GNE-3511

小分子

GNE-3511

G647232-50mg

50mg

≥99%

-20°C储存

超低温冰袋运输

GNE-3511 is an orally active bioavailable and brain-penetrant dual leucine zipper kinase (DLK) inhibitor with a K i of 0.5 nM. GNE-3511 can cross the blood-brain-barrier and can be used for the research of neurodegenerative diseases In Vitro GNE-3511 has inhibitory activity for p-JNK and DRG with IC 50 values of 30 nM and 107 nM, respectively. GNE-3511 has kinase selectivity for MKK4, MKK7, JNK1, JNK2, JNK3, MLK1, MLK2 and MLK3 with IC 50 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo 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. Pharmacokinetic Parameters of GNE-3511 (iv.; 1 mg/kg or po.; 5 mg/kg). species CL p (mL/min/kg Vd ss (L/kg t 1/2 (h) F (%) B u /P u CSF/P u mouse 56 2.5 0.6 45 0.24 at 6 h rat 30 3.7 1.8 63 0.7 0.4 dog 41 6.5 4 32 0.4 cynomolgous 16 3.1 2.4 19 0.6 MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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 dogDosage: 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. Form:Solid IC50& Target: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)

GNE-3511 是一种具有口服活性的生物可利用性和脑穿透性双重亮氨酸拉链激酶 (DLK) 抑制剂，其 K i 为 0.5 nM。GNE-3511 可穿过血脑屏障，可用于神经退行性疾病的研究。

1496581-76-0

C23H26F2N6O

440.49 g/mol

72547959

C1CN(CCC1C2=CC(=NC(=C2)N3CCC(C3)(F)F)NC4=NC=CC(=C4)C#N)C5COC5

2-[[6-(3,3-difluoropyrrolidin-1-yl)-4-[1-(oxetan-3-yl)piperidin-4-yl]pyridin-2-yl]amino]pyridine-4-carbonitrile

1S/C23H26F2N6O/c24-23(25)4-8-31(15-23)22-11-18(17-2-6-30(7-3-17)19-13-32-14-19)10-21(29-22)28-20-9-16(12-26)1-5-27-20/h1,5,9-11,17,19H,2-4,6-8,13-15H2,(H,27,28,29)

RHFIAUKMKYHHFA-UHFFFAOYSA-N

C1CN(CCC1C2=CC(=NC(=C2)N3CCC(C3)(F)F)NC4=NC=CC(=C4)C#N)C5COC5

72547959

DMSO : 31.25 mg/mL (70.94 mM; Need ultrasonic)

1

9

5

440.214 Da

440.214 Da

77.300 Ų

32

0

689.000

0

1

3.200