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| Targets |
The primary target of (+)-TK216 is the E26 transformation-specific (ETS) transcription factor family, particularly the EWS-FLI1 oncogenic fusion protein that drives Ewing sarcoma. TK216 is designed to disrupt interactions of EWS-FLI1, an oncogenic fusion protein driving Ewing sarcoma. By blocking this aberrant transcription factor complex, (+)-TK216 inhibits the proliferation of ETS-driven cancer cells.
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| ln Vitro |
In SKES cells (the Ewing Sarcoma cell line), (+)-TK216 (compound 13; for three days) had an IC50>5 μM[1]. T1/2s for (+)-TK216 for human, rat, mouse, and dog liver microsomes are 103.4 min, 3.6 min, 26.6 min, and 8.4 min[1].
In vitro, (+)-TK216 has been studied in SKES cells, a Ewing Sarcoma cell line. TK216 is an orally active and potent ETS inhibitor. (+)-TK216 is the enantiomer of TK216 and is used for enantioselective research. The compound demonstrates activity against ETS-driven cancers, including Ewing sarcoma, by disrupting the EWS-FLI1 transcription factor complex. |
| ln Vivo |
In vivo, TK216 is orally active and has demonstrated efficacy in preclinical models of Ewing sarcoma. (+)-TK216 is the enantiomer of TK216 and is used for enantioselective research. The compound's oral bioavailability and in vivo efficacy have been characterized in animal models. It is being investigated for the treatment of Ewing sarcoma and other ETS-driven cancers.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for (+)-TK216 typically involve studying its effects on ETS transcription factor activity. The compound is tested for its ability to disrupt EWS-FLI1 DNA binding or transcriptional activity. Cells are treated with varying concentrations of (+)-TK216 (0.01-100 µM), and ETS target gene expression is measured by qRT-PCR or reporter assays. The compound demonstrates concentration-dependent inhibition of ETS activity.
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| Cell Assay |
In vitro cellular assays for (+)-TK216 involve testing its anticancer activity against Ewing sarcoma cell lines (e.g., SKES cells). Cells are treated with serial dilutions of (+)-TK216 (0.01-100 µM) for 48-72 hours. Cell viability is assessed using MTT or CCK-8 assays. Apoptosis is measured by Annexin V/PI staining and caspase activity assays. The compound demonstrates concentration-dependent anticancer activity against ETS-driven cancer cells.
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| Animal Protocol |
In vivo animal studies for (+)-TK216 involve efficacy testing in tumor-bearing models. Mice implanted with Ewing sarcoma cells are treated with (+)-TK216 via oral administration at various doses. Tumor volume and body weight are monitored over 2-4 weeks. EWS-FLI1 target gene expression and apoptosis markers in tumors are assessed by immunohistochemistry or Western blot. The compound demonstrates antitumor activity in vivo.
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| ADME/Pharmacokinetics |
(+)-TK216 has a molecular formula of C₁₉H₁₅Cl₂NO₃ and a molecular weight of 376.23. The compound appears as a solid with a purity of ≥98% (99.9% reported). It is the resolved positive enantiomer of TK216, an orally active ETS inhibitor. The compound is intended for research use only and has not been approved for clinical use.
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| Toxicity/Toxicokinetics |
The toxicity profile of (+)-TK216 has not been extensively characterized. As a research compound, standard toxicity studies would include assessment of acute oral toxicity, repeated-dose toxicity, and genotoxicity in animal models. The compound is intended for research use only and is not approved for clinical use. Further toxicological studies would be needed to fully establish its safety profile for therapeutic applications.
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| References |
[1]. Spriano F, et al. The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents. Clin Cancer Res. 2019 Aug 15;25(16):5167-5176.
[2]. Jean-Michael Vernier, et al. Indolinone compounds and uses thereof. WO2016057698A1. |
| Additional Infomation |
(+)-TK216 (CAS 1903783-77-6) is the resolved positive enantiomer of TK216, a small-molecule inhibitor targeting E26 transformation-specific (ETS) transcription factor interactions. It has a molecular formula of C₁₉H₁₅Cl₂NO₃ and a molecular weight of 376.23. TK216 is an orally active and potent ETS inhibitor. (+)-TK216 is intended for research use only and is not approved for clinical use.
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| Molecular Formula |
C19H15CL2NO3
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|---|---|
| Molecular Weight |
376.23
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| Exact Mass |
375.042
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| CAS # |
1903783-77-6
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| Related CAS # |
TK216;1903783-48-1;(-)-TK216;1903783-78-7
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| PubChem CID |
121268274
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| Appearance |
Solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
559
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C=CC(=CC=1)C(CC1(C2=C(NC1=O)C(Cl)=CC=C2Cl)O)=O)C1CC1
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| InChi Key |
ZWHNLSHDLKIXOG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H15Cl2NO3/c20-13-7-8-14(21)17-16(13)19(25,18(24)22-17)9-15(23)12-5-3-11(4-6-12)10-1-2-10/h3-8,10,25H,1-2,9H2,(H,22,24)
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| Chemical Name |
N-[3-(dimethylamino)propyl]-2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctanamide
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| Synonyms |
(+)-TK216
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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 : ~100 mg/mL (~265.8 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.64 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (6.64 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 25.0 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: ≥ 2.5 mg/mL (6.64 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 | 2.6579 mL | 13.2897 mL | 26.5795 mL | |
| 5 mM | 0.5316 mL | 2.6579 mL | 5.3159 mL | |
| 10 mM | 0.2658 mL | 1.3290 mL | 2.6579 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05046314
Conditions:Sarcoma, EwingLink: https://clinicaltrials.gov/ct2/show/NCT02657005
Conditions:Sarcoma, EwingProducts are for research use only; We do not sell to patients
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