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TAS-103 (also known as BMS-247615) is a potent and dual inhibitor of DNA topoisomerase I/II. It is a quinoline derivative that displays antitumor activity in murine and human tumor models. In tumor models from mice and humans, this derivative of quinoline exhibits antitumor activity. TAS-103 has an IC50 value of 5 nM and is active on CCRF-CEM cells. In individual CCRF-CEM cells, TAS-103 at 0.1 μM significantly increases levels of topo IIα FITC immunofluorescence. HeLa cell viability is inhibited by TAS-103, with an IC50 of 40 nM. At 10 μM, TAS-103 prevents the formation of signal recognition particle (SRP) complexes and causes SRP14 and SRP19 to become unstable, leading to their eventual degradation. Despite the fact that TAS-103 has been described as a strong topoisomerase II poison. However, other studies have indicated that cellular susceptibility to TAS-103 is not correlated with topoisomerase II expression.
Physicochemical Properties
| Molecular Formula | C20H192N3O2 | |
| Molecular Weight | 333.38 | |
| Exact Mass | 333.147 | |
| CAS # | 174634-08-3 | |
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| PubChem CID | 135413533 | |
| Appearance | Typically exists as solid at room temperature | |
| Density | 1.4±0.1 g/cm3 | |
| Boiling Point | 589.5±50.0 °C at 760 mmHg | |
| Flash Point | 310.3±30.1 °C | |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C | |
| Index of Refraction | 1.734 | |
| LogP | 2.71 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 5 | |
| Rotatable Bond Count | 4 | |
| Heavy Atom Count | 25 | |
| Complexity | 497 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O=C(C1=C2C3=CC=C(O)C=C3N=C1NCCN(C)C)C4=C2C=CC=C4 |
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| InChi Key | ROWSTIYZUWEOMM-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C20H19N3O2/c1-23(2)10-9-21-20-18-17(13-5-3-4-6-14(13)19(18)25)15-8-7-12(24)11-16(15)22-20/h3-8,11,24H,9-10H2,1-2H3,(H,21,22) | |
| Chemical Name | 6-[2-(dimethylamino)ethylamino]-3-hydroxyindeno[2,1-c]quinolin-7-one | |
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| 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 |
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| 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
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| Cell Assay | The RPMI-1640 medium containing 3 mM l-glutamine, 10% foetal bovine serum, 50 U/mL penicillin, and 40 μg/mL streptomycin is used to cultivate CCRF-CEM human acute lymphoblastic leukemia cells. The cells are grown at 37°C in a humidified environment with 5% CO2. The DMSO dissolves TAS-103, CPT, and DACA. After two hours, either drug is applied to cells that are exponentially growing (approximately 5 × 105). Two centrifugations (400 × g, 3 min) in cold phosphate-buffered saline are used to wash cells twice after drug exposure[1]. | |
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| References |
[1]. An investigation into the formation of N- [2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) and 6-[2-(dimethylamino)ethylamino]- 3-hydroxy-7H-indeno[2, 1-C]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II cleavable complexes in human leukaemia cells. Biochem Pharmacol. 2000 Sep 15;60(6):817-21. [2]. Cancer chemotherapy by liposomal 6-[12-(dimethylamino)ethyl]aminol-3-hydroxy-7H-indeno[2,1-clquinolin-7-one dihydrochloride (TAS-103), a novel anti-cancer agent. Biol Pharm Bull. 2002 Oct;25(10):1385-7. [3]. A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads. Mol Pharmacol. 2008 Mar;73(3):987-94. |
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| Additional Infomation | See also: Tas-103 (annotation moved to). |
Solubility Data
| Solubility (In Vitro) |
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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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9996 mL | 14.9979 mL | 29.9958 mL | |
| 5 mM | 0.5999 mL | 2.9996 mL | 5.9992 mL | |
| 10 mM | 0.3000 mL | 1.4998 mL | 2.9996 mL |