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MedKoo Cat#: 329505 | Name: Mitapivat free base
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Mitapivat, also known as AG348, is a potent, selective allosteric activator of the enzyme pyruvate kinase (PK), specifically the red blood cell isoform PKR. By enhancing PKR activity, Mitapivat increases glycolytic flux, leading to improved ATP production and redox balance, which is particularly beneficial in conditions such as pyruvate kinase deficiency (PKD) and other hemolytic anemias.Mitapivat directly binds to PKR, increasing its enzymatic activity in purified enzyme systems and red blood cell lysates. It enhances the enzyme's affinity for PEP, boosting its catalytic efficiency. Treatment with Mitapivat in vitro leads to reductions in markers of oxidative stress in red blood cells.

Chemical Structure

Mitapivat free base
Mitapivat free base
CAS#1260075-17-9 (free base)

Theoretical Analysis

MedKoo Cat#: 329505

Name: Mitapivat free base

CAS#: 1260075-17-9 (free base)

Chemical Formula: C24H26N4O3S

Exact Mass: 450.1726

Molecular Weight: 450.56

Elemental Analysis: C, 63.98; H, 5.82; N, 12.44; O, 10.65; S, 7.12

Price and Availability

Size Price Availability Quantity
25mg USD 250.00 2 weeks
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 weeks
200mg USD 1,250.00 2 weeks
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Related CAS #
1260075-17-9 (free base) 2559738-69-9 (HCl) 2329710-91-8 (sulfate) 2559738-74-6 (tosylate) 2151847-10-6 (sulfate hydrate)
Synonym
AG348; AG-348; AG 348; PKR-IN-1; PKM2 activator 1020; PKM2 activator; Mitapivat.
IUPAC/Chemical Name
N-{4-[4-(cyclopropylmethyl)piperazine-1-carbonyl]phenyl}quinoline-8-sulfonamide
InChi Key
XAYGBKHKBBXDAK-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H26N4O3S/c29-24(28-15-13-27(14-16-28)17-18-6-7-18)20-8-10-21(11-9-20)26-32(30,31)22-5-1-3-19-4-2-12-25-23(19)22/h1-5,8-12,18,26H,6-7,13-17H2
SMILES Code
O=S(C1=C2N=CC=CC2=CC=C1)(NC3=CC=C(C(N4CCN(CC5CC5)CC4)=O)C=C3)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Mitapivat (AG-348) is an orally active pyruvate kinase allosteric activator.
In vitro activity:
AG-348 is a potent activator of PK-R, stimulating activity to ∼5-fold of DMSO control with a concentration that increases activity by 50% (AC50) of 29 ± 17 nM (n = 108; Figure 1C). Examination of key kinetic parameters reveals that AG-348 increases the catalytic efficiency (kcat/KM) of WT PK-R, primarily by increasing the affinity for the substrate PEP, as reflected in the change of KM for PEP following AG-348 treatment (Figure 1D; Table 1). AG-348 also is an activator of PKM2 and PKL (supplemental Figure 1). Reference: Blood. 2017 Sep 14;130(11):1347-1356. https://pubmed.ncbi.nlm.nih.gov/28760888/
In vivo activity:
Oral mitapivat administration ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice. Increased ATP, reduced reactive oxygen species production, and reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance suggested enhanced metabolism following mitapivat administration in β-thalassemia. Mitapivat reduced duodenal Dmt1 expression potentially by activating the pyruvate kinase M2-HIF2α axis, representing a mechanism additional to Hamp in controlling iron absorption and preventing β-thalassemia-related liver iron overload. Reference: J Clin Invest. 2021 May 17;131(10):e144206. https://pubmed.ncbi.nlm.nih.gov/33822774/
Solvent mg/mL mM comments
Solubility
DMSO 32.9 73.05
Ethanol 2.0 4.44
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 450.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Kung C, Hixon J, Kosinski PA, Cianchetta G, Histen G, Chen Y, Hill C, Gross S, Si Y, Johnson K, DeLaBarre B, Luo Z, Gu Z, Yao G, Tang H, Fang C, Xu Y, Lv X, Biller S, Su SM, Yang H, Popovici-Muller J, Salituro F, Silverman L, Dang L. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017 Sep 14;130(11):1347-1356. doi: 10.1182/blood-2016-11-753525. Epub 2017 Jul 31. PMID: 28760888; PMCID: PMC5609468. 2. Quezado ZMN, Kamimura S, Smith M, Wang X, Heaven MR, Jana S, Vogel S, Zerfas P, Combs CA, Almeida LEF, Li Q, Quezado M, Horkayne-Szakaly I, Kosinski PA, Yu S, Kapadnis U, Kung C, Dang L, Wakim P, Eaton WA, Alayash AI, Thein SL. Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model. Blood Cells Mol Dis. 2022 Jul;95:102660. doi: 10.1016/j.bcmd.2022.102660. Epub 2022 Mar 12. PMID: 35366607; PMCID: PMC9148618. 3. Matte A, Federti E, Kung C, Kosinski PA, Narayanaswamy R, Russo R, Federico G, Carlomagno F, Desbats MA, Salviati L, Leboeuf C, Valenti MT, Turrini F, Janin A, Yu S, Beneduce E, Ronseaux S, Iatcenko I, Dang L, Ganz T, Jung CL, Iolascon A, Brugnara C, De Franceschi L. The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model. J Clin Invest. 2021 May 17;131(10):e144206. doi: 10.1172/JCI144206. PMID: 33822774; PMCID: PMC8121526.
In vitro protocol:
1. Kung C, Hixon J, Kosinski PA, Cianchetta G, Histen G, Chen Y, Hill C, Gross S, Si Y, Johnson K, DeLaBarre B, Luo Z, Gu Z, Yao G, Tang H, Fang C, Xu Y, Lv X, Biller S, Su SM, Yang H, Popovici-Muller J, Salituro F, Silverman L, Dang L. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017 Sep 14;130(11):1347-1356. doi: 10.1182/blood-2016-11-753525. Epub 2017 Jul 31. PMID: 28760888; PMCID: PMC5609468.
In vivo protocol:
1. Quezado ZMN, Kamimura S, Smith M, Wang X, Heaven MR, Jana S, Vogel S, Zerfas P, Combs CA, Almeida LEF, Li Q, Quezado M, Horkayne-Szakaly I, Kosinski PA, Yu S, Kapadnis U, Kung C, Dang L, Wakim P, Eaton WA, Alayash AI, Thein SL. Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model. Blood Cells Mol Dis. 2022 Jul;95:102660. doi: 10.1016/j.bcmd.2022.102660. Epub 2022 Mar 12. PMID: 35366607; PMCID: PMC9148618. 2. Matte A, Federti E, Kung C, Kosinski PA, Narayanaswamy R, Russo R, Federico G, Carlomagno F, Desbats MA, Salviati L, Leboeuf C, Valenti MT, Turrini F, Janin A, Yu S, Beneduce E, Ronseaux S, Iatcenko I, Dang L, Ganz T, Jung CL, Iolascon A, Brugnara C, De Franceschi L. The pyruvate kinase activator mitapivat reduces hemolysis and improves anemia in a β-thalassemia mouse model. J Clin Invest. 2021 May 17;131(10):e144206. doi: 10.1172/JCI144206. PMID: 33822774; PMCID: PMC8121526.
1: Yang H, Merica E, Chen Y, Cohen M, Goldwater R, Kosinski PA, Kung C, Yuan ZJ, Silverman L, Goldwasser M, Silver BA, Agresta S, Barbier AJ. Phase 1 Single- and Multiple-Ascending-Dose Randomized Studies of the Safety, Pharmacokinetics, and Pharmacodynamics of AG-348, a First-in-Class Allosteric Activator of Pyruvate Kinase R, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2019 Feb;8(2):246-259. doi: 10.1002/cpdd.604. Epub 2018 Aug 9. PubMed PMID: 30091852. 2: Kung C, Hixon J, Kosinski PA, Cianchetta G, Histen G, Chen Y, Hill C, Gross S, Si Y, Johnson K, DeLaBarre B, Luo Z, Gu Z, Yao G, Tang H, Fang C, Xu Y, Lv X, Biller S, Su SM, Yang H, Popovici-Muller J, Salituro F, Silverman L, Dang L. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017 Sep 14;130(11):1347-1356. doi: 10.1182/blood-2016-11-753525. Epub 2017 Jul 31. PubMed PMID: 28760888; PubMed Central PMCID: PMC5609468. 3: Christensen RD, Yaish HM, Nussenzveig RH, Agarwal AM. Siblings with severe pyruvate kinase deficiency and a complex genotype. Am J Med Genet A. 2016 Sep;170(9):2449-52. doi: 10.1002/ajmg.a.37828. Epub 2016 Jun 29. PubMed PMID: 27354418. 4: Croasdell G. European Hematology Association - 20th Annual Congress (June 11-14, 2015 - Vienna, Austria). Drugs Today (Barc). 2015 Jul;51(7):441-5. doi: 10.1358/dot.2015.51.7.2375757. PubMed PMID: 26261846.