| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
CHK1-IN-4 targets checkpoint kinase 1 (CHK1), a serine/threonine protein kinase that regulates the G2/M cell cycle checkpoint and DNA damage response. CHK1 inhibitors abrogate the G2 checkpoint, forcing cancer cells into premature mitosis, leading to mitotic catastrophe and apoptosis.
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| ln Vitro |
In vitro, CHK1-IN-4 potently inhibits CHK1 phosphorylation in tumor cells. It demonstrates anti-tumor activity across various cancer cell lines. By blocking CHK1 activity, the compound prevents DNA damage repair and induces cell cycle progression despite DNA damage, resulting in selective cancer cell death. Specific IC₅0 values for CHK1 enzymatic inhibition have not been published for this compound.
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| ln Vivo |
In vivo, CHK1-IN-4 hydrochloride has demonstrated anti-tumor activity in animal models. The compound enhances the efficacy of DNA-damaging chemotherapeutic agents such as gemcitabine, cisplatin, and irinotecan. Detailed in vivo efficacy data (e.g., xenograft studies, tumor growth inhibition) for this specific compound require further literature review.
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| Enzyme Assay |
For CHK1 kinase assays, recombinant human CHK1 enzyme (0.5-5 ng/microL) is incubated with CHK1-IN-4 hydrochloride (0.1-1000 nM) in kinase buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Tween-20) at room temperature for 30 minutes. The reaction is initiated by adding ATP (10 microM) and a CHK1 peptide substrate (e.g., biotinylated Cdc25C peptide, 1-5 microM). After 60 minutes, the reaction is stopped, and phosphorylated product is quantified by time-resolved fluorescence (TR-FRET) using a phospho-specific antibody. IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
For cellular assays, cancer cell lines (e.g., HeLa, HT-29, HCT116, or PANC-1) are seeded in 96-well plates (5,000-10,000 cells/well) and treated with CHK1-IN-4 hydrochloride (0.1-10 microM) alone or in combination with DNA-damaging agents (e.g., gemcitabine 10-100 nM, cisplatin 1-10 microM) for 48-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assays. CHK1 phosphorylation status is measured by Western blot using anti-p-CHK1 (Ser345) antibody. Cell cycle analysis is performed by propidium iodide staining and flow cytometry (G2/M checkpoint abrogation indicated by reduced G2 fraction and increased polyploidy). Apoptosis is assessed by Annexin V/PI staining and caspase-3/7 activity assays. Combination index (CI) values are calculated using Chou-Talalay method to assess synergy.
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| Animal Protocol |
For xenograft studies, immunocompromised mice (e.g., nude mice) bearing subcutaneous human tumor xenografts (e.g., HT-29 colorectal cancer or PANC-1 pancreatic cancer) are treated with CHK1-IN-4 hydrochloride (typically 10-50 mg/kg via intraperitoneal injection) alone or in combination with gemcitabine (50-100 mg/kg IP, twice weekly) for 2-4 weeks. Tumor volumes are measured with calipers. Tumor growth inhibition (TGI) is calculated as 1 - (Treated deltaT/Control deltaT). Body weight is monitored for toxicity. At study termination, tumors are harvested for Western blot (CHK1 phosphorylation, gammaH2AX, cleaved PARP) and histology (H&E, Ki-67, TUNEL).
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties for CHK1-IN-4 hydrochloride are not fully published. As a small molecule kinase inhibitor, it is expected to have moderate oral bioavailability. Solubility in DMSO is good. Further PK characterization including half-life, clearance, and volume of distribution requires additional studies. Formulation for IP injection typically involves DMSO/PEG300/saline mixtures.
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| Toxicity/Toxicokinetics |
Toxicity data for CHK1-IN-4 hydrochloride are limited. CHK1 inhibitors as a class can cause bone marrow suppression, gastrointestinal toxicity, and fatigue. At therapeutic doses, the compound is expected to be tolerated in rodent studies. Severe toxicity may occur at high doses or in combination with chemotherapy. Full toxicological characterization including MTD, NOAEL, and organ-specific toxicity is required for therapeutic development.
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| References | |
| Additional Infomation |
CHK1-IN-4 hydrochloride is a research compound for studying CHK1 inhibition in cancer therapy. It has not received regulatory approval for any clinical indication. The compound is for research use only and is not for diagnostic or therapeutic applications. Potential clinical applications include combination therapy with DNA-damaging chemotherapeutic agents for treating pancreatic, colorectal, and ovarian cancers.
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| Molecular Formula |
C18H19BRCLN7O2
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|---|---|
| Molecular Weight |
480.75
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| Appearance |
Solid Powder
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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: (1). 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 mg/mL (~10.40 mM; with heating and sonication)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0801 mL | 10.4004 mL | 20.8008 mL | |
| 5 mM | 0.4160 mL | 2.0801 mL | 4.1602 mL | |
| 10 mM | 0.2080 mL | 1.0400 mL | 2.0801 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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