HG-9-91-01
Based on 26 publication(s) in Google Scholar
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.
- Purity: 99.77%
- CAS No.: 1456858-58-4
- Formula: C32H37N7O3
- Molecular Weight:567.68
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Protocol
- Purity & Documentation
- References
-
Help & FAQs
-
Chemical Probe Library
HY-L063
-
Targeted Diversity Library
HY-L099
-
Heterocyclic Compound Library
HY-L138
-
Highly Selective Inhibitors Library
HY-L158
-
Multi-Target Compound Library
HY-L176
-
Bioactive Compound Library Max
HY-L181
-
Kinase Inhibitor Library Mini
HY-L009M
-
MCE Bioactive Compound Library
HY-L001V
-
Bioactive Compound Library
HY-L001
-
High-Throughput Bioactive Compound Library
HY-L205
-
Posttranslational Modification Library
HY-L226
-
Immunology/Inflammation Compound Library
HY-L007
-
Kinase Inhibitor Library
HY-L009
Publications Citing Use of MedChemExpress (MCE) HG-9-91-01
More- Nat Cancer. 2023 May;4(5):754-773. [Abstract]
- Nat Metab. 2021 May;3(5):682-700. [Abstract]
- Nat Commun. 2026 Feb 12;17(1):1214. [Abstract]
- Mol Cell. 2023 Jun 1;83(11):1872-1886.e5. [Abstract]
- Cell Death Dis. 2022 Feb 25;13(2):188. [Abstract]
- Cell Death Dis. 2020 Jan 13;11(1):25. [Abstract]
- Cell Death Dis. 2019 Oct 31;10(11):826. [Abstract]
- Oncogene. 2022 Apr;41(16):2390-2403. [Abstract]
- Cell Rep. 2025 Mar 21;44(4):115456. [Abstract]
- Cell Rep. 2017 Jun 13;19(11):2177-2184. [Abstract]
- JCI Insight. 2022 May 10;e150363. [Abstract]
- Inflamm Bowel Dis. 2021 Oct 20;27(11):1821-1831. [Abstract]
- Mediators Inflamm. 2025 Feb 7:2025:3540219. [Abstract]
- Cell Signal. 2020 Dec:76:109786. [Abstract]
- FASEB J. 2025 Mar 31;39(6):e70393. [Abstract]
- J Biol Chem. 2024 May;300(5):107201. [Abstract]
- J Biol Chem. 2015 Jul 17;290(29):17879-17893. [Abstract]
- J Cell Sci. 2021 Sep 1;134(17):jcs258685. [Abstract]
- J Gen Physiol. 2019 Feb 4;151(2):264-272. [Abstract]
- Biochem Biophys Res Commun. 2019 Jan 15;508(3):775-779. [Abstract]
- Heliyon. 2022 Oct 10;8(10):e11016. [Abstract]
- Patent. US20200246435A1.
- bioRxiv. 2020 Apr.
- Technical University of Munich. 2017 Oct.
- Kansai University. 2017 Mar.
- Elife. 2015 Nov 17:4:e08501. [Abstract]
Customer Validation & Images
-
WB
-
WB
-
WB
Biological Activity
|
SIK1 |
SIK2 |
SIK3 |
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.
Chemical Information
-
CAS No. 1456858-58-4
-
Appearance Solid
-
Molecular Weight 567.68
-
Formula C32H37N7O3
-
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
-
Synonyms
SIK inhibitor 1
-
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
Publications (26)
-
Journal Impact Factor
-
Most Recent
-
Nat Cancer
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias. [Abstract]2023 May;4(5):754-773. PMID: 37237081 -
Nat Metab
In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR. [Abstract]2021 May;3(5):682-700. PMID: 34031592 -
Nat Commun
Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]2026 Feb 12;17(1):1214. PMID: 41680175 -
Mol Cell
2023 Jun 1;83(11):1872-1886.e5. PMID: 37172591 -
Cell Death Dis
Salt-inducible kinases inhibitor HG-9-91-01 targets RIPK3 kinase activity to alleviate necroptosis-mediated inflammatory injury. [Abstract]2022 Feb 25;13(2):188. PMID: 35217652 -
Cell Death Dis
SIK2 enhances synthesis of fatty acid and cholesterol in ovarian cancer cells and tumor growth through PI3K/Akt signaling pathway. [Abstract]2020 Jan 13;11(1):25. PMID: 31932581 -
Cell Death Dis
2019 Oct 31;10(11):826. PMID: 31672960 -
Oncogene
SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/β-catenin signaling. [Abstract]2022 Apr;41(16):2390-2403. PMID: 35277657 -
Cell Rep
2025 Mar 21;44(4):115456. PMID: 40120107 -
Cell Rep
2017 Jun 13;19(11):2177-2184. PMID: 28614705 -
JCI Insight
2022 May 10;e150363. PMID: 35536646 -
Inflamm Bowel Dis
HG-9-91-01 Attenuates Murine Experimental Colitis by Promoting Interleukin-10 Production in Colonic Macrophages Through the SIK/CRTC3 Pathway. [Abstract]2021 Oct 20;27(11):1821-1831. PMID: 33988718 -
Mediators Inflamm
Inhibition of SIK1 Alleviates the Pathologies of Psoriasis by Disrupting IL-17 Signaling. [Abstract]2025 Feb 7:2025:3540219. PMID: 39959414 -
Cell Signal
JUP/plakoglobin is regulated by salt-inducible kinase 2, and is required for insulin-induced signalling and glucose uptake in adipocytes. [Abstract]2020 Dec:76:109786. PMID: 32966883 -
FASEB J
Activation of SIK2 inhibits gluconeogenesis and alleviates lipogenesis-induced inflammatory response by SIK2-CRTC2-ACC1 in hepatocytes of large yellow croaker (Larimichthys crocea). [Abstract]2025 Mar 31;39(6):e70393. PMID: 40067199 -
J Biol Chem
The structures of salt inducible kinase 3 in complex with pharmacological inhibitors reveal determinants for binding and selectivity. [Abstract]2024 May;300(5):107201. PMID: 38508313 -
J Biol Chem
Salt-inducible Kinase 3 Signaling Is Important for the Gluconeogenic Programs in Mouse Hepatocytes. [Abstract]2015 Jul 17;290(29):17879-17893. PMID: 26048985
HG-9-91-01 purchased from MedChemExpress. Usage Cited in: J Biol Chem. 2015 Jul 17;290(29):17879-17893. [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.
-
J Cell Sci
Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation in Drosophila S2 cells. [Abstract]2021 Sep 1;134(17):jcs258685. PMID: 34350957 -
J Gen Physiol
2019 Feb 4;151(2):264-272. PMID: 30606741 -
Biochem Biophys Res Commun
Salt-inducible kinase 2 regulates TFEB and is required for autophagic flux in adipocytes. [Abstract]2019 Jan 15;508(3):775-779. PMID: 30528240
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.
-
Heliyon
Salt-inducible kinase 1 deficiency promotes vascular remodeling in pulmonary arterial hypertension via enhancement of yes-associated protein-mediated proliferation. [Abstract]2022 Oct 10;8(10):e11016. PMID: 36276742 -
-
-
-
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.
-
Elife
Salt-inducible kinases mediate nutrient-sensing to link dietary sugar and tumorigenesis in Drosophila. [Abstract]2015 Nov 17:4:e08501. PMID: 26573956
Solvent & Solubility
DMSO : 250 mg/mL (440.39 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
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.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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.
Protocol
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
-
Data Sheet (280 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Handling Instructions (2659 KB)
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 |
HG-9-91-01 Related Classifications
HY-15776 Related Classifications
Powered by Bioz