TAK-778, a derivative of ipriflavone, has been shown to induce bone growth both in vitro and in vivo. Recently, it has been shown that TAK-778 can enhance osteoblast differentiation of human bone marrow cells via an estrogen receptor (ER)-dependent pathway. TAK-778 enhanced bone formation in OVX rats and that this effect was dependent on an ER-mediated pathway.
Physicochemical Properties
| Molecular Formula | C24H28NO7PS |
| Molecular Weight | 505.5204 |
| Exact Mass | 505.132 |
| CAS # | 180185-61-9 |
| PubChem CID | 9806177 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 3.3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 34 |
| Complexity | 764 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CCOP(=O)(CC1=CC=C(C=C1)NC(=O)[C@H]2CC3=CC4=C(C=C3C(=O)[C@@H](S2)C)OCO4)OCC |
| InChi Key | WXACSCNLLDFZHE-OYHNWAKOSA-N |
| InChi Code | InChI=1S/C24H28NO7PS/c1-4-31-33(28,32-5-2)13-16-6-8-18(9-7-16)25-24(27)22-11-17-10-20-21(30-14-29-20)12-19(17)23(26)15(3)34-22/h6-10,12,15,22H,4-5,11,13-14H2,1-3H3,(H,25,27)/t15-,22+/m0/s1 |
| Chemical Name | (6R,8S)-N-[4-(diethoxyphosphorylmethyl)phenyl]-8-methyl-9-oxo-5,6-dihydrothiepino[4,5-f][1,3]benzodioxole-6-carboxamide |
| Synonyms | TAK-778 ; TAK 778 ; TAK778 |
| 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 | It has been demonstrated that the isoflavone derivative TAK-778 stimulates bone formation in both in vitro and in vivo models. Increased mineralized nodule area was seen after 1 to 21 days of continuous treatment with TAK-778 (10 μM). Cellular alkaline phosphatase (ALP) activity is considerably stimulated by TAK-778 at doses of 1 μM or above. Confluent-stage cells' DNA content rose by TAK-778, albeit not very much. Additionally, from days 5 to 7, TAK-778 administration led to a dose-dependent increase in the amount of soluble collagen and osteocalcin secreted into the culture medium. TAK-778 increased the secretion of TGF-β and IGF-I at every stage of the treatment. 21 days devoted to culture. TAK-778 treatment of the cells increased the saturated cell density in a dose-dependent manner but did not cause ALP activity. Saturated cell density is dramatically reduced by TAK-778 at a dose of 10 μM [2]. |
| ln Vivo | Following a single topical application of TAK-778/PLGA-MC (0.2 to 5 mg/site), the radiopaque area generated in the defect increased in a dose-dependent manner. According to histological investigations, a bony bridge filled the deficiency area, and the newly produced radiopaque area, which was encircled by cuboidal osteoblasts and thick osteoid seams, matched to calcified bone encompassing the medullary cavity. No discernible variations were observed in the indices between the skulls treated with TAK-778/PLGA-MC and placebo. TAK-778/PLGA-MC particles triggered radioactive bone repair across the defect two months post-surgery [2]. When OVX mice were given TAK-778 orally, their lumbar spine bone mineral density (BMD) increased more than that of vehicle controls [3]. |
| References |
[1]. Rosa AL, et al. TAK-778 enhances osteoblast differentiation of human bone marrow cells via an estrogen-receptor-dependent pathway. J Cell Biochem. 2004 Mar 1;91(4):749-55. [2]. Notoya K, et al. Enhancement of osteogenesis in vitro and in vivo by a novel osteoblast differentiation promoting compound, TAK-778. J Pharmacol Exp Ther. 1999 Sep;290(3):1054-64. [3]. Cai M, et al. TAK-778 induces osteogenesis in ovariectomized rats via an estrogen receptor-dependent pathway. J Bone Miner Metab. 2011 Mar;29(2):168-73 |
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 | 1.9782 mL | 9.8908 mL | 19.7816 mL | |
| 5 mM | 0.3956 mL | 1.9782 mL | 3.9563 mL | |
| 10 mM | 0.1978 mL | 0.9891 mL | 1.9782 mL |