| Size | Price | Stock | Qty |
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| 5mg |
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| 50mg |
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| Targets |
WEE1 kinase; WEE1-IN-5 is a potent and highly specific inhibitor of WEE1. WEE1 is a tyrosine kinase that phosphorylates and inactivates CDC2, a key regulator of the G2/M checkpoint. By inhibiting WEE1, the compound prevents the phosphorylation of CDC2, leading to premature entry into mitosis. This abrogates the G2 checkpoint, causing cells with DNA damage to undergo mitotic catastrophe and cell death. The compound enhances the sensitivity of cancer cells to DNA-damaging agents such as carboplatin.
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| ln Vitro |
WEE1-IN-5 in pCDC2 has an EC50 of 188 nM, while CYP3A4/5 has a variable IC50 [1].
In vitro, WEE1-IN-5 potently inhibits WEE1 with an IC₅₀ of 0.8 nM. It inhibits phospho-CDC2, confirming its on-target activity. The compound abrogates the G2 checkpoint, increasing the sensitivity of cancer cells to DNA-damaging agents. It is used in cell-based assays to study the role of WEE1 in cell cycle regulation and DNA damage response. The compound is typically dissolved in DMSO for in vitro studies. |
| ln Vivo |
In SD rats, WEE1-IN-5 (5 mg/kg orally; 1 mg/kg intravenously; single dose) has a bioavailability of 35%, an AUCint of 1324 h·ng/mL, and a CL of 14 mL/min/kg. ..1].
In vivo, WEE1-IN-5 enhances the antitumor activity of carboplatin in animal models. The compound is orally available, making it suitable for oral administration. It abrogates the G2 checkpoint, increasing the sensitivity of tumors to DNA-damaging agents. The compound shows potential as an anticancer agent, particularly in combination with chemotherapy. It is being studied for its ability to enhance the efficacy of DNA-damaging agents in cancer treatment. |
| Enzyme Assay |
In vitro, cancer cell lines are treated with WEE1-IN-5 at various concentrations, and cell viability is measured using standard assays such as MTT or CellTiter-Glo. The inhibition of WEE1 kinase activity is assessed by measuring the phosphorylation of CDC2 using Western blotting. The abrogation of the G2 checkpoint is evaluated by flow cytometry analysis of cell cycle distribution. The compound is typically dissolved in DMSO and diluted in cell culture medium. The IC₅₀ for WEE1 inhibition is determined by kinase activity assays.
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| Animal Protocol |
In vivo, WEE1-IN-5 is administered orally to tumor-bearing mice. The compound is typically given daily or on a schedule that optimizes its antitumor activity. Tumor growth is monitored over time, and the compound's ability to enhance the efficacy of carboplatin or other DNA-damaging agents is assessed. The animals are evaluated for tumor regression, survival, and toxicity. All procedures are conducted in accordance with institutional animal care guidelines.
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| ADME/Pharmacokinetics |
WEE1-IN-5 has a molecular weight of 511.45 and the chemical formula C₂₆H₂₈Cl₂N₆O. It is orally available, indicating good oral bioavailability. The compound is soluble in DMSO. It should be stored at -20°C. The compound is for research use only and not for human therapeutic use. Further studies are needed to fully characterize its ADME properties.
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| Toxicity/Toxicokinetics |
Specific toxicity data for WEE1-IN-5 are not extensively documented. As a WEE1 inhibitor, it may cause cell death in proliferating cells, particularly those with DNA damage. The compound is for research use only and not for human therapeutic use. It should be handled with appropriate safety precautions, including the use of personal protective equipment. The compound should be stored in a sealed container in a cool, dry place away from incompatible materials.
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| References | |
| Additional Infomation |
WEE1-IN-5 is also known as Debio-0123. It is a potent, orally available, and highly specific WEE1 inhibitor with an IC₅₀ in the low nanomolar range. It inhibits phospho-CDC2 and abrogates the G2 checkpoint, increasing sensitivity to DNA-damaging agents. It enhances the antitumor activity of carboplatin in vivo. It is used in cancer research to study the role of WEE1 in cell cycle regulation and DNA damage response. It is supplied as a solid and should be stored at -20°C. It is for research use only.
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| Molecular Formula |
C26H28CL2N6O
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|---|---|
| Molecular Weight |
511.4461
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| Exact Mass |
510.17
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| CAS # |
2243882-74-6
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| PubChem CID |
152206257
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| Appearance |
White to off-white solid powder
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| Density |
1.331±0.06 g/cm3(Predicted)
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| Boiling Point |
684.4±65.0 °C(Predicted)
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
727
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VWHNEYAANMETIA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H28Cl2N6O/c1-16-13-18(7-8-19(16)17-9-11-32(2)12-10-17)30-26-29-14-20-24(31-26)33(3)15-34(25(20)35)23-21(27)5-4-6-22(23)28/h4-8,13-14,17H,9-12,15H2,1-3H3,(H,29,30,31)
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| Chemical Name |
6-(2,6-dichlorophenyl)-8-methyl-2-[3-methyl-4-(1-methylpiperidin-4-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one
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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 : ~20 mg/mL (~39.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.96 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (1.96 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 10.0 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: ≥ 1 mg/mL (1.96 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 | 1.9552 mL | 9.7761 mL | 19.5523 mL | |
| 5 mM | 0.3910 mL | 1.9552 mL | 3.9105 mL | |
| 10 mM | 0.1955 mL | 0.9776 mL | 1.9552 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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