A selective and highly potent inhibitor of DLK
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GNE-3511

Item No. 19174

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
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(Learn about Variance in Solubility)
DMSO: 20 mg/mlMethanol: 1 mg/ml
λmax
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
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    1 mg

    $48

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    5 mg

    $160

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    10 mg

    $230

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    25 mg

    $514

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    Product Description

    GNE-3511 is a selective and highly potent inhibitor of dual leucine zipper kinase (DLK), also known as MAP3K12 (Ki = 500 pM).1 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.

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Patel, S., Cohen, F., Dean, B.J., et al. Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models. J. Med. Chem. 58(1), 401-418 (2015).