1. Immunology/Inflammation
  2. Salt-inducible Kinase (SIK)

HG-9-91-01 (Synonyms: SIK inhibitor 1)

Cat. No.: HY-15776 Purity: >98.0%
Handling Instructions

HG-9-91-01 is a potent and highly selective salt-inducible kinase (SIKs) inhibitor with IC50s of 0.92 nM, 6.6 nM and 9.6 nM for SIK1, SIK2 and SIK3 respectively.

For research use only. We do not sell to patients.
HG-9-91-01 Chemical Structure

HG-9-91-01 Chemical Structure

CAS No. : 1456858-58-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 357 In-stock
5 mg USD 286 In-stock
10 mg USD 433 In-stock
50 mg USD 1026 In-stock
100 mg USD 1596 In-stock
200 mg   Get quote  
500 mg   Get quote  

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    HG-9-91-01 purchased from MCE. Usage Cited in: J Biol Chem. 2015 Jul 17;290(29):17879-93.

    Pterosin B does not inhibit SIK3 kinase activity up to 1 mM, whereas the strong pan-SIK inhibitor HG9-91-01 completely inhibits SIK3 kinase activity even at 1 μM. The GST-SIK3 enzyme is expressed in HEK293 cells, purified with a glutathione resin, and incubated with compounds, the coumarin-labeled CRTC2 peptide, and 1 mM ATP for 1 h. The phosphorylated and nonphosphorylated peptides are separated by electrophoresis.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    HG-9-91-01 is a potent and highly selective salt-inducible kinase (SIKs) inhibitor with IC50s of 0.92 nM, 6.6 nM and 9.6 nM for SIK1, SIK2 and SIK3 respectively.

    IC50 & Target

    IC50: 0.92/6.6/9.6 nM (SIK1/2/3)[1]

    In Vitro

    HG-9-91-01 inhibits a number of protein tyrosine kinases that possess a threonine residue at the gatekeeper site, such as Src family members (Src, Lck, and Yes), BTK, and the FGF and Ephrin receptors[1]. HG-9-91-01 demonstrates a strong correlation between the potency of SIK2 inhibition and enhanced IL-10 production. In agreement with these reports, pretreating BMDCs with HG-9-91-01, a recently described inhibitor of SIK1-3, along with several other kinases, results in concentration-dependent potentiation of zymosan-induced IL-10 production with an EC50 ~200 nM and a maximum effect similar to that observed with PGE2[2]. HG-9-91-01 has more than a 100-fold greater potency against SIKs than AMPK (IC50=4.5 μM) in a cell-free assay. HG-9-91-01 treatment dose dependently increased mRNA expression of Pck1 and G6pc and that effect is similar in cells treated with 4 μM HG-9-91-01 or 0.1 μM glucagon. Consistent with this observation, there is also a dose-dependent increase in glucose production following HG-9-91-01 treatment[3].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.7616 mL 8.8078 mL 17.6156 mL
    5 mM 0.3523 mL 1.7616 mL 3.5231 mL
    10 mM 0.1762 mL 0.8808 mL 1.7616 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [2]

    HG-9-91-01 is dissolved in DMSO and stored, and then diluted with appropriate media before use[2].

    Bone marrow is harvested from femurs and tibias of C57BL/6 mice. Bone-marrow-derived dendritic cells (BMDCs) are differentiated DMEM supplemented with 2 mM GlutaMAX, 10% (vol/vol) FBS, Penicillin, Streptomycin, and 2% mouse granulocyte-macrophage colony-stimulating factor (GM-CSF)-conditioned media derived from murine L cells. Cultures are differentiated for 7 d and routinely analyzed for >90% CD11c (allophycocyanin (APC) anti-CD11c clone HL3) positivity by flow cytometry before use in experiments. Lentiviral transduction of bone marrow cultures is conducted by addition of 293T culture supernatants containing lentiviral particles encoding the CREB-dependent luciferase reporter construct or CRTC3 targeting or control shRNAs 1 d postisolation. Stable integration of lentiviral shRNA constructs is selected by addition of puromycin (3 μg/mL) on day 4 posttransduction. After 2 d, stably transduced BMDCs are released from selection and used in subsequent assays. Unless otherwise indicated, cells are treated for 2 d with PGE2 (5 μM) or HG-9-91-01 (0.5 μM) or an equivalent concentration of DMSO (≤0.5%) and then stimulated for 18 h with LPS (100 ng/mL), R848 (10 μg/mL), or Zymosan (4 μg/mL)[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    567.68

    Formula

    C₃₂H₃₇N₇O₃

    CAS No.

    1456858-58-4

    SMILES

    CC1=CC=CC(C)=C1NC(N(C2=NC=NC(NC3=CC=C(N4CCN(C)CC4)C=C3)=C2)C5=CC=C(OC)C=C5OC)=O

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    HG 9-91-01 is dissolved in 30% propylene glycol plus 70% ethanol[4].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

    Purity: >98.0%

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    Product Name:
    HG-9-91-01
    Cat. No.:
    HY-15776
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