| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Targets |
Caspase 3 (IC50 = 10 μM); Thioredoxin (IC50 = 10 μM)
The primary target is the protein-protein interaction between thioredoxin (Trx) and caspase-3. KEA1-97 selectively disrupts this interaction without affecting thioredoxin activity. Thioredoxin is a redox-active protein that plays a role in protecting cells from oxidative stress and also inhibits caspase-3 activity, thereby suppressing apoptosis. By disrupting the Trx-caspase-3 interaction, KEA1-97 relieves the inhibitory effect of thioredoxin on caspase-3, promoting programmed cell death. The compound's selectivity for this specific protein-protein interaction makes it a valuable tool for studying apoptosis regulation. |
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| ln Vitro |
KEA1-97 (100 μM; 231MFP cells) impaires thioredoxin pulldown of caspase 3[1].
KEA1-97 (10 μM; 48 hours; 231MFP cells) inhibits the proliferation of 231MFP serum-free cells[1]. KEA1-97 (10 μM; 0~12 hours; 231MFP cells) activates caspase 3/7 and induces apoptotic cell death[1]. KEA1-97 (231MFP cells) is resistant to impairments in survival and proliferation[1]. KEA1-97 disrupts the interaction of thioredoxin with caspase 3 with an IC50 of 10 μM. This disruption activates caspases and induces apoptosis in cells. Importantly, the compound achieves this without affecting thioredoxin activity, suggesting that it specifically interferes with the protein-protein interaction rather than inhibiting the enzyme's function. The activation of caspases leads to the characteristic biochemical and morphological changes associated with apoptosis, including DNA fragmentation, cell shrinkage, and membrane blebbing. |
| ln Vivo |
KEA1-97 (5 mg/kg; i.p.; 50 days) attenuates tumor xenograft growth[1].
KEA1-97 induces apoptosis in vivo through caspase activation. By disrupting the Trx-caspase-3 interaction, it relieves the inhibitory effect of thioredoxin on caspase-3, promoting programmed cell death. The compound's ability to induce apoptosis in vivo makes it a potential therapeutic agent for conditions where enhanced apoptosis is beneficial, such as cancer. The preservation of thioredoxin activity during this process suggests that the compound's effects are specific to the protein-protein interaction and do not broadly disrupt cellular redox balance. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KEA1-97. For protein-protein interaction disruptors, standard cell-free assays include fluorescence polarization, AlphaScreen, or ELISA using recombinant thioredoxin and caspase-3 proteins. The compound is incubated with the proteins, and the inhibition of interaction is measured to determine IC50 values. These assays can provide mechanistic insights into how the compound interferes with the Trx-caspase-3 interaction. Surface plasmon resonance (SPR) could also be used to measure binding affinity and kinetics.
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| Cell Assay |
No specific cell-based assay protocol is available for KEA1-97. For apoptosis induction studies, standard assays involve treatment of cancer cell lines with KEA1-97 for 24-48 hours. Following treatment, caspase activity is measured using fluorogenic substrates. Apoptosis is confirmed by Annexin V/PI staining for flow cytometry and western blot analysis of cleaved PARP and caspases. Cell viability assays (MTT or CellTiter-Glo) can also be performed to assess the compound's cytotoxic effects. Importantly, thioredoxin activity assays can confirm that the compound does not affect thioredoxin enzymatic function.
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| Animal Protocol |
No specific animal protocol is available for KEA1-97. For apoptosis-inducing compounds, standard in vivo studies use tumor xenograft models in mice. The compound is administered (route not specified) for 2-3 weeks. Tumor growth inhibition is monitored, and apoptosis markers in tumor tissues are assessed by immunohistochemistry or western blot. Pharmacodynamic studies may also be performed to confirm target engagement and pathway modulation in vivo. The compound's ability to induce apoptosis without affecting thioredoxin activity suggests a favorable safety profile in vivo.
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| ADME/Pharmacokinetics |
No pharmacokinetic data is publicly available for KEA1-97. KEA1-97 has a molecular weight of 335.16, formula C15H9Cl2FN4, and is soluble in DMSO at 90 mg/mL. It should be stored at 4°C and protected from light. Powder can be stored at 2-8°C for 2 years; in solvent at -20°C for 1 month or -80°C for 6 months. As a covalent ligand, KEA1-97 may have unique pharmacokinetic properties related to its mechanism of action, including potential for prolonged target engagement. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No toxicology data is publicly available for KEA1-97. As a covalent ligand, KEA1-97 may have off-target reactivity and requires careful toxicological evaluation. Standard preclinical safety studies would be needed for therapeutic development, including genotoxicity assessment, hERG cardiac safety evaluation, and repeated-dose toxicity studies. The compound's selectivity for the Trx-caspase-3 interaction may contribute to a manageable safety profile, but potential effects on other protein-protein interactions or covalent modification of off-target proteins would need to be assessed. The compound is for research use only.
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| References | |
| Additional Infomation |
KEA1-97 is also known as KEA197. It has a molecular weight of 335.16, formula C15H9Cl2FN4. It appears as a white to light yellow solid. Powder can be stored at 2-8°C for 2 years; in solvent at -20°C for 1 month or -80°C for 6 months. The compound is soluble in DMSO at 90 mg/mL and should be protected from light. KEA1-97 is a dichlorotriazine (DCT)-based covalent ligand that selectively disrupts the protein-protein interaction between thioredoxin and caspase-3. No clinical trial status has been identified.
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| Molecular Formula |
C15H9CL2FN4
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|---|---|
| Molecular Weight |
335.163163900375
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| Exact Mass |
334.018
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| Elemental Analysis |
C, 53.75; H, 2.71; Cl, 21.15; F, 5.67; N, 16.72
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| CAS # |
2138882-71-8
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| Related CAS # |
2138882-71-8
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| PubChem CID |
135338301
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| Appearance |
White to light yellow solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
336
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1C2=CC=C(C=C2)F)NC3=NC(=NC(=N3)Cl)Cl
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| InChi Key |
DUROVTLUQOYUPH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H9Cl2FN4/c16-13-20-14(17)22-15(21-13)19-12-7-3-10(4-8-12)9-1-5-11(18)6-2-9/h1-8H,(H,19,20,21,22)
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| Chemical Name |
4,6-dichloro-N-[4-(4-fluorophenyl)phenyl]-1,3,5-triazin-2-amine
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| Synonyms |
KEA197; KEA1 97; KEA1-97
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~298.4 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9836 mL | 14.9182 mL | 29.8365 mL | |
| 5 mM | 0.5967 mL | 2.9836 mL | 5.9673 mL | |
| 10 mM | 0.2984 mL | 1.4918 mL | 2.9836 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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