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Mitapivat

Product Name
Mitapivat
CAS No.
1260075-17-9
Chemical Name
Mitapivat
Synonyms
Mitapivat;ag348;AG-348;MITAPIVAT;PKM2 ACTIVATOR;CAS 1260075-17-9;N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide;CS-2722;PKR-IN-1;Mitapivate;PKM2 activator;cas 1260075-17-9
CBNumber
CB72736694
Molecular Formula
C24H26N4O3S
Formula Weight
450.55
MOL File
1260075-17-9.mol
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Mitapivat Property

Boiling point:
667.3±65.0 °C(Predicted)
Density 
1.369±0.06 g/cm3(Predicted)
storage temp. 
Store at -20°C
solubility 
DMSO : 50 mg/mL (110.98 mM)
pka
6.69±0.50(Predicted)
form 
Solid
color 
White to off-white
InChI
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
InChIKey
XAYGBKHKBBXDAK-UHFFFAOYSA-N
SMILES
N1C2C(=CC=CC=2S(NC2=CC=C(C(N3CCN(CC4CC4)CC3)=O)C=C2)(=O)=O)C=CC=1
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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N-Bromosuccinimide Price

ChemScene
Product number
CS-3895
Product name
Mitapivat
Purity
99.97%
Packaging
5mg
Price
$120
Updated
2021/12/16
Axon Medchem
Product number
Axon2149
Product name
Mitapivat
Purity
99%
Packaging
5mg
Price
$137.5
Updated
2021/12/16
ChemScene
Product number
CS-3895
Product name
Mitapivat
Purity
99.97%
Packaging
10mg
Price
$210
Updated
2021/12/16
ChemScene
Product number
CS-3895
Product name
Mitapivat
Purity
99.97%
Packaging
50mg
Price
$650
Updated
2021/12/16
Crysdot
Product number
CD31004063
Product name
PKR-IN-1
Purity
98+%
Packaging
50mg
Price
$692
Updated
2021/12/16
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Mitapivat Chemical Properties,Usage,Production

Description

Mitapivat (trade name Pyrukynd) is a first-in-class drug developed by Agios Pharmaceuticals, Inc. It is an oral activator of red blood cell pyruvate kinase. Mitapivat is approved in the European Union and the United States for the treatment of hemolytic anemia and pyruvate kinase deficiency (PKD), a rare genetic disease associated with chronic hemolytic anemia. Clinical management of PKD was previously limited to supportive care, including red blood cell transfusions and splenectomy, which have short-term and long-term risks.

Uses

Mitapivat (AG-348) is an orally active pyruvate kinase allosteric activator. Mitapivat increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes, shows the potential to restore the activity of PK (pyruvate kinase)-deficient glycolytic pathways. Mitapivat can be used in study of PK deficiency[1][2][3].

Synthesis

The second building block of Mitapivat, sulfonamide 9.7, was prepared in two steps. First, sulfonyl chloride 9.4 was reacted with aniline 9.5 to give ester 9.6 in 99% yield (Figure 2.4.2). Ester 9.6 was hydrolyzed under alkaline conditions to give carboxylic acid 9.7 in 91% yield. Efficient coupling on a kilogram scale was achieved by activation of carboxylic acid 9.7 using CDI followed by addition of piperazine 9.3. Finally, water was added to the reaction mixture to induce crystallization of the product, giving mitapitant in 90% isolated yield.

in vivo

Mitapivat (50 mg/kg; p.o.; twice daily for 21 days) improves anemia in a mouse model for β-thalassemia[2].

Animal Model:WT C57B6 and Hbbth3/+ mice (both are 2-month-old female mice; β-thalassemia model)[2].
Dosage:50 mg/kg
Administration:In animal feedings; single daily for 3 weeks.
Result:Increased the expression of pyruvate kinase isoforms in both red cells and erythroid precursors from Hbbth3/+ mice.
Elevated pyruvate kinase activity in cells from Hbbth3/+ mice, and markedly increased ROS level in erythrocytes.
Increased the expression of PKM2 in polychromatic and orthochromatic erythroblasts of Hbbth3/+ mice.
Animal Model:WT C57B6 and Hbbth3/+ mice (both are 2-month-old female mice; β-thalassemia model)[2].
Dosage:50 mg/kg
Administration:Oral gavage, twice daily for 21 days.
Result:Ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice and increased ATP, reduced ROS production, as well as reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance.

References

[1] Kung C, et al. 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
[2] Matte A, et al. 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
[3] Rab MAE, et al. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249. DOI:10.3324/haematol.2019.238865

Mitapivat Preparation Products And Raw materials

Raw materials

Preparation Products

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Mitapivat Suppliers

China 94 United States 8 Global 102
Wuhan Shanhai Zhihe Biotechnology Co., Ltd.
Tel
17771424646
Email
shoubull@126.com
Country
China
ProdList
957
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58
Wuxi Donghe Pharmaceutical Technology Co., Ltd.
Tel
63313187 15358055255
Fax
QQ：63313187
Email
63313187@qq.com
Country
China
ProdList
1984
Advantage
58
Baiyi chemical (lianyungang) co. LTD
Tel
18552648286
Fax
996140672
Email
dajingsheng@126.com
Country
China
ProdList
382
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58
Nantong Hanfang Biotechnology Co. , Ltd.
Tel
hanfangpharma@126.com; 18616537568
Email
hanfangpharma@126.com
Country
China
ProdList
29965
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58
Hangzhou Yinghui Industrial Co.,Ltd
Tel
15355417531
Email
2028755477@qq.com
Country
China
ProdList
152
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58
Wuhan HSN Pharmaresearch CO., LTD.
Tel
027-81525288 18086100502
Fax
027-86589137
Email
linwell@126.com
Country
China
ProdList
233
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50
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2922
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55
ZHIWE CHEMTECH CO LTD
Tel
021-20221225 13917446399
Fax
QQ:115820162
Email
zwchem@163.com
Country
China
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616
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61
Nanjing Chemlin Chemical Co., Ltd
Tel
025-83697070
Fax
+86-25-83453306
Email
info@chemlin.com.cn
Country
China
ProdList
16075
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64
Haoyuan Chemexpress Co., Ltd.
Tel
021-58950125
Fax
(86) 21-58955996
Email
info@chemexpress.com
Country
China
ProdList
7552
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61

1260075-17-9, MitapivatRelated Search:


  • cas 1260075-17-9
  • MITAPIVAT;PKM2 ACTIVATOR;CAS 1260075-17-9
  • PKM2 activator
  • CS-2722
  • PKR-IN-1
  • PKM2 activator 1020
  • N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide
  • N-(4-{[4-(Cyclopropylmethyl)-1-piperazinyl]carbonyl}phenyl)-8-quinolinesulfonamide
  • Mitapivat
  • ag348
  • AG-348
  • AG348;AG348;AG-348
  • 8-Quinolinesulfonamide, N-[4-[[4-(cyclopropylmethyl)-1-piperazinyl]carbonyl]phenyl]-
  • Mitapivat(PKR-IN-1)
  • erythropoiesis,Mitapivat,AG 348,Pyruvate Kinase,ATP,RBC,PKD,Inhibitor,PKM2,pyruvate kinase deficiency,AG348,inhibit,AG-348
  • Mitapivate
  • Mitapivat (PKM2 activator 1020
  • 1260075-17-9
  • 260075-17-9