| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Ralaniten triacetate targets the N-terminal domain (NTD) of the androgen receptor (AR), a region that is essential for AR transcriptional activity and is not targeted by conventional AR antagonists that bind to the ligand-binding domain (LBD). The NTD is a novel target for AR inhibition and is involved in resistance mechanisms in castration-resistant prostate cancer (CRPC). By specifically binding to the AR NTD, ralaniten inhibits both AR activation and AR-mediated signaling. Ralaniten triacetate shows activity against full-length AR and AR variants, including AR-V7, which are associated with resistance to conventional AR antagonists.
|
|---|---|
| ln Vitro |
For the treatment of metastatic castration-resistant prostate cancer (mCRPC), ralaniten triacetate (EPI-506) is used. It targets the N-terminal domain of the androgen receptor (AR). By attaching to the N-terminal domain (NTD), a novel target on the AR, EPI-506 is a first-in-class, highly-specific small molecule that directly inhibits AR transcriptional activity by preventing the AR from interacting with transcriptional proteins[2].
In vitro, ralaniten triacetate (EPI-506) is a highly specific small molecule targeting the N-terminal domain (NTD) of the androgen receptor (AR). It is the prodrug of ralaniten and is converted to the active form in vivo. The compound's activity is assessed in cell-based assays measuring AR-mediated transcriptional activity using AR-responsive reporter gene constructs. It shows activity against full-length AR and AR variants, including AR-V7. Ralaniten triacetate is commonly used in research on metastatic castration-resistant prostate cancer (mCRPC), where resistance to androgen deprivation therapy has developed. |
| ln Vivo |
In vivo, ralaniten triacetate (EPI-506) is the first AR-NTD inhibitor to advance into human clinical trials for metastatic castration-resistant prostate cancer (mCRPC). As an orally bioavailable prodrug, it is converted to the active ralaniten in vivo. The compound has been evaluated in clinical trials for mCRPC. Its mechanism of action involves targeting the AR NTD, which is not targeted by conventional AR antagonists, offering a potential approach to overcome resistance. Further in vivo studies are needed to fully characterize its efficacy and safety.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for ralaniten triacetate typically involve assessing its interaction with the N-terminal domain (NTD) of the androgen receptor. The compound's binding affinity to the AR NTD is assessed using biophysical methods such as surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), or fluorescence polarization. Its ability to inhibit AR-mediated transcriptional activity is confirmed through functional assays using AR-responsive reporter gene constructs. The compound's activity against AR variants such as AR-V7 is also assessed.
|
| Cell Assay |
In vitro cell-based assays for ralaniten triacetate utilize AR-positive prostate cancer cell lines, including those expressing AR-V7 or other resistance-associated AR variants. Cells are treated with varying concentrations of the compound for 24-72 hours. AR-mediated transcriptional activity is evaluated using reporter gene assays with androgen response element (ARE)-luciferase constructs. Cell proliferation is assessed using MTT or CCK-8 assays. The expression of AR target genes is measured by qPCR. Standard cell culture conditions (37°C, 5% CO₂) with charcoal-stripped serum are employed.
|
| Animal Protocol |
In vivo animal studies with ralaniten triacetate typically involve administration of the compound to rodent models of prostate cancer, including castration-resistant prostate cancer (CRPC) models. The compound is administered orally at various doses. Endpoints include tumor growth measurements, assessment of AR target gene expression in tumor tissues, evaluation of apoptosis markers, and pharmacokinetic profiling. Clinical trials have evaluated ralaniten triacetate in mCRPC patients. All procedures must comply with institutional animal care and use guidelines.
|
| ADME/Pharmacokinetics |
Ralaniten triacetate is orally bioavailable. It has a molecular weight of 512.55 g/mol and a molecular formula of C₂₈H₃₂O₉. As a prodrug, it is converted to the active ralaniten (EPI-002) in vivo. The compound is typically stored under conditions recommended for research chemicals. Detailed PK parameters including half-life, Cmax, and AUC are available from preclinical and clinical study reports. The compound's oral bioavailability supports convenient dosing regimens in clinical studies.
|
| Toxicity/Toxicokinetics |
Ralaniten triacetate has been evaluated in clinical trials for metastatic castration-resistant prostate cancer (mCRPC). As an investigational drug, it has undergone toxicological evaluation in preclinical studies. Common adverse effects may include those associated with AR inhibition. Comprehensive safety data are available from clinical study reports. Ralaniten triacetate is for research use only and is not approved for human therapeutic applications. The compound is the first AR-NTD inhibitor to advance into human clinical trials.
|
| References |
|
| Additional Infomation |
Ralaniten acetate is a small molecule inhibitor with high oral bioavailability. Its active form is lanatin acetate, which contains the N-terminal domain (NTD) of the androgen receptor (AR) and possesses potential antitumor activity. After oral administration of Ralaniten acetate, lanatin specifically binds to the NTD of AR, thereby inhibiting AR activation and its mediated signaling pathways. This can inhibit the growth of AR-overexpressing tumor cells. AR is overexpressed in prostate cancer and is involved in tumor cell proliferation, survival, and chemotherapy resistance.
Ralaniten triacetate (EPI-506) (CAS#: 1637573-04-6) is a first-in-class, orally bioavailable prodrug of ralaniten, a small molecule inhibitor targeting the N-terminal domain (NTD) of the androgen receptor. It is the first AR-NTD inhibitor to advance into human clinical trials for mCRPC. Ralaniten triacetate shows activity against full-length AR and AR variants including AR-V7. This compound is not a drug and has not received regulatory approval. |
| Molecular Formula |
C27H33CLO8
|
|---|---|
| Exact Mass |
520.186
|
| CAS # |
1637573-04-6
|
| Related CAS # |
Ralaniten;1203490-23-6
|
| PubChem CID |
86278934
|
| Appearance |
Colorless to light yellow liquid
|
| LogP |
5.1
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
16
|
| Heavy Atom Count |
36
|
| Complexity |
696
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC(=O)OC[C@H](COC1=CC=C(C=C1)C(C)(C)C2=CC=C(C=C2)OC[C@@H](CCl)OC(=O)C)OC(=O)C
|
| InChi Key |
HGHVYYKTOXUQNT-CLJLJLNGSA-N
|
| InChi Code |
InChI=1S/C27H33ClO8/c1-18(29)32-16-26(36-20(3)31)17-34-24-12-8-22(9-13-24)27(4,5)21-6-10-23(11-7-21)33-15-25(14-28)35-19(2)30/h6-13,25-26H,14-17H2,1-5H3/t25-,26-/m1/s1
|
| Chemical Name |
[(2S)-2-acetyloxy-3-[4-[2-[4-[(2S)-2-acetyloxy-3-chloropropoxy]phenyl]propan-2-yl]phenoxy]propyl] acetate
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (191.94 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.80 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.80 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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.
Link: https://clinicaltrials.gov/ct2/show/NCT02606123
Conditions:Prostatic Neoplasms|Genital Neoplasms, Male|Genital Diseases, Male|Prostatic DiseasesProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
