Rezafungin (Biafungin; Rezzayo) is a novel, broad-spectrum, and long-lasting echinocandin with antifungal activity against Candida spp., Aspergillus spp., and Pneumocystis spp. It acts as a 1,3-β-D-glucan synthase inhibitor. In Mar 2023, it has been approved by FDA for the treatment of Candidiasis.
Physicochemical Properties
| Molecular Formula | C63H85N8O17 |
| Molecular Weight | 1226.3924176693 |
| Exact Mass | 1225.603 |
| CAS # | 1396640-59-7 |
| Related CAS # | Rezafungin acetate;1631754-41-0; 1396640-59-7 (cation) ; 1396640-60-0 (TFA) |
| PubChem CID | 78318119 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2.9 |
| Hydrogen Bond Donor Count | 13 |
| Hydrogen Bond Acceptor Count | 17 |
| Rotatable Bond Count | 18 |
| Heavy Atom Count | 88 |
| Complexity | 2300 |
| Defined Atom Stereocenter Count | 15 |
| SMILES | CCCCCOC1=CC=C(C=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C(=O)N[C@H]4C[C@H]([C@H](NC(=O)[C@@H]5[C@H]([C@H](CN5C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]6C[C@H](CN6C(=O)[C@@H](NC4=O)[C@@H](C)O)O)[C@@H]([C@H](C7=CC=C(C=C7)O)O)O)[C@@H](C)O)C)O)OCC[N+](C)(C)C)O |
| InChi Key | LNFCWEXGZIEGJW-TXSVMFMRSA-O |
| InChi Code | InChI=1S/C63H84N8O17/c1-8-9-10-28-87-45-25-21-40(22-26-45)38-13-11-37(12-14-38)39-15-17-42(18-16-39)56(80)64-46-31-48(76)61(88-29-27-71(5,6)7)68-60(84)52-53(77)34(2)32-70(52)63(86)50(36(4)73)66-59(83)51(55(79)54(78)41-19-23-43(74)24-20-41)67-58(82)47-30-44(75)33-69(47)62(85)49(35(3)72)65-57(46)81/h11-26,34-36,44,46-55,61,72-73,75-79H,8-10,27-33H2,1-7H3,(H5-,64,65,66,67,68,74,80,81,82,83,84)/p+1/t34-,35+,36+,44+,46-,47-,48+,49-,50-,51-,52-,53-,54-,55-,61+/m0/s1 |
| Chemical Name | 2-[[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,25-trihydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-18-[[4-[4-(4-pentoxyphenyl)phenyl]benzoyl]amino]-1,4,7,13,16,22-hexazatricyclo[22.3.0.09,13]heptacosan-21-yl]oxy]ethyl-trimethylazanium |
| Synonyms | Rezafungin; rezafungin acetate; 1631754-41-0; Rezafungin (acetate); acetate de rezafungine; acetato de rezafungina; Biafungin; Rezzayo |
| 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 | 1,3-β-D-glucan synthase enzyme complex |
| ln Vitro | Rezafungin is an echinocandin antifungal drug. It inhibits the 1,3-β-D-glucan synthase enzyme complex present in the cell walls of fungi, responsible for the formation of 1,3-β-D-glucan. Since 1,3-β-D-glucan is an essential component of fungal cell walls, rezafungin disrupts the cell wall of fungal species, including _Candida_ spp., and acts as a concentration-dependent _in vitro_ fungicidal. Mammalian cells do not express β-1-3-glucan synthase; therefore, the action of rezafungin is specific to fungi. Rezafungin is a member of the family of echinocandins that inhibits 1,3-beta-D-glucan synthase. |
| ln Vivo | In a mouse infection model, rezafungin (Biafungin) has demonstrated strong in vivo prophylaxis against Pneumocystis jiroveci [1]. |
| Animal Protocol |
Animal/Disease Models: C3H/HeN mice [1] Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 6 days. Experimental Results: The burden of cell nuclei and ascus was Dramatically diminished. |
| ADME/Pharmacokinetics |
Absorption Between 50 mg (0.125 times the approved maximum recommended loading dose) and 400 mg and with single or multiple doses, the Cmax and AUC of rezafungin increase in a dose-proportional manner. In patients with candidemia and invasive candidias given an initial 400 mg loading dose of rezafungin, followed by a 200 mg dose once weekly, the Cmax, AUC from time zero to 168 hours post-dose (AUC0-168) and Cmin on day 1 were 19.2 mcg/mL, 827 mcg⋅h/mL and 2.4 mcg/mL, respectively. In the same group of patients, the Cmax, AUC0-168 and Cmin on day 15 were 11.8 mcg/mL, 667 mcg⋅h/mL and 2.2 mcg/mL, respectively. Compared to healthy subjects, the AUC0-168 and Cmax were 30% and 19% lower in patients with candidemia. Age, sex, race, weight and hepatic impairment did not have a clinically significant effect on rezafungin pharmacokinetics. Route of Elimination Rezafungin is mainly eliminated through fecal excretion. In healthy subjects, 74.3% was recovered in feces primarily as rezafungin, while 25.7% was recovered in urine primarily as inactive metabolites of rezafungin. Volume of Distribution Rezafungin has a volume of distribution of 67 L. Clearance Rezafungin has an elimination clearance of 0.35 L/hr. Protein Binding Rezafungin is highly protein bound. Protein binding goes from 87.5% to 93.6% in patients, and from 95.6% to >98.6% in healthy adults. Metabolism / Metabolites Rezafungin is metabolized by hydroxylation of the terphenyl, pentyl ether side chain, to form three hydroxylated metabolite isomers: 2’-, 3′-, or 4’-hydroxylpentyl rezafungin. Rezafungin can also be metabolized through a reaction that involves the loss of the pentyl group via O-dealkylation, forming despentyl-rezafungin. There is minimal subsequent conjugation (sulfation) of the hydroxyl metabolites. Rezafungin is not metabolized in the liver and is not expected to be a clinically relevant substrate of CYP450 enzymes. Biological Half-Life Rezafungin has a terminal half-life of 152 hours. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of rezafungin during breastfeeding. Because rezafungin is about 90% bound to plasma proteins and has poor oral bioavailability, it is unlikely to reach the milk and be absorbed by the infant. If rezafungin is required by the mother, it is not a reason to discontinue breastfeeding. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
[1]. Melanie Cushion, et al. Rezafungin Prophylactic Efficacy in a Mouse Model of Pneumocystis Pneumonia. VOLUME 25, ISSUE 3, SUPPLEMENT, S366, MARCH 01, 2019. [2]. Sofjan AK, et al. Rezafungin (CD101), a next-generation echinocandin: A systematic literature review and assessment of possible place in therapy. J Glob Antimicrob Resist. 2018 Sep;14:58-64. |
| Additional Infomation |
Rezafungin is a member of the family of echinocandins that inhibits 1,3-beta-D-glucan synthase. It is developed by Cidara Therapeutics and approved for the treatment of candidaemia and invasive candidiasis in patients aged >= 18 years who have limited or no alternative treatment options. It is an echinocandin, a quaternary ammonium ion, an antibiotic antifungal drug, an azamacrocycle, a homodetic cyclic peptide and an aromatic ether. Rezafungin is an Echinocandin Antifungal. Rezafungin is a next-generation, semi-synthetic, cyclic lipopeptide and echinocandin derivative, with potential antifungal activity. Upon administration, rezafungin inhibits the fungal specific enzyme 1,3-beta-D-glucan synthase, which is essential for fungal cell wall synthesis, and results in decreased synthesis of beta(1,3)-D-glucan. This weakens the fungal cell wall thereby causing osmotic lysis, fungal cell wall rupture and fungal cell death. See also: Rezafungin (annotation moved to). |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 : PEG300 ：Tween 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). 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 : PEG300：Tween 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). 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 | 0.8154 mL | 4.0770 mL | 8.1540 mL | |
| 5 mM | 0.1631 mL | 0.8154 mL | 1.6308 mL | |
| 10 mM | 0.0815 mL | 0.4077 mL | 0.8154 mL |