HG-9-91-01 [1456858-58-4]

Cat# HY-15776-5mg

Size : 5mg

Brand : MedChemExpress

Contact local distributor :


Phone : +1 850 650 7790

HG-9-91-01 is a potent and highly selective salt-inducible kinase (SIK) 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

This product is a controlled substance and not for sale in your territory.

Based on 25 publication(s) in Google Scholar

    HG-9-91-01 purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2019 Jan 15;508(3):775-779.  [Abstract]

    Differentiated 3T3-L1 adipocytes are treated with different doses of HG-9-91-01, western analysis of protein expression is showed.

    HG-9-91-01 purchased from MedChemExpress. Usage Cited in: Kansai University. 2017 Mar.

    Pterosin B quickly induces the dephosphorylation of CRTC2 in AML-12 cells, which is also observed in Fsk- and HG9-91-01-treated cells.

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

    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.

    View All Salt-inducible Kinase (SIK) Isoform Specific Products:

    View All Isoforms
    SIK1 SIK2 SIK3
    Description

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

    IC50 & Target

    SIK1

     

    SIK2

     

    SIK3

     

    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. Consistent with this observation, there is also a dose-dependent increase in glucose production following HG-9-91-01 treatment[3].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Molecular Weight

    567.68

    Formula

    C32H37N7O3

    CAS No.

    1456858-58-4

    Appearance

    Solid

    Color

    White to yellow

    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

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 150 mg/mL (264.23 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent 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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.40 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.08 mg/mL (3.66 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.77%

    References
    • [1]. Clark K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated andregulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91.  [Content Brief]

      [2]. Sundberg TB, et al. Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells. Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12468-73.  [Content Brief]

      [3]. Patel K, et al.The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver. Nat Commun. 2014 Aug 4;5:4535.  [Content Brief]

    Cell Assay
    [2]

    Bone marrow is harvested from femurs and tibias of C57BL/6 mice. Bone-marrow-derived dendritic cells (BMDCs) are differentiated DMEM. 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
    • [1]. Clark K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated andregulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91.  [Content Brief]

      [2]. Sundberg TB, et al. Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells. Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12468-73.  [Content Brief]

      [3]. Patel K, et al.The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver. Nat Commun. 2014 Aug 4;5:4535.  [Content Brief]

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.7616 mL 8.8078 mL 17.6156 mL 44.0389 mL
    5 mM 0.3523 mL 1.7616 mL 3.5231 mL 8.8078 mL
    10 mM 0.1762 mL 0.8808 mL 1.7616 mL 4.4039 mL
    15 mM 0.1174 mL 0.5872 mL 1.1744 mL 2.9359 mL
    20 mM 0.0881 mL 0.4404 mL 0.8808 mL 2.2019 mL
    25 mM 0.0705 mL 0.3523 mL 0.7046 mL 1.7616 mL
    30 mM 0.0587 mL 0.2936 mL 0.5872 mL 1.4680 mL
    40 mM 0.0440 mL 0.2202 mL 0.4404 mL 1.1010 mL
    50 mM 0.0352 mL 0.1762 mL 0.3523 mL 0.8808 mL
    60 mM 0.0294 mL 0.1468 mL 0.2936 mL 0.7340 mL
    80 mM 0.0220 mL 0.1101 mL 0.2202 mL 0.5505 mL
    100 mM 0.0176 mL 0.0881 mL 0.1762 mL 0.4404 mL
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.

    HG-9-91-01 Related Classifications

    Help & FAQs

    Keywords:

    HG-9-91-011456858-58-4SIK inhibitor 1SIK inhibitor1SIK inhibitor-1Salt-inducible Kinase (SIK)Inhibitorinhibitorinhibit

    You might also be interested by the following products:



    Cat#
    Description
    Cond.
    Price Bef. VAT
    SY-A66-1mg
     1 mg 
    HY-10254-100mg
     100mg