WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H317107
CAS#: 946075-13-4 (sulfate)
Description: Isavuconazole (BAL4815; trade name Cresemba) is a triazole antifungal drug. Its prodrug, isavuconazonium sulfate (BAL8557), was granted approval by the U.S. Food and Drug Administration (FDA) on March 6, 2015. Isavuconazole has been approved for treatment of invasive aspergillosis and invasive mucormycosis in adults ages 18 years and older. Both infections are caused by mold and fungi common to the environment, and occur in individuals who are immunosuppressed or have other complicating conditions, such as diabetes or lung disease.
Hodoodo Cat#: H317107
Name: Isavuconazonium sulfate
CAS#: 946075-13-4 (sulfate)
Chemical Formula: C35H36F2N8O9S2
Exact Mass: 0.00
Molecular Weight: 814.840
Elemental Analysis: C, 51.59; H, 4.45; F, 4.66; N, 13.75; O, 17.67; S, 7.87
Related CAS #: 338990-84-4 (chloride) 497235-79-7 (chloride HCl) 742049-41-8 (cation) 946075-13-4 (sulfate)
Synonym: BAL8557; BAL-8557; BAL 8557; isavuconazole; Isavuconazonium sulfate; brand name: Cresemba.
IUPAC/Chemical Name: 1-((2R,3R)-3-(4-(4-cyanophenyl)thiazol-2-yl)-2-(2,5-difluorophenyl)-2-hydroxybutyl)-4-(1-((methyl(3-(((methylglycyl)oxy)methyl)pyridin-2-yl)carbamoyl)oxy)ethyl)-1H-1,2,4-triazol-4-ium hydrogen sulfate
InChi Key: LWXUIUUOMSMZKJ-KLFWAVJMSA-M
InChi Code: InChI=1S/C35H35F2N8O5S.H2O4S/c1-22(33-42-30(18-51-33)25-9-7-24(15-38)8-10-25)35(48,28-14-27(36)11-12-29(28)37)19-45-21-44(20-41-45)23(2)50-34(47)43(4)32-26(6-5-13-40-32)17-49-31(46)16-39-3;1-5(2,3)4/h5-14,18,20-23,39,48H,16-17,19H2,1-4H3;(H2,1,2,3,4)/q+1;/p-1/t22-,23?,35+;/m0./s1
SMILES Code: C[C@@H](C1=NC(=CS1)C2=CC=C(C=C2)C#N)[C@](CN3C=[N+](C=N3)C(C)OC(=O)N(C)C4=C(C=CC=N4)COC(=O)CNC)(C5=C(C=CC(=C5)F)F)O.OS(=O)(=O)[O-]
Appearance: Solid powder
Purity: >97% (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:
| Biological target: | Isavuconazonium sulfate (BAL8557-002), the prodrug of the active triazole Isavuconazole, is an antifungal agent. |
| In vitro activity: | Treatment with isavuconazole at 45 nM likewise resulted in significant growth inhibition and cell death (Fig. 4C). At 24 h, isavuconazole-treated trophozoites began showing signs of cellular rounding compared to the DMSO-treated trophozoites. At 36 and 48 h, the trophozoites completely rounded and detached from the bottom of the culture plate. There was also an appreciable increase in cellular granularity and no significant cellular proliferation between 36 and 48 h (Fig. 4C). Furthermore, the medium of isavuconazole-treated trophozoites displayed more cellular debris and membrane components than that of 16.6 μM chlorhexidine. Reference: Antimicrob Agents Chemother. 2020 May; 64(5): e02223-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179639/ |
| In vivo activity: | To determine the potential mechanisms by which isavuconazole improves disease outcomes, this study assessed its impact on two hallmark characteristics of A. fumigatus endophthalmitis, fungal burden and inflammatory cytokines, in treated and untreated A. fumigatus-infected mice. All routes of treatment with isavuconazole reduced fungal burden in A. fumigatus-infected mice relative to that of those that were untreated; however, i.v. administration was the least effective route (Fig. 4A). This study also assessed the effect of isavuconazole treatment on ocular inflammation using an enzyme-linked immunosorbent assay (ELISA) consisting of inflammatory mediators. While elevated levels of inflammatory cytokines (e.g., tumor necrosis factor α [TNF-α], interleukin 1β [IL-1β], and IL-6) were observed in the eyes of untreated A. fumigatus-infected mice, cytokine levels were greatly reduced in A. fumigatus-infected mice that received isavuconazole treatment (Fig. 4B to D). Reference: Antimicrob Agents Chemother. 2018 Nov; 62(11): e01537-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201095/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 93.3 | 114.55 | |
| DMSO:PBS (pH 7.2) (1:5) | 0.2 | 0.20 | |
| Ethanol | 10.0 | 12.27 |
The following data is based on the product molecular weight 814.84 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: | 1. Shing B, Singh S, Podust LM, McKerrow JH, Debnath A. The Antifungal Drug Isavuconazole Is both Amebicidal and Cysticidal against Acanthamoeba castellanii. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02223-19. doi: 10.1128/AAC.02223-19. PMID: 32094126; PMCID: PMC7179639. 2. Pfaller MA, Rhomberg PR, Wiederhold NP, Gibas C, Sanders C, Fan H, Mele J, Kovanda LL, Castanheira M. In Vitro Activity of Isavuconazole against Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01230-18. doi: 10.1128/AAC.01230-18. PMID: 30061288; PMCID: PMC6153788. 3. Guest JM, Singh PK, Revankar SG, Chandrasekar PH, Kumar A. Isavuconazole for Treatment of Experimental Fungal Endophthalmitis Caused by Aspergillus fumigatus. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01537-18. doi: 10.1128/AAC.01537-18. PMID: 30201814; PMCID: PMC6201095. 4. Schmitt-Hoffmann AH, Kato K, Townsend R, Potchoiba MJ, Hope WW, Andes D, Spickermann J, Schneidkraut MJ. Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01292-17. doi: 10.1128/AAC.01292-17. PMID: 28971866; PMCID: PMC5700325. |
| In vitro protocol: | 1. Shing B, Singh S, Podust LM, McKerrow JH, Debnath A. The Antifungal Drug Isavuconazole Is both Amebicidal and Cysticidal against Acanthamoeba castellanii. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02223-19. doi: 10.1128/AAC.02223-19. PMID: 32094126; PMCID: PMC7179639. 2. Pfaller MA, Rhomberg PR, Wiederhold NP, Gibas C, Sanders C, Fan H, Mele J, Kovanda LL, Castanheira M. In Vitro Activity of Isavuconazole against Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01230-18. doi: 10.1128/AAC.01230-18. PMID: 30061288; PMCID: PMC6153788. |
| In vivo protocol: | 1. Guest JM, Singh PK, Revankar SG, Chandrasekar PH, Kumar A. Isavuconazole for Treatment of Experimental Fungal Endophthalmitis Caused by Aspergillus fumigatus. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e01537-18. doi: 10.1128/AAC.01537-18. PMID: 30201814; PMCID: PMC6201095. 2. Schmitt-Hoffmann AH, Kato K, Townsend R, Potchoiba MJ, Hope WW, Andes D, Spickermann J, Schneidkraut MJ. Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01292-17. doi: 10.1128/AAC.01292-17. PMID: 28971866; PMCID: PMC5700325. |
1: Regella VRPS, Subramanian VC, Bhetanabhotla SS. Identification and structural characterization of four novel degradation products and a process impurity of isavuconazonium sulfate for injection formulation bulk by LC-ESI-QTOF-MS/MS. Eur J Mass Spectrom (Chichester). 2019 Nov 10:1469066719884402. doi: 10.1177/1469066719884402. [Epub ahead of print] PubMed PMID: 31707848.
2: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548643/ PubMed PMID: 31643955.
3: Van Matre ET, Evans SL, Mueller SW, MacLaren R, Fish DN, Kiser TH. Comparative evaluation of isavuconazonium sulfate, voriconazole, and posaconazole for the management of invasive fungal infections in an academic medical center. Ann Clin Microbiol Antimicrob. 2019 Mar 20;18(1):13. doi: 10.1186/s12941-019-0311-3. PubMed PMID: 30894179; PubMed Central PMCID: PMC6427894.
4: Adamsick ML, Elshaboury RH, Gift T, Mansour MK, Kotton CN, Gandhi RG. Therapeutic drug concentrations of isavuconazole following the administration of isavuconazonium sulfate capsules via gastro-jejunum tube: A case report. Transpl Infect Dis. 2019 Apr;21(2):e13048. doi: 10.1111/tid.13048. Epub 2019 Jan 29. PubMed PMID: 30636363.
5: Pfaller MA, Rhomberg PR, Castanheira M. Direct in vitro comparison of the prodrug isavuconazonium sulfate with the isavuconazole active compound against Aspergillus spp. and 2 rare moulds. Diagn Microbiol Infect Dis. 2018 Sep;92(1):43-45. doi: 10.1016/j.diagmicrobio.2018.04.005. Epub 2018 Apr 13. PubMed PMID: 29735424.
6: Schmitt-Hoffmann AH, Kato K, Townsend R, Potchoiba MJ, Hope WW, Andes D, Spickermann J, Schneidkraut MJ. Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats. Antimicrob Agents Chemother. 2017 Nov 22;61(12). pii: e01292-17. doi: 10.1128/AAC.01292-17. Print 2017 Dec. PubMed PMID: 28971866; PubMed Central PMCID: PMC5700325.
7: Townsend R, Kato K, Hale C, Kowalski D, Lademacher C, Yamazaki T, Akhtar S, Desai A. Two Phase 1, Open-Label, Mass Balance Studies to Determine the Pharmacokinetics of (14) C-Labeled Isavuconazonium Sulfate in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2018 Feb;7(2):207-216. doi: 10.1002/cpdd.376. Epub 2017 Jul 27. PubMed PMID: 28750160; PubMed Central PMCID: PMC5811773.
8: So W, Kim L, Thabit AK, Nicolau DP, Kuti JL. Physical compatibility of isavuconazonium sulfate with select i.v. drugs during simulated Y-site administration. Am J Health Syst Pharm. 2017 Jan 1;74(1):e55-e63. doi: 10.2146/ajhp150733. Epub 2016 Dec 22. PubMed PMID: 28007722.
9: Murrell D, Bossaer JB, Carico R, Harirforoosh S, Cluck D. Isavuconazonium sulfate: a triazole prodrug for invasive fungal infections. Int J Pharm Pract. 2017 Feb;25(1):18-30. doi: 10.1111/ijpp.12302. Epub 2016 Aug 29. Review. PubMed PMID: 27569742.
10: Kovanda LL, Maher R, Hope WW. Isavuconazonium sulfate: a new agent for the treatment of invasive aspergillosis and invasive mucormycosis. Expert Rev Clin Pharmacol. 2016 Jul;9(7):887-97. doi: 10.1080/17512433.2016.1185361. Epub 2016 May 21. Review. PubMed PMID: 27160418.
11: Isavuconazonium sulfate (Cresemba)--a new antifungal. Med Lett Drugs Ther. 2016 Mar 14;58(1490):37-8. Review. PubMed PMID: 26963156.
12: Walker RC, Zeuli JD, Temesgen Z. Isavuconazonium sulfate for the treatment of fungal infection. Drugs Today (Barc). 2016 Jan;52(1):7-16. doi: 10.1358/dot.2016.52.1.2404002. Review. PubMed PMID: 26937491.
13: Hussar DA, Friedman J. Ceftazidime pentahydrate/avibactam sodium, Isavuconazonium sulfate, and Daclatasvir dihydrochloride. J Am Pharm Assoc (2003). 2016 Jan;56(1):100-3. doi: 10.1016/j.japh.2015.12.003. PubMed PMID: 26802929.
14: McCormack PL. Isavuconazonium: first global approval. Drugs. 2015 May;75(7):817-22. doi: 10.1007/s40265-015-0398-6. Review. PubMed PMID: 25902926.
15: Traynor K. Isavuconazonium sulfate approved for invasive fungal infections. Am J Health Syst Pharm. 2015 Apr 15;72(8):592. doi: 10.2146/news150027. PubMed PMID: 25825173.
