| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
The primary target of TCS 2312 is checkpoint kinase 1 (Chk1), a serine/threonine kinase that regulates cell cycle checkpoints in response to DNA damage. By inhibiting Chk1, TCS 2312 abrogates the G2/M checkpoint, forcing cells with damaged DNA to enter mitosis prematurely, leading to mitotic catastrophe and apoptosis.
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|---|---|
| ln Vitro |
In vitro, TCS 2312 inhibits Chk1 with a Ki of 0.38 nM and an EC50 of 60 nM. It is highly selective for Chk1 over other kinases. When combined with gemcitabine, it significantly enhances cell killing in breast and prostate cancer cell lines, demonstrating potent chemosensitization effects.
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| ln Vivo |
In vivo, TCS 2312 has been evaluated in preclinical cancer models. Chk1 inhibition potentiates the antitumor activity of DNA-damaging agents such as gemcitabine. Detailed in vivo efficacy data including dosing regimens, tumor growth inhibition, and pharmacokinetic parameters are limited in the available literature.
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| Enzyme Assay |
Chk1 kinase inhibition assays use recombinant Chk1 enzyme and a fluorescent peptide substrate. TCS 2312 is incubated with the enzyme and substrate in kinase buffer, and Chk1 activity is measured by fluorescence polarization or coupled enzyme assays to determine Ki and EC50 values.
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| Cell Assay |
Cell-based assays use breast and prostate cancer cell lines such as MDA-MB-231 or PC-3. Cells are pretreated with TCS 2312 (typically 250 nM) for 2 hours, followed by gemcitabine treatment. Cell viability and apoptosis are assessed by MTT assays and flow cytometry.
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| Animal Protocol |
In vivo studies use tumor xenograft models in mice. TCS 2312 is administered intraperitoneally or orally at doses determined by pharmacokinetic studies. Tumor growth inhibition, Chk1 target engagement in tumor tissue, and combination efficacy with gemcitabine are evaluated.
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| References |
| Molecular Formula |
C25H24N4O2
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|---|---|
| Exact Mass |
412.19
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| CAS # |
838823-31-7
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| Appearance |
White to off-white solid powder
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| LogP |
5.614
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| SMILES |
OC1=CC(O)=CC=C1C2=CC=C(C3=NNC(NC4=CC=C(CNC5CC5)C=C4)=C3)C=C2
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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). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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: ~8 mg/mL (~19.4 mM; with ultrasonication and warming)
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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.) |
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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