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PZ-2891

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Chemical Structure| 2170608-82-7 同义名 : -
CAS号 : 2170608-82-7
货号 : A1142882
分子式 : C20H23N5O
纯度 : 99%+
分子量 : 349.43
MDL号 : MFCD31812779
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 80 mg/mL(228.94 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 PANK (Pantothenate kinase) is a metabolic enzyme that regulates cellular coenzyme A (CoA) levels, inactivating of which could lead to pantothenate kinase associated neurodegeneration. PZ-2891 is a brain-permeable allosteric PANK activator with IC50 value of 1.3nM for PANK3. PZ-2891 stabilized PANK3 by ∼7 °C in a cellular thermal shift (CETSA) assay and increased total intracellular CoA levels at concentration of 10μM in a human liver-derived cell line post 24h. Oral administration of PZ-2891 at dose of 15mg/kg and 20mg/kg every 12 h for 5 doses activated CoA synthesis in liver, forebrain and hindbrain of mice dosed with 100mg/kg pantothenate. Therapy with PZ-2891 rescued the weight loss, severe locomotor impairment and early death of a knockout mouse model of brain CoA deficiency.
作用机制 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.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.86mL

0.57mL

0.29mL

14.31mL

2.86mL

1.43mL

28.62mL

5.72mL

2.86mL
参考文献

[1]Sharma LK, Subramanian C, et al. A therapeutic approach to pantothenate kinase associated neurodegeneration. Nat Commun. 2018 Oct 23;9(1):4399.