Physicochemical Properties
| CAS # | 2883447-45-6 |
| 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
| Targets | IC50: 208.8 nM (AR(T877A)), 246.6 nM (wt-AR), 268.2 nM (AR (F876L)), 490.2 nM (AR(W741L))[1] DC50: 2.84 μM (AR)[1] |
| ln Vitro | AR antagonist 4 (Compound 67-b) (0-10 μM; 6 days) suppresses the growth of LNCaP and 22RV1 cells[1]. CYP17A1 is inhibited by AR antagonist 4 at an IC50 of 2.59 μM[1]. With antagonist IC50s of 490.2, 208.8, and 268.2 nM against AR(W741L), AR(T877A), and AR (F876L), respectively, AR antagonist 4 exhibits antagonistic activities[1]. |
| ln Vivo | When testosterone propionate (TP) is given to rats, AR antagonist 4 (Compound 67-b) (20 mg/kg; po; daily for 10 days) suppresses the growth of androgen-sensitive organs (ASOs)[1]. 4 (30 mg/kg; po; daily for 4 weeks) has antitumor activity in a mouse xenograft model resistant to enzalutamide (c4-2b−ENZ)[1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: LNCaP and 22RV1 cells Tested Concentrations: 0-10 μM Incubation Duration: 6 days Experimental Results: demonstrated antiproliferative activity with IC50s of 246.6 nM and 590 nM against LNCaP and 22RV1 cells, respectively. Western Blot Analysis[1] Cell Types: LNCaP and 22RV1 cells Tested Concentrations: 0, 1, 5, 10 and 20 μM Incubation Duration: 0, 2, 4, 8, 16 and 24 h Experimental Results: Degraded androgen receptor in a dose- and time-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Castrated male Sprague−Dawley rats[1] Doses: 20 mg /kg Route of Administration: Oral administration, daily for 10 days Experimental Results: Resulted in statistically significant weight reductions in seminal vesicles (62%, p < 0.01) and ventral prostate (66%, p < 0.01) versus the testosterone propionate control. Animal/Disease Models: SPF grade male Babl/c nude male mice, enzalutamide-resistant c4-2b−ENZ xenograft model[1] Doses: 30 mg/kg Route of Administration: Oral administration, daily for 4 weeks Experimental Results: demonstrated a remarkable tumor regression with ΔT/ΔC% = −14% after 4 weeks of treatment. Animal/Disease Models: Male Sprague−Dawley rats[1] Doses: 10 mg/kg Route of Administration: Oral administration (pharmacokinetic/PK Analysis) Experimental Results: PK Parameters for AR antagonist 4 (Compound 67-b) in Male SD Ratsa[1] Compound T1/2 (h) Tmax (h) Cmax (ng/mL) AUC0-t (ng·h/mL) AR antagonist 4 2.80 2.17 2670 24 800 aCompounds were PO-dosed at 10 mg/ kg in a solution of 5% DMSO + 30% PEG400 + 65% water (0.5% MC) in male SD rats. Abbreviations |
| References |
[1]. Design, Synthesis, and Biological Evaluation of Androgen Receptor Degrading and Antagonizing Bifunctional Steroidal Analogs for the Treatment of Advanced Prostate Cancer. J Med Chem. 2022 Sep 7. |
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.) |