| ln Vitro |
AR antagonist 17 (Compound C13) (72–120 hours) exhibited excellent AR antagonistic activity and antiproliferative effects against AR-positive PCa cell lines (LNCaP (IC50 = 1.02 μM), C4−2B (IC50 = 3.86 μM), 22RV1 (IC50 = 8.45 μM), and VCaP (IC50 = 5.72 μM)), while showing low toxicity to normal cell lines 3T3 and Ges-1 (IC50 > 20 μM) [1]. AR antagonist 17 (0.2–2 μM, 2 weeks) completely inhibited the clonal proliferation of LNCaP cells [1]. AR antagonist 17 (0.02–2 μM, 48 h) dose-dependently inhibited dihydrotestosterone (DHT)-induced prostate-specific antigen (PSA) transcription levels and significantly suppressed the mRNA levels of two AR-regulated downstream genes, FKBP5 and TMPRSS2, in LNCaP cells [1]. AR antagonist 17 (0.1–10 μM, 24 h) dose-dependently inhibited endogenous PSA protein expression but had no significant effect on AR protein expression in LNCaP cells [1]. AR antagonist 17 (0.1–10 μM, 4 h) dose-dependently inhibited DHT-induced AR dimerization and completely blocked the process in 293T cells at a concentration of 10 μM [1]. AR antagonist 17 (10 μM, 8 hours) can keep AR mainly in the cytoplasm and effectively prevent AR nuclear translocation in LNCaP cells[1]. AR antagonist 17 (24 hours) showed excellent antagonistic activity against clinically common AR resistance mutations (ARF877L/T878A (IC50 = 0.35 μM), ARW742C (IC50 = 0.50 μM), ARF877L (IC50 = 0.070 μM))[1]. AR antagonist 17 (2 μM, 48 h) significantly inhibited eight clinically relevant PCa relapse markers in LNCaP cells: KLK3 (encoding PSA), TMPRSS2, KLK2, NKX3.1, SLC45A3, PMEPA1, TARP and TM4SF1, as well as cancer-related processes, apoptosis regulators STK39, HERC3 and GRIN3A[1]. AR antagonist 17 (2 μM, 48 h) significantly inhibited the expression of pan-cancer-related biomarkers associated with DNA biosynthesis and repair in LNCaP cells, including EXO1, CYP11A1, PGC, RRM2 and FAM111B[1].
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| ln Vivo |
AR antagonist 17 (5 mg/kg, orally, 2–8 hours) has lower blood-brain barrier permeability in SD mice, which may result in better safety and fewer central nervous system-related side effects [1]. AR antagonist 17 (40 mg/kg, orally, twice daily for 32 days) showed significant growth inhibition in CB17 SCID mice throughout the treatment period and did not cause significant weight loss, tumor attenuation, or other toxicity outbreaks during the experiment [1].
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: LNCaP cells Tested Concentrations: 0.2 μM, 2 μM Incubation Duration: 2 week Experimental Results: Inhibited clonal proliferation at a concentration of 2.0 μM, showing better inhibitory activity against clonal proliferation than Enz 0.2 μM. Western Blot Analysis[1] Cell Types: LNCaP cells Tested Concentrations: 0.1 Μm, 1 μM, 10 μM Incubation Duration: 24 h Experimental Results: Inhibited endogenous PSA protein expression but had no significant effect on AR protein expression in LNCaP cells. RT-PCR[1] Cell Types: LNCaP cells Tested Concentrations: 0.02 μM, 0.2 μM, 2 μM Incubation Duration: 48 h Experimental Results: Suppressed the DHT-induced transcriptional levels of prostate-specific antigen (PSA), and remarkably suppressed mRNA levels of two AR-regulated downstream genes, FKBP5 and TMPRSS2. Western Blot Analysis[1] Cell Types: LNCaP cells Tested Concentrations: 10 μM Incubation Duration: 8 h Experimental Results: Effectively inhibited DHT-induced AR nuclear translocation; AR mainly remains in the cytoplasm. RT-PCR[1] Cell Types: LNCaP cells Tested Concentrations: 2 μM Incubation Duration: 48 h Experimental Results: Significantly suppressed eight clinically relevant PCa recurrence markers: KLK3 (encoding PSA), TMPRSS2, KLK2, NKX3.1, SLC45A3, PMEPA1, TARP, and TM4SF1, alongside cancer-related processes, apoptosis regulators STK39, HERC3, and GRIN3A in LNCaP cells. Significantly inhibited the expression of the pan-cancer-related biomarkers for DNA biosynthesis and repair, including EXO1, CYP11A1, PGC, RRM2, and FAM111B in LNCaP cells. |
| Animal Protocol |
Animal/Disease Models: SD Rats[1]
Doses: 5.0 mg/kg Route of Administration: Oral gavage Experimental Results: Had low blood-brain barrier permeability in SD Rats. Animal/Disease Models: LNCaP cells (1 × 107) were implanted subcutaneously into the right flanks of the 6-week-old male CB17 SCID mice[1]. Doses: 40 mg/kg Route of Administration: Oral gavage, twice daily for 32 days Experimental Results: The tumor growth inhibition (TGI) of AR antagonist 17 was 123.41%. Exhibited good tolerance and did not induce significant body weight loss or other signs of toxicity during the experiment. |
| References |
| CAS # |
3064715-04-1
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| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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