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| 1mg | ||
| 5mg | ||
| 10mg | ||
| Other Sizes |
| Targets |
SIK2
Salt-inducible kinase 2 (SIK2), also known as SIK2. SIK2 plays crucial roles in regulating cell cycle progression, glucose metabolism, apoptosis, and the Warburg effect in cancer cells. Related family members SIK1 (IC50=0.92 nM) and SIK3 (IC50=9.6 nM) may also be inhibited with varying selectivity, depending on the specific compound. HG-9-91-01 is a highly selective SIK inhibitor with IC50 values of 0.92 nM, 6.6 nM and 9.6 nM for SIK1, SIK2 and SIK3 respectively. |
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| ln Vitro |
In vitro, SIK2-IN-1 exerts its effects by specifically inhibiting the activity of SIK2, disrupting downstream signaling pathways including PI3K-Akt-mTOR, Hippo-YAP, and cAMP-PKA. In ovarian cancer cells, SIK2 promotes glucose metabolism and enhances the Warburg effect via PI3K/AKT pathway. SIK2-IN-1 leads to reduced cell proliferation and increased apoptosis. In breast cancer, SIK2 acts as a tumor suppressor, and SIK2-IN-1 modulates this activity.
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| ln Vivo |
In vivo, SIK2 overexpression has been shown to result in smaller tumor sizes in xenograft models, indicating the therapeutic promise of SIK2 modulators. SIK2-IN-1 has implications in metabolic regulation, particularly concerning lipid metabolism and insulin sensitivity. It regulates fatty acid synthesis and glucose metabolism, making it a target for diabetes research. Further in vivo efficacy studies are ongoing.
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| Enzyme Assay |
SIK2 kinase activity assay protocol: Recombinant human SIK2 is incubated with increasing concentrations of SIK2-IN-1 (0-1000 nM) in reaction buffer (40 mM Tris-HCl pH 7.5, 20 mM MgCl2, 0.1 mg/mL BSA, 50 uM ATP) with a peptide substrate (e.g., AMARA peptide) for 30 min at 30degC. Kinase activity is measured using ADP-Glo or radiometric [gamma-33P]-ATP incorporation. The IC50 is calculated by non-linear regression analysis from triplicate measurements.
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| Cell Assay |
Cell proliferation assay protocol: Cancer cells (e.g., ovarian OVCAR3 or breast MDA-MB-231 cells) are seeded in 96-well plates (5,000 cells/well) and cultured overnight. Cells are treated with SIK2-IN-1 at concentrations ranging from 0-100 uM for 48-72 hours. Cell viability is measured using MTT or CellTiter-Glo assay. For signaling studies, cells are treated with SIK2-IN-1 (0-10 uM) for 2-24 hours, lysed, and analyzed by Western blotting for p-AKT, p-mTOR, p-CREB, and p-YAP.
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| Animal Protocol |
Xenograft tumor model protocol (example): Female BALB/c nude mice (6-8 weeks old) are subcutaneously implanted with ovarian cancer cells (5×10⁶ cells/mouse). When tumors reach ~100-150 mm3, mice are randomized into groups (n=6-8). SIK2-IN-1 is administered intraperitoneally or orally at doses of 10-50 mg/kg, daily for 14-21 days. Tumor volume is measured every 2-3 days using calipers. Tumor tissues are collected for immunohistochemistry (Ki-67, cleaved caspase-3) and Western blotting.
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| ADME/Pharmacokinetics |
PK data for SIK2-IN-1 are not detailed in the literature. As a small molecule (MW 547.6), it is expected to have reasonable oral bioavailability and tissue distribution. Solubility should be evaluated in DMSO, PEG300, or other suitable vehicles. Pharmacokinetic parameters (half-life, Cmax, AUC, clearance) can be determined in rodent models via LC-MS/MS after intravenous or oral administration at doses of 1-10 mg/kg.
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| Toxicity/Toxicokinetics |
Toxicity data for SIK2-IN-1 are limited. The compound is intended for research use only and not for human therapeutic applications. Based on its mechanism of inhibiting SIK2, which regulates metabolic pathways and cell survival, potential on-target toxicities could include metabolic disturbances. Standard laboratory safety precautions should be observed when handling this compound.
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| References |
[1]. Zhu W, et al. Discovery of novel and selective SIK2 inhibitors by the application of AlphaFold structures and generative models. Bioorg Med Chem. 2023 Jul 13;91:117414.
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| Additional Infomation |
SIK2-IN-1 is a research compound that has not entered clinical trials or received regulatory approval. Salt-inducible kinases (SIKs) are emerging targets for the treatment of inflammatory and autoimmune diseases such as psoriasis, as well as metabolic disorders and certain cancers. GLPG3970 is a first-in-class SIK2/SIK3 inhibitor in clinical development. SIK2-IN-1 is a valuable tool for preclinical research on SIK family biology.
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| Molecular Formula |
C25H28F3N7O2S
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| Appearance |
Typically exists as solid at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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