficile infection. Int J Antimicrob Agents. 2015 Nov;46(5):576-81. doi: 10.1016/j.ijantimicag.2015.07.015. Epub 2015 Sep 3. PMID: 26419191. 12: Chilton CH, Crowther GS, Baines SD, Todhunter SL, Freeman J, Locher HH, Athanasiou A, Wilcox MH. 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. doi: 10.1093/jac/dkt411. Epub 2013 Oct 14. PMID: 24128668. 13: Scaiola A, Leibundgut M, Boehringer D, Caspers P, Bur D, Locher HH, Rueedi G, Ritz D. Structural basis of translation inhibition by cadazolid, a novel quinoxolidinone antibiotic. Sci Rep. 2019 Apr 4;9(1):5634. doi: 10.1038/s41598-019-42155-4. PMID: 30948752; PMCID: PMC6449356. 14: Boyanova L, Markovska R, Mitov I. Multidrug resistance in anaerobes. Future Microbiol. 2019 Aug;14:1055-1064. doi: 10.2217/fmb-2019-0132. PMID: 31469008. 15: Locher HH, Seiler P, Chen X, Schroeder S, Pfaff P, Enderlin M, Klenk A, Fournier E, Hubschwerlen C, Ritz D, Kelly CP, Keck W. In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother. 2014;58(2):892-900. doi: 10.1128/AAC.01830-13. Epub 2013 Nov 25. PMID: 24277020; PMCID: PMC3910819. 16: Gerding DN, Hecht DW, Louie T, Nord CE, Talbot GH, Cornely OA, Buitrago M, Best E, Sambol S, Osmolski JR, Kracker H, Locher HH, Charef P, Wilcox M. Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection. J Antimicrob Chemother. 2016 Jan;71(1):213-9. doi: 10.1093/jac/dkv300. Epub 2015 Oct 3. PMID: 26433782; PMCID: PMC4681371. 17: Louie T, Nord CE, Talbot GH, Wilcox M, Gerding DN, Buitrago M, Kracker H, Charef P, Cornely OA. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection. Antimicrob Agents Chemother. 2015 Oct;59(10):6266-73. doi: 10.1128/AAC.00504-15. Epub 2015 Jul 27. PMID: 26248357; PMCID: PMC4576054. 18: Locher HH, Caspers P, Bruyère T, Schroeder S, Pfaff P, Knezevic A, Keck W, Ritz D. Investigations of the mode of action and resistance development of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother. 2014;58(2):901-8. doi: 10.1128/AAC.01831-13. Epub 2013 Nov 25. PMID: 24277035; PMCID: PMC3910891. 19: Rashid MU, Lozano HM, Weintraub A, Nord CE. In vitro activity of cadazolid against Clostridium difficile strains isolated from primary and recurrent infections in Stockholm, Sweden. Anaerobe. 2013 Apr;20:32-5. doi: 10.1016/j.anaerobe.2013.02.003. Epub 2013 Feb 26. PMID: 23454525. 20: Petrosillo N, Granata G, Cataldo MA. Novel Antimicrobials for the Treatment of Clostridium difficile Infection. Front Med (Lausanne). 2018 Apr 16;5:96. doi: 10.3389/fmed.2018.00096. PMID: 29713630; PMCID: PMC5911476.