SARD279
Based on 1 Customer Validation
SARD279 is a HyT degrader of androgen receptor (AR). SARD279 binds to AR, recruits HSP70, mediates ubiquitin-dependent proteasomal degradation, and competitively inhibits the transactivation of AR. SARD279 exhibits antiproliferative activity in AR-dependent prostate cancer cells and castration-resistant prostate cancer cells, including those harboring the ARF876L mutation. SARD279 can be used in studies related to prostate cancer and castration-resistant prostate cancer.
(Pink: Androgen Receptor ligand (HY-117486); Blue: HyT ligand (HY-W001578); Black: linker (HY-W004896)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 96.04%
- No. CAS: 1489236-55-6
- Fòrmula: C33H41F3N4O5S
- Peso molecular:662.76
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
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HSP70 |
AR |
SARD279 (0-10000 nM; 20 h) degrades androgen receptor in VCaP prostate cancer cells with a DC50 of 1099 nM and a maximum degradation of 69% after 20 hours of treatment[1].
SARD279 (156 nM-10 μM) induces HSP70-dependent, selective degradation of androgen receptor (AR) in LNCaP human prostate cancer cells, inhibits AR-dependent gene expression with an IC50 of 156 nM, and exerts antiproliferative effects in AR-dependent and castration-resistant prostate cancer cell lines[2].
SARD279 (10 μM; 24 h) mediates Hsp70-associated degradation of androgen receptor in LNCaP human prostate tumor cells with a DC50 of 1 μM and achieves complete AR degradation at 10 μM[3].
SARD279 (500 nM-10 μM; 24 h) induces proteasome-dependent degradation of the androgen receptor in LNCaP human prostate tumor cells with a DC50 of 1 μM, and this activity is enhanced by Hsp90 inhibition[5].
SARD279 antagonizes androgen receptor target gene expression in AR-overexpressing LNCaP-AR human prostate tumor cells without exhibiting agonist activity[5].
SARD279 (3 μM; 9 days) specifically suppresses proliferation of AR-dependent LNCaP human prostate tumor cells, with no effect on AR-independent cell lines[5].
SARD279 (0.01-10 μM; 7 days) retains dose-dependent antiproliferative activity in LNCaP human prostate tumor cells in the presence of 1 nM R1881, overcoming androgen-mediated resistance to MDV3100[5].
SARD279 (0.01-3 μM; 7 days) exerts dose-dependent antiproliferative effects in MDV3100-resistant LNCaP/ARF876L human prostate tumor cells, overcoming F876L mutation-mediated resistance[5].
Pre-fused SARD279 (0.03-0.5 μM; 24 h) (with HSP70, delivered via 80-O14B LNPs) potently degrades androgen receptor in LNCaP cells with a DC50 of ~0.06 μM, while free SARD279 (0.12-0.5 μM; 24 h) shows no AR degradation at concentrations up to 0.5 μM[4].
SARD279 binds directly to the androgen receptor with reduced affinity (37-fold lower than RU59063)[5].
SARD279 blocks androgen receptor transactivation in 293 cells with an IC50 of 156 nM[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:VCaP prostate cancer cells
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Concentration:0-10000 nM
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Incubation Time:20 h
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Result:Induced AR degradation in VCaP cells, achieving a maximum degradation (Dmax) of 69% and a half-maximal degradation concentration (DC50) of 1099 nM.
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Cell Line:LNCaP cells
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Concentration:0.03-0.5 μM (pre-fused SARD279); 0.12-0.5 μM (free SARD279)
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Incubation Time:24 h (pre-fused SARD279); 24 h (free SARD279)
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Result:Showed no AR degradation in LNCaP cells at concentrations from 0.125 to 0.5 μM (free SARD279).
Achieved more than 80% AR degradation at 0.5 μM (pre-fused SARD279 with HSP70 delivered via LNPs).
Exhibited concentration-dependent degradation with a DC50 of approximately 0.06 μM (pre-fused SARD279), which is about 16 times lower than the DC50 of free SARD279.
Showed no increase in AR degradation efficiency when LNPs were added alone.
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Cell Line:LNCaP human prostate tumor cells
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Concentration:500 nM, 1 μM, 2.5 μM, 5 μM, 10 μM
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Incubation Time:24 h
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Result:Reduced AR protein levels in a concentration-dependent manner, with a DC50 of 1 μM.
Blocked SARD279-induced AR degradation by co-incubation with the competitive AR agonist RU59063.
Prevented SARD279-induced AR degradation by pretreatment/co-treatment with the proteasome-specific inhibitor epoxomicin.
Enhanced AR degradation at sub-DC50 concentrations when co-incubated with the Hsp90 inhibitor geldanamycin (at concentrations that did not affect AR levels alone).
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Cell Line:LNCaP human prostate tumor cells; HEK293T cells; PC3 human prostate cancer cells
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Concentration:3 μM
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Incubation Time:9 days
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Result:Suppressed LNCaP cell proliferation with similar efficacy to MDV3100 within 2 days.
Did not affect proliferation of AR-independent HEK293T and PC3 human prostate cancer cell lines.
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Cell Line:LNCaP human prostate tumor cells
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Concentration:0.01 μM, 0.1 μM, 1 μM, 10 μM
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Incubation Time:7 days
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Result:Exhibited dose-dependent antiproliferative activity in LNCaP cells treated with 1 nM R1881.
Showed retained antiproliferative efficacy while MDV3100 lost antiproliferative efficacy under these conditions.
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Cell Line:LNCaP/AR-F876L (MDV3100-resistant, AR-F876L mutant) human prostate tumor cells
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Concentration:0.01 μM, 0.3 μM, 1 μM, 3 μM
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Incubation Time:7 days
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Result:Exhibited dose-dependent antiproliferative activity in LNCaP/AR-F876L cells.
Showed antiproliferative effects while MDV3100 induced proliferation in these cells.
Chemical Information
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No. CAS 1489236-55-6
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Appearance Solid
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Peso molecular 662.76
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Fòrmula C33H41F3N4O5S
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Color White to off-white
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SMILES
O=C(OCCOCCNC(CCCN(C1(C)C)C(N(C(C=C2)=CC(C(F)(F)F)=C2C#N)C1=O)=S)=O)CC3(C[C@H](C4)C5)C[C@H]5C[C@H]4C3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 100 mg/mL (150.88 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (7.54 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (7.54 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Salami J, et al. Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance. Communications biology. 2018;1:100. [Content Brief]
[2]. Collins I, et al. Chemical approaches to targeted protein degradation through modulation of the ubiquitin-proteasome pathway. The Biochemical journal. 2017 Mar 15;474(7):1127-1147. [Content Brief]
[3]. Xie S, et al. Small-Molecule Hydrophobic Tagging: A Promising Strategy of Druglike Technology for Targeted Protein Degradation. Journal of medicinal chemistry. 2023 Aug 24;66(16):10917-10933. [Content Brief]
[4]. Chen J, et al. Enhanced protein degradation by intracellular delivery of pre-fused PROTACs using lipid-like nanoparticles. Journal of controlled release : official journal of the Controlled Release Society. 2021 Feb 10;330:1244-1249. [Content Brief]
[5]. Gustafson JL, et al. Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging. Angewandte Chemie (International ed. in English). 2015 Aug 10;54(33):9659-62. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.5088 mL | 7.5442 mL | 15.0884 mL | 37.7210 mL |
| 5 mM | 0.3018 mL | 1.5088 mL | 3.0177 mL | 7.5442 mL | |
| 10 mM | 0.1509 mL | 0.7544 mL | 1.5088 mL | 3.7721 mL | |
| 15 mM | 0.1006 mL | 0.5029 mL | 1.0059 mL | 2.5147 mL | |
| 20 mM | 0.0754 mL | 0.3772 mL | 0.7544 mL | 1.8861 mL | |
| 25 mM | 0.0604 mL | 0.3018 mL | 0.6035 mL | 1.5088 mL | |
| 30 mM | 0.0503 mL | 0.2515 mL | 0.5029 mL | 1.2574 mL | |
| 40 mM | 0.0377 mL | 0.1886 mL | 0.3772 mL | 0.9430 mL | |
| 50 mM | 0.0302 mL | 0.1509 mL | 0.3018 mL | 0.7544 mL | |
| 60 mM | 0.0251 mL | 0.1257 mL | 0.2515 mL | 0.6287 mL | |
| 80 mM | 0.0189 mL | 0.0943 mL | 0.1886 mL | 0.4715 mL | |
| 100 mM | 0.0151 mL | 0.0754 mL | 0.1509 mL | 0.3772 mL |
SARD279 Related Classifications
HY-164807 Related Classifications
Powered by Bioz
- SARD279
- 1489236-55-6
- SARD 279
- SARD-279
- HyT
- Androgen Receptor
- HSP
- 293 cells
- castration-resistant prostate cancer
- HSP70
- VCaP prostate cancer cells
- LNCaP-AR human prostate tumor cells
- ubiquitin-dependent proteasomal degradation
- glucocorticoid receptor
- LNCaP human prostate cancer cells
- F876L AR mutation
- androgen receptor
- Inhibitor
- inhibitor
- inhibit