Physicochemical Properties
| Molecular Weight | 959.188g/mol |
| Exact Mass | 958.551 |
| CAS # | 104138-64-9 |
| PubChem CID | 52918379 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 8 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 25 |
| Heavy Atom Count | 68 |
| Complexity | 617 |
| Defined Atom Stereocenter Count | 6 |
| SMILES | CCCCCCCC(=O)N[C@H](CN1CCCC1)[C@@H](C2=CC3=C(C=C2)OCCO3)O.CCCCCCCC(=O)N[C@H](CN1CCCC1)[C@@H](C2=CC3=C(C=C2)OCCO3)O.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O |
| InChi Key | KUBARPMUNHKBIQ-VTHUDJRQSA-N |
| InChi Code | InChI=1S/2C23H36N2O4.C4H6O6/c2*1-2-3-4-5-6-9-22(26)24-19(17-25-12-7-8-13-25)23(27)18-10-11-20-21(16-18)29-15-14-28-20;5-1(3(7)8)2(6)4(9)10/h2*10-11,16,19,23,27H,2-9,12-15,17H2,1H3,(H,24,26);1-2,5-6H,(H,7,8)(H,9,10)/t2*19-,23-;1-,2-/m111/s1 |
| Chemical Name | N-[(1R,2R)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-pyrrolidin-1-ylpropan-2-yl]octanamide;(2R,3R)-2,3-dihydroxybutanedioic acid |
| 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
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion A dose of agalsidase alfa in non end stage renal disease patients reaches a Cmax of 3710 ± 855 U/mL with an AUC of 256,958 ± 63,499 min\*U/mL. After nonspecific proteolysis, the amino acids from protein drugs are reused for protein synthesis or further broken down and eliminated by the kidneys. The volume of distribution at steady state in non end stage renal disease patients was approximately 17% of body weight regardless of sex. The clearance for doses of 0.007-0.2 mg/kg were 2.66 mL/min/kg for males and 2.10 mL/min/kg for females. Metabolism / Metabolites Data regarding the metabolism of agalsidase alfa is not readily available. However, protein drugs are expected to be degraded by proteases and other catalytic enzymes to smaller peptides and amino acids. Biological Half-Life The elimination half life was 108 ± 17 minutes for males and 89 ± 28 minutes for females. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because there is no published experience with eliglustat during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ 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. Protein Binding Agalsidase alfa is not expected to be protein bound in circulation. |
| References | [1]. Keating GM. Agalsidase alfa: a review of its use in the management of Fabry disease. BioDrugs. 2012 Oct 1;26(5):335-54. |
| Additional Infomation |
Eliglustat tartrate is a tartrate that is the hemitartrate salt of eliglustat. A ceramide glucosyltransferase inhibitor used (as its tartrate salt) for treatment of Gaucher's disease. It has a role as an EC 2.4.1.80 (ceramide glucosyltransferase) inhibitor. It contains an eliglustat(1+). Agalsidase alfa is a recombinant human α-galactosidase A similar to [agalsidase beta]. While patients generally do not experience a clinically significant difference in outcomes between the two drugs, some patients may experience greater benefit with agalsidase beta. Use of agalsidase beta has decreased in Europe, in favor of agalsidase alfa, after a contamination event in 2009. Agalsidase alfa was granted EMA approval on 3 August 2001. See also: Eliglustat (has active moiety); Agalsidase Beta (annotation moved to). Drug Indication Agalsidase alfa is indicated in the treatment of Fabry disease. Replagal is indicated for long-term enzyme-replacement therapy in patients with a confirmed diagnosis of Fabry disease (α-galactosidase-A deficiency). Mechanism of Action α-galactosidase A is uptaken by cells via the mannose 6 phosphate receptor. Agalsidase alfa hydrolyzes globotriaosylceramide and other glycosphingolipids that would normally be hydrolyzed by endogenous α-galactosidase A. Preventing the accumulation of glycosphingolipids prevents or reduces the severity of manifestations of Fabry disease such as renal failure, cardiomyopathy, or cerebrovascular events. Pharmacodynamics Agalsidase alfa is a recombinant human α-galactosidase A used as enzyme replacement therapy in the treatment of Fabry disease. It has a long duration of action and a wide therapeutic index. Patients should be counselled regarding the risk of infusion related reactions and hypersensitivity. |
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.) |