GNE-3511

GNE-3511 is a selective and highly potent inhibitor of dual leucine zipper kinase (DLK), also known as MAP3K12 (Ki = 500 pM). It also inhibits phosphorylated JNK (IC50 = 30 nM) and is highly selective for DLK over other MAP kinases (IC50 > 5,000 nM for MKK4 and MKK7), JNKs (IC50s = 129, 514, and 364 nM for JNK1, JNK2, and JNK3, respectively), and mixed-lineage kinases (MLKs, IC50s = 68, 767, and 602 nM for MLK1, MLK2, and MLK3, respectively). GNE-3511 protects primary neurons in an in vitro axon degeneration assay (IC50 = 107 nM). In an MPTP mouse model of Parkinson's disease, a high dose of GNE-3511 (75 mg/kg) completely suppresses phosphorylated c-Jun (p-c-Jun) expression, while a low dose (37.5 mg/kg) moderately reduces its expression.Formal Name: 2-[[6-(3,3-difluoro-1-pyrrolidinyl)-4-[1-(3-oxetanyl)-4-piperidinyl]-2-pyridinyl]amino]-4-pyridinecarbonitrile. CAS Number: 1496581-76-0. Molecular Formula: C23H26F2N6O. Formula Weight: 440.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: 20 mg/ml, Methanol: 1 mg/ml. lambdamax: 275, 320, 358 nm. SMILES: FC(C1)(F)CCN1C2=CC(C3CCN(C4COC4)CC3)=CC(NC5=CC(C#N)=CC=N5)=N2. InChi Code: InChI=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). InChi Key: RHFIAUKMKYHHFA-UHFFFAOYSA-N.