| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
ETS
TK216 directly targets the EWS-FLI1 (Ewing sarcoma breakpoint region 1/Friend leukemia virus integration 1 fusion protein) by binding to it and preventing its protein interactions. It also inhibits the binding of EWS-FLI1 to RNA helicase A. As an ETS inhibitor, TK216 disrupts the transcriptional program driven by this oncogenic fusion, leading to decreased transcription and proliferation. This makes it a promising targeted therapy for EWS-FLI1-driven cancers. |
|---|---|
| ln Vitro |
In DLBCL cell lines, TK216 (500 nM) induces apoptosis for a duration of 24-72 hours [1]. In the Ewing sarcoma A4573 cell line, TK216 (0.03, 0.06, 0.125, 0.25, 0.5 μM) inhibits growth in a dose-dependent manner [1]. DLBCL cell lines are exposed to TK216 (0.1, 0.3, and 1 μM) to induce apoptosis; the amount of cleaved caspase 3 is normalized to b-actin and displayed as fold over control [1]. TK216's half maximal inhibitory concentration (IC50) for the HL-60 AML and TMD-8 DLBCL cell lines are 0.363 μM and 0.152 μM, respectively[1]. Reduced transcription and proliferation are the results of TK216's inhibition of the EWS-FLI1 (Ewing sarcoma breakpoint region 1/Friend leukemia virus integration 1 fusion protein) protein interaction [1].
In vitro, TK216 induces apoptosis in DLBCL cell lines at 500 nM over 24–72 hours. In Ewing sarcoma A4573 cells, it inhibits growth in a dose-dependent manner at concentrations of 0.03–0.5 μM. The IC50 values for HL-60 AML and TMD-8 DLBCL cell lines are 0.363 μM and 0.152 μM, respectively. TK216 treatment leads to cleavage of caspase-3, indicating activation of the apoptotic pathway. |
| ln Vivo |
In TMD-8 xenograft models, TK216 (100 mg/kg orally; twice daily for 13 days) reduces the formation of tumors [1].
In vivo, TK216 (100 mg/kg orally; twice daily for 13 days) reduces tumor formation in TMD-8 xenograft models in NOD-SCID mice. The compound demonstrates significant tumor growth inhibition in this model, supporting its potential for treating EWS-FLI1-driven malignancies. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assays for TK216 typically involve direct binding studies to assess its interaction with the EWS-FLI1 fusion protein. Surface plasmon resonance (SPR) or similar biophysical techniques can be used to measure the binding affinity. Additionally, protein-protein interaction assays, such as co-immunoprecipitation, are employed to confirm the disruption of EWS-FLI1 interactions with RNA helicase A. These assays are crucial for validating the mechanism of action.
|
| Cell Assay |
Apoptosis Analysis[1]
Cell Types: DLBCL cell lines Tested Concentrations: 500 nM Incubation Duration: For 24, 48 or 72 hrs (hours) Experimental Results: Induced apoptosis in DLBCL cell lines. Cellular assays for TK216 are performed using various cancer cell lines, including DLBCL (e.g., TMD-8) and Ewing sarcoma (e.g., A4573) cell lines. Cells are treated with TK216 at concentrations ranging from 0.03 to 500 nM for 24–72 hours. Apoptosis is assessed by measuring cleaved caspase-3 levels, and cell proliferation is evaluated using standard viability assays. IC50 values are determined from dose-response curves to quantify the compound's potency. |
| Animal Protocol |
Animal/Disease Models: NOD-SCID (severe combined immunodeficient) mouse subcutaneously (sc) inoculated with TMD8 cells[1]
Doses: 100 mg/kg Route of Administration: PO; twice (two times) daily for 13 days Experimental Results: Resulted in tumor growth inhibition. In vivo animal studies for TK216 are conducted using NOD-SCID mice subcutaneously inoculated with TMD-8 cells. The compound is administered orally at a dose of 100 mg/kg twice daily for 13 days. Tumor growth is monitored, and the study evaluates the compound's efficacy in reducing tumor volume. These xenograft models are standard for assessing the antitumor activity of TK216 and providing preclinical proof-of-concept for its therapeutic potential. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) properties of TK216 are not fully described in the available literature. However, as an orally available compound, it is expected to have sufficient oral bioavailability. In vivo studies typically use oral administration at 100 mg/kg, indicating that the compound can achieve therapeutic concentrations via this route. Further PK studies, including plasma half-life, clearance, and volume of distribution, would be necessary to fully characterize its pharmacokinetic profile.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicity data for TK216 are not detailed in the available literature. As an investigational anticancer agent, standard toxicology assessments would be required to evaluate its safety profile. The compound is intended for research use only and is not approved for human therapeutic use. Potential toxicities related to its mechanism of action, such as effects on normal ETS transcription factor function, should be carefully evaluated in preclinical studies.
|
| References | |
| Additional Infomation |
TK216 is also known as TK-216 or ONCT-216 and is considered a first-in-class inhibitor of the EWS-FLI1 oncogenic fusion protein, exhibiting 3-4 fold greater potency than its parent compound YK-4-279 in Ewing sarcoma models. It has been investigated in clinical trials for the treatment of Ewing sarcoma. The compound is an orally active ETS inhibitor and represents a promising targeted therapy for cancers driven by ETS transcription factor fusions.
|
| Molecular Formula |
C19H15CL2NO3
|
|---|---|
| Molecular Weight |
376.2333
|
| Exact Mass |
375.04
|
| Elemental Analysis |
C, 60.66; H, 4.02; Cl, 18.84; N, 3.72; O, 12.76
|
| CAS # |
1903783-48-1
|
| Related CAS # |
1903783-48-1 (racemic); 1903783-78-7 (rotation -)
|
| PubChem CID |
121268274
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.1
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
25
|
| Complexity |
559
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC1C2=CC=C(C=C2)C(=O)CC3(C4=C(C=CC(=C4NC3=O)Cl)Cl)O
|
| InChi Key |
ZWHNLSHDLKIXOG-UHFFFAOYSA-N
|
| 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)
|
| Chemical Name |
4,7-dichloro-3-[2-(4-cyclopropylphenyl)-2-oxoethyl]-3-hydroxy-1H-indol-2-one
|
| Synonyms |
TK-216; TK216; TK 216
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 250 mg/mL (~664.5 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.53 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 20.8 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: ≥ 2.08 mg/mL (5.53 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 20.8 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: ≥ 2.08 mg/mL (5.53 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05046314 | Not yet recruiting | Biological: TK216+Vincristin | Sarcoma, Ewing | Shanghai Pharmaceuticals Holding Co., Ltd |
October 28, 2024 | Phase 2 |
| NCT02657005 | Terminated | Drug: TK216 | Sarcoma, Ewing | Oncternal Therapeutics, Inc | August 2016 | Phase 1 Phase 2 |
| NCT03752138 | Withdrawn | Drug: Group 1: TK216 Drug: Group 2: TK216 |
Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia |
M.D. Anderson Cancer Center | March 31, 2019 | Phase 1 |
|
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
