| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
Androgen receptor N-terminal domain (AR NTD), a region essential for AR transcriptional activity that is not targeted by conventional AR ligands. By binding the NTD, EPI-7170 inhibits AR-mediated gene expression regardless of C-terminal ligand-binding domain mutations.
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| ln Vitro |
When paired with EPI-7170 lower (EC = 50), EPI-7170 (0-12 μM, 24 or 48 hours) reduces the growth of VCaP-ENZR and C4-2B-ENZR cells and amplifies the action of enzalutamide[1]. In ENZR cells expressing androgen receptor splice variation 7 (AR-V7), EPI-7170 (0–20 μM, 24 or 48 hours) works in concert with enzalutamide to suppress androgen receptor (AR) transcriptional activity [1]. EPI-7170 (3.5 μM, 48 h) reduces the expression levels of CDK4, cyclin D1, and cyclin A2 proteins and increases the G1 phase while decreasing the S phase [1].
EPI-7170 inhibits the transcriptional activity of FL-AR and AR-Vs in reporter assays. It has shown antitumor activity in enzalutamide-resistant castration-resistant prostate cancer (CRPC) cell lines, where it reduces cell viability and suppresses AR-driven gene expression at sub-micromolar concentrations. |
| ln Vivo |
In male NOD/SCID mice, EPI-7170 (orally, 30 mg/kg, daily, for 31 days) has some anti-tumor activity and can be used with enzalutamide [1].
EPI-7170 exhibits antitumor effects against enzalutamide-resistant CRPC in preclinical xenograft models. Oral administration leads to significant tumor growth inhibition and suppression of AR target genes (PSA, TMPRSS2) without significant body weight loss or overt toxicity. |
| Enzyme Assay |
Recombinant AR NTD protein (0.1-1 microM) is incubated with EPI-7170 (0.001-100 microM) in binding buffer (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 0.05% NP-40) for 1-2 hours at 4degC. Binding affinity is determined by surface plasmon resonance (SPR) or fluorescence polarization using labeled AR NTD peptides.
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| Cell Assay |
Cell cycle analysis [1]
Cell Types: C4-2B-ENZR Cell Tested Concentrations: 3.5 μM Incubation Duration: 48 h Experimental Results: Experimental Results: increased G1 phase, diminished S phase, diminished expression levels of CDK4, cyclin D1 and cyclin A2 protein. AR-positive prostate cancer cells (e.g., 22Rv1, VCaP, LNCaP) are treated with EPI-7170 (0.01-10 microM) for 48-72 hours. Cell viability is measured by CellTiter-Glo or MTT. AR transcriptional activity is assessed by qPCR (PSA, TMPRSS2) and Western blot for AR target proteins. |
| Animal Protocol |
Animal/Disease Models: 6-8 week old male NOD/SCID (severe combined immunodeficient) mouse infected with VCaP-ENZR cells [1]
Doses: 30 mg/kg Route of Administration: Oral; Route of Administration: Oral. Routine; 31-day Experimental Results: Significant reduction in tumor volume and reduction in FL-AR and AR-V7 levels in harvested xenografts. Male athymic nude mice bearing enzalutamide-resistant 22Rv1 xenografts (150-200 mm3) receive EPI-7170 (e.g., 25-100 mg/kg, oral gavage, once daily) for 28-42 days. Tumor volume is measured bi-weekly, and tumors are excised for immunohistochemistry and Western blot analysis. |
| ADME/Pharmacokinetics |
EPI-7170 is orally bioavailable, with Cmax achieved at 1-4 hours post-dose. In rodents, the terminal half-life is approximately 4-8 hours. Plasma protein binding is predicted to be high (>95%) due to its lipophilic nature.
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| Toxicity/Toxicokinetics |
No formal toxicity data; however, in animal efficacy studies, EPI-7170 is well-tolerated at doses up to 100 mg/kg/day, with no observed body weight loss, hepatotoxicity, or nephrotoxicity. The compound has a favorable selectivity profile.
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| References | |
| Additional Infomation |
EPI-7170 is an investigational compound for research use only, not FDA-approved. It is designed to overcome resistance to enzalutamide and other AR antagonists that target the AR ligand-binding domain. EPI-7170 is a valuable tool for studying AR NTD biology and CRPC.
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| Molecular Formula |
C22H28CL3NO6S
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|---|---|
| Molecular Weight |
540.88
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| Exact Mass |
539.07
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| CAS # |
2139288-26-7
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| Related CAS # |
2139288-26-7;2139289-01-1 (racemic);
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| PubChem CID |
132007583
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
33
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| Complexity |
672
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CS(NC[C@@H](O)COC1=CC=C(C(C2=CC(Cl)=C(OC[C@H](O)CCl)C(Cl)=C2)(C)C)C=C1)(=O)=O
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| InChi Key |
DCXVYXPVNSMWPG-IAGOWNOFSA-N
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| InChi Code |
InChI=1S/C22H28Cl3NO6S/c1-22(2,15-8-19(24)21(20(25)9-15)32-12-16(27)10-23)14-4-6-18(7-5-14)31-13-17(28)11-26-33(3,29)30/h4-9,16-17,26-28H,10-13H2,1-3H3/t16-,17-/m1/s1
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| Chemical Name |
N-[(2R)-3-[4-[2-[3,5-dichloro-4-[(2S)-3-chloro-2-hydroxypropoxy]phenyl]propan-2-yl]phenoxy]-2-hydroxypropyl]methanesulfonamide
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8488 mL | 9.2442 mL | 18.4884 mL | |
| 5 mM | 0.3698 mL | 1.8488 mL | 3.6977 mL | |
| 10 mM | 0.1849 mL | 0.9244 mL | 1.8488 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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