TAK-024 is a novel and potent platelet inhibitor with IC50s of 31, 79 and 51 nM in human, monkey and guinea pig, respectively. It showed a potent inhibitory effect on platelet aggregation and good dissociation between the efficacy and the bleeding side effect. Intravenous infusion of compound TAK-024 at 1.6 microg/mL/min completely prevented arterial thrombus formation induced by endothelial injury in guinea pigs. The dose of TAK-024 that prolonged the bleeding time to three times the control value was 5.8 microg/mL/min. These results suggest that compound TAK-024 might be useful in the clinical treatment of thrombotic diseases, and TAK-024 was selected as a candidate for the clinical trials.
Physicochemical Properties
| Molecular Formula | C27H34N10O6 |
| Molecular Weight | 594.62226 |
| Exact Mass | 594.266 |
| CAS # | 186971-69-7 |
| PubChem CID | 9830049 |
| Appearance | Typically exists as solid at room temperature |
| LogP | -1.7 |
| Hydrogen Bond Donor Count | 7 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 43 |
| Complexity | 1070 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C1CN([C@H](C(=O)N1CC(=O)O)CCCNC(=O)C2=CC=C(C=C2)N=C(N)N)C(=O)CNC(=O)C3=CC=C(C=C3)N=C(N)N |
| InChi Key | YKSPQSYSZRGOSU-FQEVSTJZSA-N |
| InChi Code | InChI=1S/C27H34N10O6/c28-26(29)34-18-7-3-16(4-8-18)23(41)32-11-1-2-20-25(43)36(15-22(39)40)12-13-37(20)21(38)14-33-24(42)17-5-9-19(10-6-17)35-27(30)31/h3-10,20H,1-2,11-15H2,(H,32,41)(H,33,42)(H,39,40)(H4,28,29,34)(H4,30,31,35)/t20-/m0/s1 |
| Chemical Name | 2-[(3S)-4-[2-[[4-(diaminomethylideneamino)benzoyl]amino]acetyl]-3-[3-[[4-(diaminomethylideneamino)benzoyl]amino]propyl]-2-oxopiperazin-1-yl]acetic acid |
| Synonyms | TAK-024; TAK 024; TAK024 |
| 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
| ln Vitro | The platelet inhibitor TAK-024 has IC50 values of 31, 79, and 51 nM in guinea pigs, humans, and monkeys, respectively. TAK-024's IC50 value in heparinized blood samples was found to be 230 nM in preliminary investigations. This value is 4.5 times lower than the IC50 in citrated physiological blood samples. TAK-024 has an ID50 value of 0.18 μg/kg/min on isolated ADP-induced guinea pig platelet aggregation and a dissociation ratio of 32 [1]. |
| ln Vivo | In guinea pigs, endothelial injury-induced arterial thrombosis was entirely avoided by administering TAK-024 (compound 12c) intravenously at a rate of 1.6 μg/mL/min. Results indicated that TAK-024, with an ID50 value of 0.73 μg/kg/min, had an inhibitory impact on carotid artery thrombosis in guinea pigs caused by balloon damage. After 240 minutes, over 40% inhibition was still evident with a single intravenous dose of TAK-024 at 100 μg/kg, which produced nearly total inhibition in 120 minutes. Platelet aggregation can be dose-dependently inhibited with a single intravenous injection of 30 to 100 μg/kg TAK-024 [1]. |
| References | J Med Chem.2001 Jul 19;44(15):2438-50. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 | 1.6817 mL | 8.4087 mL | 16.8175 mL | |
| 5 mM | 0.3363 mL | 1.6817 mL | 3.3635 mL | |
| 10 mM | 0.1682 mL | 0.8409 mL | 1.6817 mL |