| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
GNE-900 targets ChK1 as a potent and selective inhibitor. It inhibits ChK1 with an IC₅₀ of 1.1 nM and ChK2 with an IC₅₀ of 1.5 µM. By inhibiting ChK1, the compound abrogates the G2-M checkpoint, preventing DNA damage repair and inducing apoptosis.
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|---|---|
| ln Vitro |
When combined with gemcitabine (50 nM), GNE-900 (1 µM; 1-48 h) induces and increases local PARP expression in HT-29 cells [1].Cell
In vitro, GNE-900 enhances DNA damage and induces apoptosis in cancer cells. It abrogates the G2-M checkpoint, sensitizing cells to DNA-damaging agents. The compound has anti-tumor activity. Combination with gemcitabine shows enhanced anti-tumor activity. |
| ln Vivo |
When paired with gemcitabine, GNE-900 (2.5–40 mg/kg; po; once) can decrease tumor volume while increasing DNA damage and γ-H2AX expression levels in malignancies [1].
In vivo, GNE-900 is orally active and has demonstrated anti-tumor activity. Combination with gemcitabine shows anti-tumor activity in xenograft models. The compound's oral bioavailability makes it suitable for in vivo studies. |
| Enzyme Assay |
ChK1 kinase assays: Recombinant ChK1 and ChK2 enzymes are incubated with peptide substrates and ATP in the presence of GNE-900 at various concentrations (typically 0.1-1000 nM). Kinase activity is measured by detecting phosphorylated substrate using radioactive or fluorescence-based detection. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Apoptosis analysis [1]
Cell Types: HT-29 Cell Tested Concentrations: 1 µM Incubation Duration: 1-48 hrs (hours) Experimental Results: Induces apoptosis and increases expression of cleaved PARP when combined with gemcitabine (50 nM). Cancer cell lines are cultured in appropriate media at 37°C with 5% CO₂. Cells are treated with GNE-900 at various concentrations (typically 1 nM-10 µM), alone or in combination with DNA-damaging agents such as gemcitabine. Cell viability is assessed by MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining and caspase activity assays. Cell cycle analysis is performed by flow cytometry. |
| Animal Protocol |
Animal/Disease Models: SD (SD (Sprague-Dawley)) rat (HT-29 tumor xenograft) [1]
Doses: 2.5-40 mg/kg (received gemcitabine dose 120 mg/kg) Route of Administration: Po; Experimental Results: Tumor volume diminished, DNA damage was Dramatically enhanced and γ-H2AX levels increased. In vivo efficacy studies are conducted in tumor xenograft models. GNE-900 is administered orally at specified doses. Tumor growth is monitored over time. Combination studies with gemcitabine are performed. Pharmacokinetic parameters are assessed by measuring compound concentrations in plasma. Tumor tissues are analyzed for apoptosis markers and DNA damage. |
| ADME/Pharmacokinetics |
GNE-900 has molecular weight 367.45 and formula C₂₃H₂₁N₅. It is soluble in DMSO (3.85 mg/mL, 10.48 mM). For in vivo formulation, 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline: 1 mg/mL (2.72 mM) is recommended. Purity is 99.20%.
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| References | |
| Additional Infomation |
GNE-900 is an ATP-competitive, selective, and orally active ChK1 inhibitor. It inhibits ChK1 with an IC₅₀ of 1.1 nM, displaying >300-fold selectivity over ChK2 and other kinases. The compound abrogates the G2-M checkpoint, enhances DNA damage, and induces apoptosis. Combination with gemcitabine shows anti-tumor activity.
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| Molecular Formula |
C23H21N5
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|---|---|
| Molecular Weight |
367.45
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| Exact Mass |
367.179
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| CAS # |
1200126-26-6
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| PubChem CID |
44545757
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| Appearance |
Light yellow to brown solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
633.4±55.0 °C at 760 mmHg
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| Flash Point |
336.9±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.727
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| LogP |
4.44
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
571
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(NC5=C4C=C(N=C5)C#N)N=C3
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| InChi Key |
PPYHOOZGDDPLKM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21N5/c24-12-19-11-20-21-10-18(13-26-23(21)27-22(20)14-25-19)17-6-4-16(5-7-17)15-28-8-2-1-3-9-28/h4-7,10-11,13-14H,1-3,8-9,15H2,(H,26,27)
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| Chemical Name |
12-[4-(piperidin-1-ylmethyl)phenyl]-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene-4-carbonitrile
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| Synonyms |
GNE 900 GNE-900 GNE900
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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: ~100 mg/mL (~272.2 mM; with ultrasonication and warming by heating to 80°C)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.80 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7215 mL | 13.6073 mL | 27.2146 mL | |
| 5 mM | 0.5443 mL | 2.7215 mL | 5.4429 mL | |
| 10 mM | 0.2721 mL | 1.3607 mL | 2.7215 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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