Atpenin A5

Names

[ CAS No. ]:
119509-24-9

[ Name ]:
Atpenin A5

[Synonym ]:
3-[(2S,4S,5R)-5,6-Dichloro-2,4-dimethylhexanoyl]-2-hydroxy-5,6-dimethoxy-4(1H)-pyridinone
AT5
3-[(2S,4S,5R)-5,6-DICHLORO-2,4-DIMETHYL-1-OXOHEXYL]-4-HYDROXY-5,6-DIMETHOXY-2(1H)-PYRIDINONE
Atpenin A5
4(1H)-Pyridinone, 3-[(2S,4S,5R)-5,6-dichloro-2,4-dimethyl-1-oxohexyl]-2-hydroxy-5,6-dimethoxy-

Biological Activity

[Description]:

Atpenin A5 is a potent and highly specific complex II inhibitor (IC50 ~10 nM), and is an effective mKATP channel agonist and cardioprotective agent[1].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

[In Vitro]

Atpenin A5 shows the inhibition profile for submitochondrial particles (SMPs), mitochondria, and cardiomyocytes, with IC50 values of 8.3, 9.3, and 8.5 nM, respectively. Atpenin A5 (AA5) is a potent and specific complex II inhibitor. Atpenin A5 (1 nM) also activates the mKATP channel and protects against simulated ischemia-reperfusion (IR) injury in isolated cardiomyocytes[1].

[In Vivo]

Atpenin A5 is a potent inhibitor of succinate dehydrogenase (SDH). Succinate dehydrogenase inhibition by Atpenin A5 promotes cardiomyocyte mitosis and regeneration in the postnatal heart after myocardial infarction (MI). Atpenin A5-injected mice demonstrated myocardial thickness at the infarct zone and a significant reduction in scar size compared with controls[2]. Animal Model: Neonatal mice[2] Dosage: 100 μg/kg Administration: Injected daily Result: Demonstrated myocardial thickness at the infarct zone and a significant reduction in scar size compared with controls.

[References]

[1]. Andrew P Wojtovich, et al. The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial KATP channels. Basic Res Cardiol. 2009 Mar;104(2):121-9.

[2]. Jiyoung Bae, et al. Malonate Promotes Adult Cardiomyocyte Proliferation and Heart Regeneration. Circulation. 2021 May 18;143(20):1973-1986.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
532.6±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₅H₂₁Cl₂NO₅

[ Molecular Weight ]:
366.237

[ Flash Point ]:
275.9±30.1 °C

[ Exact Mass ]:
365.079681

[ PSA ]:
88.62000

[ LogP ]:
-0.80

[ Vapour Pressure ]:
0.0±3.2 mmHg at 25°C

[ Index of Refraction ]:
1.534

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CJ8800000

CHEMICAL NAME :: Atpenin A5

CAS REGISTRY NUMBER :: 119509-24-9

LAST UPDATED :: 199203

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C15-H21-Cl2-N-O5

MOLECULAR WEIGHT :: 366.27

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 41,1769,1988