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• 产品描述： GNE-3511 is an orally active bioavailable and brain-penetrant dual leucine zipper kinase (DLK) inhibitor with a Ki of 0.5 nM. GNE-3511 can cross the blood-brain-barrier and can be used for the research of neurodegenerative diseases

• 靶点： Ki: 0.5 nM (DLK); IC50: 30 nM (p-JNK), 107 nM (DRG); ＞5000 nM (MKK4), ＞5000 nM (MKK7), 129 nM (JNK1),514 nM (JNK2), 364 nM (JNK3), 67.8 nM (MLK1), 767 nM (MLK2) and 602 nM (MLK3);DNAAlkylation; MAPK

• 体外研究：
  GNE-3511 has inhibitory activity for p-JNK and DRG with IC50 values of 30 nM and 107 nM, respectively. GNE-3511 has kinase selectivity for MKK4, MKK7, JNK1, JNK2, JNK3, MLK1, MLK2 and MLK3 with IC50 values of ＞5000 nM, ＞5000 nM, 129 nM, 514 nM, 364 nM, 67.8 nM, 767 nM and 602 nM, respectively. GNE-3511 displays concentration-dependent protection of neurons from degeneration in vitro

• 体内研究：
  GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced nociceptive behavior by inhibiting DLK in mice. GNE-3511 (oral gavage; 75 mg/kg; single) suppresses CYP-induced edema and hemorrhage in mouse bladder. GNE-3511 (iv.; 1 mg/kg or po.; 5 mg/kg) exhibits moderate in vivo plasma clearances, moderate volumes of distribution, short half-lives, and brain penetration Animal Model: Cystitis mouse model Dosage: 75 mg/kg Administration: oral gavage;75 mg/kg; single Result: Significantly reduced the number of nociceptive behavior as well as nociceptive score.Had no impact on bladder weight, did not induce bladder edema or hemorrhage and significantly suppressed CYP-induced increase in bladder weight, bladder edema, and hemorrhage. Animal Model: mouse, rat, cynomolgus and dog Dosage: 1 mg/k, 5 mg/kg Administration: iv.; 1 mg/kg or po.; 5 mg/kg Result: Exhibited moderate in vivo plasma clearances, moderate volumes of distribution, short half-lives and brain penetration.

• 参考文献：
  1. Patel S et al. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J Med Chem. 2015 Jan 8;58(1):401-18. 2. Chen Jiang, et al. Neuronal Dual Leucine Zipper Kinase Mediates Inflammatory and Nociceptive Responses in Cyclophosphamide-Induced Cystitis. J Innate Immun. 2021;13(5):259-268.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.27 ml	11.351 ml	22.702 ml
  5 mM	0.454 ml	2.27 ml	4.54 ml
  10 mM	0.227 ml	1.135 ml	2.27 ml
  50 mM	0.045 ml	0.227 ml	0.454 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *