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| Targets |
The compound has no single specific target; it is a pan-kinase inhibitor, meaning it is designed to bind to the highly conserved ATP-binding pocket found in many protein kinases. It interacts with a broad panel of kinases, inhibiting their activity. It is a non-selective tool used for "off-target" profiling and to study the kinase interaction network. It is also reported to be a selective inhibitor of BRD4.
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| ln Vitro |
GSK3182571 is not a highly potent inhibitor of a specific kinase but rather a versatile probe. Its main in vitro utility is in the thermal proteome profiling (TPP) experiment. In this assay, it is used at a single high concentration (e.g., 20 microM) to induce melting temperature (Tm) shifts in many kinases at once. In K562 cell extracts, it significantly changed the Tm of 51 kinases, and these shifts correlated with pIC50 values, allowing for proteome-wide assessment of target engagement.
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| ln Vivo |
There are no reported in vivo studies for GSK3182571. Given its non-selectivity, it would likely have significant off-target toxicity, making it unsuitable for standard animal efficacy studies. Its primary application is as an ex vivo tool in lysates or as an in-cell probe to study the cellular thermal shift of kinases. It can be used in leukemia cell models to explore drug effects on the kinase network and off-target effects.
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| Enzyme Assay |
The primary application of this compound is in the thermal proteome profiling (TPP) assay. This cell-free assay is performed by incubating K562 cell lysates with either DMSO (control) or 20 microM GSK3182571. The lysates are then heated at a range of temperatures (e.g., 37-67 degC). After heating, the soluble (non-aggregated) proteins are separated from the pellet. The soluble proteins are then digested with trypsin and the resulting peptides are analyzed by mass spectrometry. The melting temperature (Tm) of thousands of proteins can be quantified simultaneously. The compound induces a Tm shift for proteins it binds to, revealing its targets directly in a complex biological matrix.
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| Cell Assay |
A cellular thermal shift assay (CETSA) can be performed to confirm target engagement in live cells. Intact K562 cells are treated with the compound or DMSO control. The cells are then collected and heated to various temperatures. After heating, the cells are lysed, and the soluble protein fraction is collected. The target protein of interest (e.g., BRD4) is then quantified via a specific Western blot. An increase in the thermal stability of the protein in the compound-treated sample indicates direct engagement in the cellular context.
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| Animal Protocol |
No animal experiments are specifically reported for GSK3182571. It is a tool compound used primarily for in vitro proteomics. If an in vivo study were to be designed, it would likely involve administration of the compound to tumor-bearing mice to assess its effect on the thermal stability of its target proteins (e.g., BRD4) in the tumor tissue. This would be a CETSA performed on in vivo tissue samples, but this is not standard for this compound.
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| ADME/Pharmacokinetics |
GSK3182571 is a small molecule with a molecular weight of 495.02 g/mol and a LogP value indicating moderate lipophilicity. The specific PK properties are not reported, but as a research tool, it can be dissolved in DMSO and then further diluted in common vehicles for in vitro assays. It is structurally similar to CTx-0294885, a highly soluble and potent kinase inhibitor, suggesting it may have favorable properties for cellular uptake.
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| Toxicity/Toxicokinetics |
As a non-selective, broad-spectrum kinase inhibitor, GSK3182571 is expected to have significant potential for off-target toxicity. Kinases are involved in countless cellular processes, and inhibiting many at once could lead to a wide range of cytotoxic effects. The compound should be treated as a hazardous material. Toxicity studies are not relevant for its intended use as a proteomics probe, and no data is provided by suppliers.
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| References |
[1]. Mikhail M Savitski, et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science. 2014 Oct 3;346(6205):1255784.
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| Additional Infomation |
GSK3182571 is a research-grade chemical probe used primarily in thermal proteome profiling (TPP) and cellular thermal shift assays (CETSA). These cutting-edge techniques use thermal stability as a readout for drug-target engagement. The compound serves as a valuable tool to identify the direct protein targets and off-targets of drugs in a complex cellular environment, which is a major challenge in drug discovery. It is also used to study the effects on kinase networks in leukemia cell models. It is not a clinical candidate and has no therapeutic approval. There is conflicting information; some sources list it as a pan-kinase inhibitor, while others list it as a selective BRD4 inhibitor.
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| Molecular Formula |
C25H31CLN8O
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|---|---|
| Molecular Weight |
495.0196
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| Exact Mass |
494.23
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| CAS # |
2135595-04-7
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| PubChem CID |
139033556
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| Appearance |
White to light yellow solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
35
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| Complexity |
641
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CNC(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=CC=C(C=C3)N4CCN(CC4)CCCN
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| InChi Key |
UJADJYISGUHANC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H31ClN8O/c1-28-24(35)20-5-2-3-6-22(20)31-23-21(26)17-29-25(32-23)30-18-7-9-19(10-8-18)34-15-13-33(14-16-34)12-4-11-27/h2-3,5-10,17H,4,11-16,27H2,1H3,(H,28,35)(H2,29,30,31,32)
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| Chemical Name |
2-[[2-[4-[4-(3-aminopropyl)piperazin-1-yl]anilino]-5-chloropyrimidin-4-yl]amino]-N-methylbenzamide
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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) |
DMSO: 100 mg/mL (202.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0201 mL | 10.1006 mL | 20.2012 mL | |
| 5 mM | 0.4040 mL | 2.0201 mL | 4.0402 mL | |
| 10 mM | 0.2020 mL | 1.0101 mL | 2.0201 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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