| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Iron chelator
SP-420 is an iron chelator that targets and binds to free iron in the body. By chelating iron, it induces the excretion of iron (via bile and urine), prevents iron accumulation, and prevents cellular and/or tissue damage associated with iron overload. Its mechanism involves the formation of a stable complex with ferric iron, which is then excreted. |
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| ln Vitro |
Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to determine if a comparable reduction in renal toxicity could be achieved by performing the same structural manipulations on 1 itself[1].
In vitro, SP-420 is an iron chelator with a higher iron-clearing efficiency than desferrithiocin. Its ability to bind iron can be assessed in cell-free assays (e.g., spectrophotometric measurement of iron complex formation) or in cell culture models of iron overload, where it reduces intracellular iron levels. |
| ln Vivo |
The iron-clearing efficiency and ferrokinetics were evaluated in rats and primates; toxicity assessments were carried out in rodents. The resulting DFT ligands demonstrated a reduction in toxicity that was equivalent to that of the DADFT analogues and presented with excellent iron-clearing properties[1].
In vivo, SP-420 induces iron excretion in rat bile and urine with an iron-clearing efficiency (ICE) value of 26.7% when administered at a dose of 300 μmol/kg. It decreases iron levels in rat liver and heart at 384 μmol/kg per day. It is used for the treatment of iron overload diseases such as thalassemia and hemochromatosis. |
| Enzyme Assay |
The stoichiometries of the ligand-Fe(III) complexes of 6, 8 and 10 were determined spectrophotometrically using Job’s plots. Solutions were monitored at the visible λmax of the Fe(III) complexes (498 nm for 6, 484 nm for 8, and 485 nm for 10). A 100 mM Tris HCl buffer was used to maintain the pH at 7.4. Solutions containing different ligand/Fe(III) ratios were prepared by mixing appropriate volumes of 1.0 mM ligand solution and 1.0 mM Fe(III)-nitriloacetate (NTA) in Tris-HCl buffer. The 1.0 mM Fe(III)-NTA solution was prepared immediately prior to use by dilution of a 41.6 mM Fe(III)-NTA stock solution with the Tris HCl buffer, whereas the ligand’s stock solution was prepared by dissolving the ligand as its monosodium salt in Tris HCl buffer at pH 7.4. The Fe(III)-NTA stock solution was prepared by mixing equal volumes of 90 mM of FeCl3 and 180 mM trisodium NTA. The iron content of the Fe(III)-NTA solution was verified by AAS[1].
In vitro binding assays for SP-420 typically measure its affinity for iron. The compound's ability to chelate iron can be assessed using colorimetric or fluorometric assays that measure the displacement of iron from a reporter molecule (e.g., ferrozine) or the formation of a colored complex. |
| Cell Assay |
In vitro cellular assays for SP-420 involve treating cells (e.g., hepatocytes, cardiomyocytes) with the compound and measuring its effects on intracellular iron levels (using fluorescent probes like calcein-AM) and cellular viability. These assays are used to assess its efficacy in reducing iron overload in a cellular context.
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| Animal Protocol |
Cannulation of Bile Duct in Non-iron-overloaded Rats[1]
The cannulation has been described previously. Bile samples were collected from male Sprague-Dawley rats (400–450 g) at 3 h intervals for up to 48 h. The urine sample(s) was taken at 24 h intervals. Sample collection and handling are as previously described.[1] Iron Loading of C. apella Monkeys[1] The monkeys were iron overloaded with intravenous iron dextran as specified in earlier publications to provide about 500 mg of iron per kg of body weight; the serum transferrin iron saturation rose to between 70 and 80%. At least 20 half-lives, 60 days, elapsed before any of the animals were used in experiments evaluating iron-chelating agents. In vivo animal models for SP-420 include rat models of iron overload (e.g., iron-dextran administered). The compound is administered orally, and its effects on iron excretion in bile and urine, as well as iron levels in tissues such as the liver and heart, are assessed. Pharmacokinetic parameters are also evaluated. |
| ADME/Pharmacokinetics |
SP-420 has a molecular formula of C16H21NO6S and a molecular weight of 355.41 g/mol. Its chemical name is (4S)-4,5-Dihydro-2-(2-hydroxy-4-(2-(2-methoxyethoxy)ethoxy)phenyl)-4-methyl-4-thiazolecarboxylic acid. It is an orally active iron chelator and is typically stored as a powder at -20°C, soluble in DMSO.
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| Toxicity/Toxicokinetics |
SP-420 is an iron chelator with a well-characterized mechanism of action. As with any metal chelator, potential toxicity may include the depletion of essential metals (e.g., zinc, copper) and effects on mineral metabolism. It is for research use only and is not approved for human therapeutic use.
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| References |
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| Additional Infomation |
SP-420 is currently undergoing clinical trials (NCT03801889) for patients with transfusion-dependent β-thalassemia or other rare anemias. SP-420 is an orally bioavailable iron chelator, a derivative of deferasiocin, with iron chelating and protective effects, and can be used to treat iron overload disorders. After oral administration, SP-420 targets and chelates free iron. This promotes iron excretion, prevents iron accumulation, and protects against cell and/or tissue damage associated with iron overload.
SP-420 is a novel, orally active iron chelator and a derivative of desferrithiocin. It has an iron-clearing efficiency (ICE) value of 26.7 and is used for the treatment of iron overload diseases. The compound is for research use only and is not approved for human therapeutic use. |
| Molecular Formula |
C16H21NO6S
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|---|---|
| Molecular Weight |
355.406043767929
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| Exact Mass |
355.108
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| Elemental Analysis |
C, 54.07; H, 5.96; N, 3.94; O, 27.01; S, 9.02
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| CAS # |
911714-45-9
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| Related CAS # |
911714459; 911714 45 9; 911714-45-9;
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| PubChem CID |
135511704
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| Appearance |
Typically exists as Light yellow to khaki solids at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
562.2±60.0 °C at 760 mmHg
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| Flash Point |
293.8±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.580
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| LogP |
-0.07
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
24
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| Complexity |
460
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| Defined Atom Stereocenter Count |
1
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| SMILES |
OC1C=C(OCCOCCOC)C=CC=1C1SC[C@](C)(C(=O)O)N=1
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| InChi Key |
YASYAEVZKXPYIZ-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C16H21NO6S/c1-16(15(19)20)10-24-14(17-16)12-4-3-11(9-13(12)18)23-8-7-22-6-5-21-2/h3-4,9,18H,5-8,10H2,1-2H3,(H,19,20)/t16-/m1/s1
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| Chemical Name |
(4S)-4,5-Dihydro-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-4-thiazolecarboxylic acid
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| Synonyms |
SP-420; SP420; UNII-WBX54NZ436; WBX54NZ436; (4S)-2-[2-hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl]-4-methyl-5H-1,3-thiazole-4-carboxylic acid; (4S)-2-{2-Hydroxy-4-[2-(2-methoxyethoxy)ethoxy]phenyl}-4-methyl-4,5-dihydro-1,3-thiazole-4-carboxylic acid; (4S)-4,5-Dihydro-2-(2-hydroxy-4-(2-(2-methoxyethoxy)ethoxy)phenyl)-4-methyl-4-thiazolecarboxylic acid; (S)-2-(2-hydroxy-4-(2-(2-methoxyethoxy)ethoxy)phenyl)-4-methyl-4,5-dihydrothiazole-4-carboxylic acid;SP 420
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ≥ 38 mg/mL (~106.92 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8137 mL | 14.0683 mL | 28.1365 mL | |
| 5 mM | 0.5627 mL | 2.8137 mL | 5.6273 mL | |
| 10 mM | 0.2814 mL | 1.4068 mL | 2.8137 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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