Physicochemical Properties
| 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 |
| 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) |
Biological Activity
| Targets | ETS |
| 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]. |
| ln Vivo | In TMD-8 xenograft models, TK216 (100 mg/kg orally; twice daily for 13 days) reduces the formation of tumors [1]. |
| 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. |
| 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. |
| References |
[1]. The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents. Clin Cancer Res. 2019 Aug 15;25(16):5167-5176. [2]. Uses of indolinone compounds. US10159660B2. |
Solubility Data
| 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. 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. 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 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 | 2.6579 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 |