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Ferric maltol

Alias: Ferric maltol; Iron (III) maltol; ST10; ST 10021; WHO 9974ST-10; ST 10-021ST-10021; WHO-9974ST; 10 ST10-021; ST-10-021; ST10021; WHO9974; Ferric maltol; 33725-54-1; Iron (III) maltol; st10; iron maltol; MA10QYF1Z0; Ferric maltol [INN]; Ferric maltol [USAN];
Cat No.:V37991 Purity: =100%
Ferric maltol (ST10;ST 10021; WHO 9974;ST-10;ST 10-021; tradenames Accrufer and Feraccru) is an orally bioavailavleiron containing medication for the treatment of adults with low iron stores.
Ferric maltol
Ferric maltol Chemical Structure CAS No.: 33725-54-1
Product category: New8
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
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100mg
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Purity & Quality Control Documentation

Purity: =100%

Product Description

Ferric maltol (ST10; ST 10021; WHO 9974; ST-10; ST 10-021; trade names Accrufer and Feraccru) is an orally bioavailavle iron containing medication for the treatment of adults with low iron stores. It is used to provide supplemental iron to patients with an iron deficiency.

Biological Activity I Assay Protocols (From Reference)
Targets
Metabolic Disease
ln Vitro
Serum ferritin, blood hemoglobin, reticulocyte hemoglobin, serum iron, and serum ferritin levels are all increased when iron maltol is taken [1].
ln Vivo
According to research on animals, unabsorbed iron from iron maltol can at least stay in the small intestine in a chelated form, lowering the possibility of local toxicity and the risk of free iron damaging intestinal mucosa [1].
Animal Protocol
Introduction: Iron deficiency anemia affects up to three quarters of patients with inflammatory bowel disease (IBD). It can significantly impact the quality of life and the ability to work by impairing physical, emotional, and cognitive functioning. The etiology of iron deficiency anemia is multifactorial and oral or intravenous iron replacement is necessary. However, oral iron supplements are often discontinued prematurely due to poor tolerability or insufficient efficacy. Moreover, intravenous supplementation is inconvenient, associated with potentially serious safety risks, and a burden on healthcare resources.[1]

Areas covered: Ferric maltol is a novel ferric iron compound with potential use as an oral therapy for iron deficiency anemia. This overview explains how the molecule’s design impacts clinical outcomes and summarizes available clinical data (ranging from early comparisons with ferrous sulfate to randomized, placebo-controlled, Phase III data in patients with IBD known to be intolerant of oral ferrous products).[1]

Expert opinion: Ferric maltol offers the ability to treat iron deficiency anemia in mild-to-moderate IBD without resorting to intravenous therapy, even in those who are intolerant of oral ferrous products. This clinical benefit has the potential to change treatment pathways and increase choice, not only in IBD but also perhaps in many areas beyond gastroenterology.
ADME/Pharmacokinetics
Absorption, Distribution and Excretion
Maltol iron dissociates in the gastrointestinal tract, resulting in a time to peak iron concentration (Tmax) of 1.5–3.0 hours. Following a single dose, the mean serum iron concentration in iron-deficient patients increases by 14 ± 6 µmol/L. The bioavailability of a 60 mg dose is approximately 14%. Sixty minutes after injection of radiolabeled maltol iron, 11 ± 2% of the dose is present in the bone marrow, 18 ± 1% in the liver, and 2.6 ± 1% in the urine. The AUC of maltol is 0.022–0.205 hµg/mL, and the AUC of maltol glucuronide is 9.83–30.9 hµg/mL. After oral administration of maltol iron, 39.8–60% is excreted in the urine as a glucuronide conjugate. Iron and maltol iron are not excreted in the urine; unabsorbed maltol iron is excreted in the feces. Data regarding the volume of distribution of ferric maltol are unclear. Data regarding the clearance rate of ferric maltol are unclear. Metabolism/Metabolites In vitro studies have shown that the metabolism of ferric maltol mainly involves UGT1A6-mediated glucuronidation and sulfation of maltol. Biological Half-Life The half-life of maltol is 0.7 hours.
Toxicity/Toxicokinetics
Protein Binding
There is currently no publicly available data regarding the protein binding of maltol iron.
References
[1]. Stallmach A, et al. Ferric maltol (ST10): a novel oral iron supplement for the treatment of iron deficiency anemia in inflammatory bowel disease. Expert Opin Pharmacother. 2015;16(18):2859-67.
Additional Infomation
Ferric maltol is a complex of three maltol molecules bound to iron (III) atoms. It has higher bioavailability than ferrous iron and does not deposit in the duodenum as insoluble ferric hydroxide and ferric phosphate. Ferric maltol was described as a potential treatment for iron deficiency in the literature as early as the late 1980s. Ferric maltol was approved by the U.S. Food and Drug Administration (FDA) on July 25, 2019.
See also: Ferric cations (containing the active moiety).
Drug Indications

Feraccru is indicated for the treatment of iron deficiency in adults.
Feraccru is indicated for the treatment of iron deficiency in adults.
Treatment of Iron Deficiency

Mechanism of Action

When ferric maltol dissociates, the iron atoms are provided to an unknown iron absorption mechanism in the ileum and duodenum, possibly β3 integrin or divalent metallotransferrin 1. After entering the bloodstream, the iron binds to transferrin and ferritin.
Pharmacodynamics
Ferric maltol is used to supplement iron in patients with iron deficiency. It has a broad therapeutic index, and patients typically take 30 mg twice daily, while concentrations of 20 mg/kg may cause toxicity. Patients should be informed of the risks of inflammatory bowel disease flare-ups, iron overload, and accidental ingestion in children.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C₁₈H₁₅FEO₉
Molecular Weight
431.15
Exact Mass
431.006
Elemental Analysis
C, 50.14; H, 3.51; Fe, 12.95; O, 33.40
CAS #
33725-54-1
PubChem CID
169535
Appearance
Typically exists as Purple to purplish red solids at room temperature
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
9
Rotatable Bond Count
0
Heavy Atom Count
28
Complexity
200
Defined Atom Stereocenter Count
0
SMILES
Cl.CC1C=CC(C(C(N2CCCCC2)C)=O)=C(C)C=1
InChi Key
AHPWLYJHTFAWKI-UHFFFAOYSA-K
InChi Code
InChI=1S/3C6H6O3.Fe/c3*1-4-6(8)5(7)2-3-9-4;/h3*2-3,8H,1H3;/q;;;+3/p-3
Chemical Name
iron(3+);2-methyl-4-oxopyran-3-olate
Synonyms
Ferric maltol; Iron (III) maltol; ST10; ST 10021; WHO 9974ST-10; ST 10-021ST-10021; WHO-9974ST; 10 ST10-021; ST-10-021; ST10021; WHO9974; Ferric maltol; 33725-54-1; Iron (III) maltol; st10; iron maltol; MA10QYF1Z0; Ferric maltol [INN]; Ferric maltol [USAN];
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)
Solubility Data
Solubility (In Vitro)
DMSO : ~12.5 mg/mL (~28.99 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: 1.25 mg/mL (2.90 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.3194 mL 11.5969 mL 23.1938 mL
5 mM 0.4639 mL 2.3194 mL 4.6388 mL
10 mM 0.2319 mL 1.1597 mL 2.3194 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.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.

Clinical Trial Information
Perioperative Iron for Colorectal Cancer (PICoC Study)
CTID: NCT05177484
Phase: Phase 3
Status: Recruiting
Date: 2023-12-28
Evaluate the Safety and Efficacy of Ferric Maltol Oral Suspension vs. Ferrous Sulfate Oral Liquid in Children and Adolescents Aged 2 to 17 Years With Iron-deficiency Anaemia, With a Single Arm Study in Infants Aged 1 Month to Less Than 2 Years
CTID: NCT05126901
Phase: Phase 3
Status: Recruiting
Date: 2023-12-22
Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease
CTID: NCT05456932
Phase: Phase 4
Status: Recruiting
Date: 2023-03-31
ORal IrON Supplementation With Ferric Maltol in Treating Iron Deficiency and Anaemia in Patients With Heart Failure (ORION-HF)
CTID: NCT05697211
Phase: Phase 4
Status: Recruiting
Date: 2023-03-03
Evaluate the PK, Safety, Tolerability of Ferric Maltol at 3 Dosage Levels in Paediatric Subjects With Iron Deficiency
CTID: NCT03181451
Phase: Phase 1
Status: Completed
Date: 2021-10-06
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