Physicochemical Properties
| CAS # | 2787593-12-6 |
| Appearance | Typically exists as solid at room temperature |
| 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 | In comparison to Triptolide, Antitumor agent-76 (Compound TP-P1) exhibits superior aqueous solubility with a 6.13 mg/mL water solubility and high stability in aqueous solution[1]. In rat plasma, antitumor agent-76 (50 μg/mL) can be quickly and totally transformed into triptolide in 30 minutes, and in human plasma, in 45 minutes. The conversion rate is not significantly affected by Antitumor Agent-76 concentration[1]. AML cells are susceptible to antiproliferative actions by antitumor agent-76 (30-120 nM; 24 h), whereas normal cells are not cytotoxically affected[1]. |
| ln Vivo | In mice THP-1 and MV-4-11 xenograft models, antitumor agent-76 (Compound TP-P1) (0-1.2 mg/kg; ip; daily for 28 days) reduces tumor cell growth, proliferation, and promotes tumor cell apoptosis[1]. In mouse MV-4-11 xenograft models, antitumor agent-76 (100, 300 μg/kg/day; ir; 11 days) dose-dependently reduces tumor growth[1]. The high esterase presence in liver makes antitumor agent-76 hydrolyzable in liver microsomes. T1/2=8.64 minutes is the short half-life, and the clearance rate is high[1]. Pharmacokinetic analysis of triptolide and antitumor agent-76 (Compound TP-P1) in Sprague Dawley rats[1]. AUC(0-t) (h ng/ml) Tmax (h) VZ /F (L/kg) CLZ/F (L/h/kg) Cmax (μg/L) Antitumor agent-76 1.6 60.46 0.50 37831.99 24563.25 23.53 The values displayed are the averages from three separate animals. Oral gavage was the method used to provide the dosed po (oral administration). |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: THP-1 and MV-4-11 cells Tested Concentrations: 30, 60, or 120 nM Incubation Duration: 24 h Experimental Results: demonstrated antiproliferative activities with IC50s of 14.79±0.42 nM and 45.97±0.13 nM against THP-1 and MV-4-11 cells, respectively. |
| Animal Protocol |
Animal/Disease Models: Male BALB/c Nude mice, THP-1 xenograft and MV-4-11 xenograft[1] Doses: 0.1, 0.3, 0.6, 1.2 mg/kg for THP-1 xenograft, 25 , 50, 100 μg/kg for MV-4-11 xenograft Route of Administration: intraperitoneal (ip)administration, daily for 28 days Experimental Results: Dramatically and dose-dependently inhibited the tumor growth in THP-1 xenografts, with an excellent tumor growth inhibitory rate (TGI) of 93.87% at the dosage of 100 μg/kg. Inhibited cell proliferation and induced cell apoptosis in tumor tissues. Also demonstrated excellent antitumor activity in MV-4-11 xenograft models (25 μg/kg with a TGI of 54.3%), and the tumors achieved complete regression on day 12 at the dosage of 100 μg/kg. Animal/Disease Models: Sprague Dawley rats[1] Doses: 1.6 mg/kg Route of Administration: Oral administration (pharmacokinetic/PK Analysis) Experimental Results: demonstrated an acceptable pharmacokinetic/PK property. |
| References | [1]. Kang D, et al. Discovery of a novel water-soluble, rapid-release triptolide prodrug with improved drug-like properties and high efficacy in human acute myeloid leukemia. Eur J Med Chem. 2022 Sep 5;243:114694. |
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.) |