| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
GNE-220 HCl primarily targets MAP4K4 (also known as HGK), a serine/threonine kinase belonging to the GCK family of STE20 kinases. It also inhibits several other kinases with lower potency, including MINK (MAP4K6) with an IC50 of 9 nM, DMPK with an IC50 of 476 nM, and KHS1 (MAP4K5) with an IC50 of 1.1 μM. The compound shows selectivity for MAP4K4 over these related kinases. MAP4K4 is involved in regulating cell migration, cytoskeletal dynamics, and inflammatory responses. Inhibition of MAP4K4 by GNE-220 HCl disrupts downstream signaling pathways that control membrane protrusion and cell motility.
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| ln Vitro |
GNE-220 also has the ability to inhibit a number of other kinases; its IC50 values for MINK (MAP4K6), DMPK, and KHS1 (MAP4K5) are 9 nM, 476 nM, and 1.1 μM, respectively. The sprouting morphology of human umbilical vein endothelial cells (HUVECs) is altered by GNE-220. In a dose-dependent manner, GNE-220 also decreased pERM+ retractile fibers. Additionally, GNE-220 increases the number of active INTβ1+ focal adhesions (FA) in a dose-dependent manner. [1]
GNE-220 HCl demonstrates potent in vitro activity against MAP4K4 with an IC50 of 7 nM in enzymatic assays. In human umbilical vein endothelial cells (HUVEC), GNE-220 alters sprout morphology and reduces pERM+ retraction fibers in a dose-dependent manner. The compound also dose-dependently increases the number of active-INTβ1+ long focal adhesions (FAs). These effects are consistent with the role of MAP4K4 in regulating membrane dynamics during cell migration. The compound modulates the MAP4K4-moesin-talin-β1-integrin molecular pathway, which promotes efficient plasma membrane contraction during endothelial cell migration. |
| ln Vivo |
GNE-220 HCl has been evaluated in in vivo models of angiogenesis and cell migration. In vascular endothelial growth factor (VEGF)-stimulated angiogenesis models, inhibition of MAP4K4 using chemical inhibitors such as GNE-220 HCl reduces membrane dynamics and impairs endothelial cell migration. Short interfering RNA (siRNA) knockdown studies have been used in conjunction with GNE-220 HCl to validate the role of MAP4K4 in these processes. The compound is suitable for in vivo administration to study the functional consequences of MAP4K4 inhibition on physiological and pathological angiogenesis, though detailed pharmacokinetic parameters and specific in vivo efficacy data are limited in publicly available sources.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cell-based) assay for GNE-220 HCl typically involves a biochemical kinase activity assay using recombinant MAP4K4 enzyme. The assay measures the inhibition of kinase activity by quantifying the phosphorylation of a peptide substrate in the presence of ATP. IC50 values are determined by incubating varying concentrations of GNE-220 HCl with the enzyme and substrate, followed by detection using techniques such as fluorescence polarization, luminescence, or radiometric measurement. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. The reaction is initiated by the addition of ATP and terminated after a fixed incubation period. Dose-response curves are generated and fitted to calculate the IC50 value of 7 nM.
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| Cell Assay |
The in vitro cellular assay for GNE-220 HCl is performed using human umbilical vein endothelial cells (HUVEC) cultured in appropriate endothelial growth medium. Cells are seeded onto extracellular matrix-coated surfaces and allowed to adhere. Following serum starvation to synchronize the cell cycle, cells are treated with varying concentrations of GNE-220 HCl (typically in the nanomolar to micromolar range) or vehicle control (DMSO). Cells are then stimulated with VEGF or other pro-angiogenic factors to induce sprouting and migration. Endothelial sprout morphology is assessed by microscopy, and retraction fibers are quantified by immunofluorescence staining for phospho-ERM (ezrin/radixin/moesin) proteins. Active integrin β1-positive focal adhesions are also visualized and counted. Dose-response relationships are established by analyzing morphological changes across different compound concentrations.
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| Animal Protocol |
In vivo animal experiments with GNE-220 HCl typically utilize mouse or rat models of angiogenesis, such as the Matrigel plug assay, retinal angiogenesis models, or tumor xenograft models. The compound is administered via intraperitoneal (IP) or oral (PO) routes, with dosing schedules and concentrations determined based on preliminary pharmacokinetic studies. For angiogenesis studies, animals are implanted with Matrigel containing VEGF and test compound, and neovascularization is assessed after 7-14 days by hemoglobin content or CD31 immunostaining. In tumor models, GNE-220 HCl is administered daily or on a scheduled basis, and tumor volume is measured periodically. Endpoints include tumor growth inhibition, microvessel density, and analysis of signaling pathway biomarkers (e.g., phospho-ERM, integrin activation) in harvested tissues. Pharmacodynamic evaluations are conducted to confirm target engagement.
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| ADME/Pharmacokinetics |
Comprehensive pharmacokinetic (PK) data for GNE-220 HCl are not extensively reported in publicly available literature. As a small-molecule kinase inhibitor, the compound is expected to have moderate oral bioavailability and reasonable plasma protein binding. GNE-220 HCl is soluble in DMSO (5.4 mg/mL) and water (5 mg/mL), enabling formulation for both in vitro and in vivo studies. For in vivo administration, the compound is typically formulated using appropriate vehicles such as PEG300, Tween 80, or carboxymethyl cellulose (CMC) to ensure adequate solubility and stability. The compound should be stored at -20°C in a dry, dark environment for long-term stability, with stock solutions stable at 0-4°C for up to one month. Detailed parameters such as half-life, clearance, volume of distribution, and maximum concentration (Cmax) require further investigation.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for GNE-220 HCl are not extensively documented in publicly available sources. As a research-grade chemical inhibitor, the compound is classified for research use only and is not intended for diagnostic, therapeutic, or human use. Standard safety precautions should be observed when handling GNE-220 HCl, including the use of appropriate personal protective equipment (PPE) and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. For in vivo studies, toxicity assessments should be conducted as part of the experimental design, including monitoring of body weight, general health status, and histopathological examination of major organs following compound administration. No specific toxicity data (e.g., LD50, maximum tolerated dose) are available from the current search results.
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| References | |
| Additional Infomation |
GNE-220 HCl is a research compound developed for studying the biological functions of MAP4K4 in cell migration and angiogenesis. The MAP4K4-moesin-talin-β1-integrin pathway identified using this inhibitor represents a potential therapeutic target for diseases involving aberrant angiogenesis, such as cancer, diabetic retinopathy, and inflammatory disorders. GNE-220 HCl is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical research. The compound is available from various chemical suppliers for research purposes. Further studies are needed to fully characterize its selectivity profile, pharmacokinetic properties, and therapeutic potential. The compound's utility lies in its ability to selectively inhibit MAP4K4 and dissect its role in cytoskeletal dynamics and cell motility.
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| Molecular Formula |
C25H27CLN8
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|---|---|
| Molecular Weight |
474.988482713699
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| Exact Mass |
474.204
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| CAS # |
2448286-21-1
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| Related CAS # |
GNE 220;1199590-75-4
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| PubChem CID |
134828260
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
34
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| Complexity |
661
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.N1(C2C=CC(C3=CN=C4C(=C3)C3=C(C(C)=NC(C5C=NN(C)C=5)=N3)N4)=CC=2)CCN(C)CC1
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| InChi Key |
VBVBAEHNBOTZQV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H26N8.ClH/c1-16-22-23(30-24(28-16)19-14-27-32(3)15-19)21-12-18(13-26-25(21)29-22)17-4-6-20(7-5-17)33-10-8-31(2)9-11-33;/h4-7,12-15H,8-11H2,1-3H3,(H,26,29);1H
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| Chemical Name |
6-methyl-12-[4-(4-methylpiperazin-1-yl)phenyl]-4-(1-methylpyrazol-4-yl)-3,5,8,10-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~5.4 mg/mL (~11.37 mM)
H2O : ~5 mg/mL (~10.53 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.54 mg/mL (1.14 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 5.4 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: ≥ 0.54 mg/mL (1.14 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 5.4 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: ≥ 0.54 mg/mL (1.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 11.11 mg/mL (23.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1053 mL | 10.5265 mL | 21.0531 mL | |
| 5 mM | 0.4211 mL | 2.1053 mL | 4.2106 mL | |
| 10 mM | 0.2105 mL | 1.0527 mL | 2.1053 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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