PZ-3022
PZ-3022 is an orally active allosteric agonist of pantothenate kinase (PanK) with an EC50 of 5.3 nM against PanK3. PZ-3022 antagonizes the inhibitory effect of C3-CoA. PZ-3022 increases CoA levels in cells and the liver, upregulates CoASH and C2-CoA, downregulates C3-CoA, and restores impaired TCA cycle and mitochondrial function. PZ-3022 can be used for the research of propionic acidemia and metabolic CoA deficiency.
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- CAS No.: 2170608-85-0
- Formule: C20H21N5O
- Masse moléculaire:347.41
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
PZ-3022 potently activates purified human PanK3 with an EC50 of 5.3 nM via allosteric binding to the PanK dimer[1].
PZ-3022 effectively elevates total intracellular CoA in cultured human C3A hepatoma cells and protects all PanK isoforms from C3-CoA-mediated inhibition[1].
PZ-3022 (compound 1) potently inhibits purified PANK3 enzyme with a Ki value of 5.3 nM; it also inhibits purified PANK1β enzyme with a Ki value of 789 nM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Pcca-/-PCCA(A138T)tg/0 (male and female, weaned at 21 days, analyzed at 70 days of age, propionic acidemia model)[1]
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Dosage:10 mg/kg (short-term); 30 mg/kg (short-term); 75 ppm (long-term)
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Administration:p.o.; 3 doses at 24-hour intervals (short-term); chow; daily; from weaning to 70 days of age (long-term)
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Result:Raises hepatic CoASH, C2-CoA and total CoA, lowers hepatic C3-CoA, and optimizes hepatic C3:C2-CoA ratio in PA mice (short-term 10 or 30 mg/kg).
Decreases plasma C3:C2-carnitine ratio in male PA mice (short-term 30 mg/kg).
Returns hepatic CoASH and C2-CoA to baseline levels, reduces hepatic C3-CoA and hepatic C3:C2-CoA ratio in PA mice (long-term 75 ppm).
Modulates liver and plasma carnitine levels and cuts plasma C3:C2-carnitine ratio in PA mice of both sexes (long-term 75 ppm).
Lowers urinary TCA cycle metabolites with an 80% drop in malate and normalizes heart:body weight ratio in PA mice (long-term 75 ppm).
Chemical Information
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CAS No. 2170608-85-0
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Masse moléculaire 347.41
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Formule C20H21N5O
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SMILES
N#CC1=NN=C(N2CCN(CC2)C(CC3=CC=C(C4CC4)C=C3)=O)C=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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Mitochondrial membrane-potential fluorescent assay
Mitochondrial membrane potential fluorescent assays estimate ΔΨm in living cells using lipophilic cationic dyes such as TMRM, TMRE, rhodamine 123, and JC-1, which accumulate in mitochondria according to membrane polarization; loss of signal after FCCP or CCCP treatment is interpreted as mitochondrial depolarization. TMRM/TMRE and rhodamine 123 are commonly used for semi-quantitative live-cell microscopy or flow cytometry, while JC-1 can report a shift from red aggregate fluorescence to green monomer fluorescence during depolarization; interpretation requires controls because dye concentration, quenching mode, cell type, dye efflux, and mitochondrial mass can affect fluorescence independently of ΔΨm.
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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PZ-3022 Related Classifications
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