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Purity: ≥98%
PZ-2891 (PZ2891) is an orally bioavailable, and brain penetrant allosteric activator of Pantothenate kinase (PANK) with neuroprotective activity. It acts as both an orthosteric inhibitor with IC50 of 1.3 nM and an allosteric activator of PANK3 in the presence of acetyl-CoA in biochemical assays. Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular coenzyme A (CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 lead to pantothenate kinase associated neurodegeneration (PKAN). PZ-2891 occupies the pantothenate pocket and engages the dimer interface to form a PANK•ATP•Mg2+•PZ-2891 complex. The binding of PZ-2891 to one protomer locks the opposite protomer in a catalytically active conformation that is refractory to acetyl-CoA inhibition. Oral administration of PZ-2891 increases CoA levels in mouse liver and brain. A knockout mouse model of brain CoA deficiency exhibited weight loss, severe locomotor impairment and early death. Knockout mice on PZ-2891 therapy gain weight, and have improved locomotor activity and life span establishing pantazines as novel therapeutics for the treatment of PKAN.
| ln Vitro |
PZ-2891 inhibits the mouse pantothenate kinases PANK1β, PANK2, and PANK3 withIC50 values of 48.7±5.1 nM, 1.0±0.1 nM, and 1.9±0.2 nM, respectively[1].
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| References |
[1]. Sharma LK, et al. A therapeutic approach to pantothenate kinase associated neurodegeneration. Nat Commun. 2018 Oct 23;9(1):4399.
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| Molecular Formula |
C20H23N5O
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| Molecular Weight |
349.44
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| CAS # |
2170608-82-7
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| SMILES |
N#CC1=NN=C(N2CCN(C(CC3=CC=C(C(C)C)C=C3)=O)CC2)C=C1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8617 mL | 14.3086 mL | 28.6172 mL | |
| 5 mM | 0.5723 mL | 2.8617 mL | 5.7234 mL | |
| 10 mM | 0.2862 mL | 1.4309 mL | 2.8617 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.
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.
Chemical progression of pantazines.
Activation of PanK by PZ-2891.Nat Commun.2018Oct 23;9(1):4399. |
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Pantazine modulation of intracellular CoA levels.Nat Commun.2018Oct 23;9(1):4399. |
Pantothenate concentration and PZ-2891 activation of CoA synthesis in animals.Nat Commun.2018Oct 23;9(1):4399. |
PZ-2891 binds to the PANK3•ATP•Mg2+complex with nM affinity.Nat Commun.2018Oct 23;9(1):4399. |
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Activation of CoA synthesis in liver, forebrain and hindbrain of male and female animals treated with PZ-2891.Nat Commun.2018Oct 23;9(1):4399. |
 PZ-2891 therapy inSynCre+PANK1,PANK2neuronal knockout mice.Nat Commun.2018Oct 23;9(1):4399. |
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