GNE-3511

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GNE-3511 是一种有效、选择性、口服生物利用度、脑渗透性双亮氨酸拉链激酶 (DLK、MAP3K12) 抑制剂，Ki 小于 0.5 nM。

GNE-3511 is a potent, selective, orally bioavailable, brain-penetrant dual leucine zipper kinase (DLK, MAP3K12) inhibitor with Ki of <0.5 nM, displays >100-fold selectivity over MKK4/7, JNK1/2/3, MLK1/2/3; inhibits p-JNK with IC50 of 30 nM, displays concentration-dependent protection of neurons from degeneration in vitro (DRG IC50=107 nM) and demonstrates dose-dependent activity in multiple animal models of neurodegenerative disease.

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.

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 plasmaclearances, moderate volumes of distribution, short half-lives,and brain penetration.Animal Model:Cystitis mouse modelDosage: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.

GNE3511 | GNE 3511

MAPK/ERK Signaling

MEK

DLK|MAP3K12

Cancer

——

1496581-76-0

440.489

C23H26F2N6O

>98% (HPLC)

DMSO: ≥ 32 mg/mL

N#CC1=CC(NC2=NC(N3CC(F)(F)CC3)=CC(C4CCN(C5COC5)CC4)=C2)=NC=C1

4-Pyridinecarbonitrile, 2-[[6-(3,3-difluoro-1-pyrrolidinyl)-4-[1-(3-oxetanyl)-4-piperidinyl]-2-pyridinyl]amino]-

(-20℃)

With Ice Pack

≥ 2 years