Physicochemical Properties
| Molecular Formula | ZN+2 |
| Exact Mass | 63.928 |
| CAS # | 9025-42-7 |
| PubChem CID | 32051 |
| Appearance | Typically exists as solid at room temperature |
| Melting Point | 419.5 °C |
| LogP | 0 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 0 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 1 |
| Complexity | 0 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | [Zn+2] |
| InChi Key | PTFCDOFLOPIGGS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/Zn/q+2 |
| Chemical Name | zinc(2+) |
| 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 Following weekly intravenous infusion of 1 mg/kg of velmanase alfa, the mean Cmax of 8 µg/mL at steady-state was reached at 1.8 hours after the start of administration. There is no information. The steady-state volume of distribution is 0.27 L/kg, indicating distribution confined to plasma. It does not cross the blood-brain barrier. The mean clearance of velmanase alfa from plasma is 6.7 mL/h/kg: it is consistent with rapid cellular uptake of velmanase alfa via mannose receptors. Metabolism / Metabolites Velmanase alfa is expected to undergo nonspecific degradation into small peptides and subsequently amino acids, similar to other natural occurring proteins. Biological Half-Life At the end of intravenous infusion, velmanase alfa plasma concentrations fell in a biphasic fashion with a mean terminal elimination half-life of about 30 hours. |
| Toxicity/Toxicokinetics |
Protein Binding There is no information. |
| Additional Infomation |
Zinc(2+) is a divalent metal cation, a zinc cation and a monoatomic dication. It has a role as a human metabolite and a cofactor. Velmanase alfa is a recombinant human lysosomal alpha-mannosidase developed for enzyme replacement therapy to treat alpha-mannosidosis. Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder. Patients with alpha-mannosidosis have a genetic mutation that causes a deficiency in the lysosomal enzyme alpha-mannosidase, which is an enzyme responsible for breaking down complex sugars in the body. The resulting accumulation of sugars in the body leads to an array of clinical manifestations leading to progressive neuromuscular and skeletal deterioration, such as skeletal abnormalities, motor function impairment, intellectual disability, and respiratory dysfunction. As long-term enzyme replacement therapy, velmanase alfa supplements or restores the function of deficient alpha-mannosidase. Velmanase alfa has an amino acid sequence of the monomeric protein identical to the naturally occurring human alpha-mannosidase. It was granted marketing authorization by the European Commission in March 2018 under the market name Lamzede as the first human recombinant form of alpha-mannosidase for the treatment of alpha-mannosidosis. In February 2023, the FDA also approved velmanase alfa for the same indication. Velmanase alfa is currently not approved in Canada. Zinc cation is a Copper Absorption Inhibitor. The physiologic effect of zinc cation is by means of Decreased Copper Ion Absorption. ZINC ion has been reported in Homo sapiens and Flexibacter with data available. Zinc is a metabolite found in or produced by Saccharomyces cerevisiae. See also: Zinc Sulfate (active moiety of); Zinc Chloride (active moiety of); Zinc Oxide (active moiety of) ... View More ... Drug Indication Velmanase alfa is an enzyme replacement therapy for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis. Treatment of alpha-mannosidosis Mechanism of Action Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder: it is a multi-systemic disease, characterized by a wide range of clinical manifestations including skeletal abnormalities, motor function impairment, intellectual disability, hearing loss, respiratory dysfunction, recurrent infections, and immunodeficiency usually presenting in early childhood. Alpha-mannosidosis is caused by pathogenic sequence variants in the MAN2B1 gene, leading to the deficiency of the lysosomal enzyme, alpha-mannosidase. Alpha-mannosidase is a lysosomal enzyme involved in glycoprotein catabolism. Deficient alpha-mannosidase results in the accumulation of mannose-rich oligosaccharides, causing impaired cellular function and apoptosis in all tissues. Velmanase alfa is a recombinant form of human alpha-mannosidase. Upon administration, velmanase alfa supplements or replaces natural alpha-mannosidase to properly break down hybrid and complex high-mannose oligosaccharides in the lysosome, reducing the amount of accumulated mannose-rich oligosaccharides. Pharmacodynamics Velmanase alfa is an enzyme replacement therapy that aims to reduce oligosaccharide levels in patients with alpha-mannosidosis. In clinical trials, reduced serum oligosaccharide levels and improvements in biochemical and functional measures were seen at 18 months and for up to four years of treatment. Reversing the organ damage or showing improvements in alpha-mannosidosis becomes increasingly difficult as the accumulation of end-organ damage progresses over time. Velmanase alfa has no effects on irreversible complications of the disorder, such as skeletal deformities, dysostosis multiplex, neurological manifestations, and impaired cognitive function. |
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.) |