PeS-9
PeS-9 is an Androgen Receptor (AR) degrader that induces androgen receptor degradation PeS-9 induces mitochondrial and ER stress by promoting cytotoxic ROS production, leading to the release of mitochondrial cytochrome C and AIF. PeS-9 subsequently activates caspases-9 and -3, causing DNA fragmentation and apoptotic cell death. PeS-9 has anticancer activity against prostate cancer and exerts in vivo antitumor and antimetastatic activity with minor side effects. PeS-9 can be used for the study of targeting monotherapy against GLUT-1-overexpressing tumors.
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- 分子式: C26H28O13S
- 分子量:580.56
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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生物活性
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化学情報
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
PeS-9 is an Androgen Receptor (AR) degrader that induces androgen receptor degradation PeS-9 induces mitochondrial and ER stress by promoting cytotoxic ROS production, leading to the release of mitochondrial cytochrome C and AIF. PeS-9 subsequently activates caspases-9 and -3, causing DNA fragmentation and apoptotic cell death. PeS-9 has anticancer activity against prostate cancer and exerts in vivo antitumor and antimetastatic activity with minor side effects. PeS-9 can be used for the study of targeting monotherapy against GLUT-1-overexpressing tumors[1].
体外実験
PeS-9 (48 h) shows cytotoxicity in cancer cells with IC50s of 0.49 μM (DU145), and 0.58 μM (LNCaP), while has low cytotoxicity for noncancer cells with IC50s of 3.41 μM (PNT2), 3.53 μM (MRC-9), 11.7 μM (HUVEC) and 7.51 μM (HEK)[1].
PeS-9 (0-2.5 μM, 4-48 h) downregulates the AR signaling pathway, produces ROS, and damages DNA in 22Rv1 cells[1].
PeS-9 (48 h) synergizes with antiandrogen Enzalutamide (HY-70002) and PARP inhibitor Olaparib (HY-10162) with CI ＜ 0.75 in 22Rv1 cells[1].
PeS-9 (0-1 μM, 1 h) activates the MAPK signaling pathways by increasing the level of stress kinases p-p38, p-JNK, and p-ERK in 22Rv1 cells, which can be antagonized by the tested MAPK inhibitor[1].
PeS-9 (0-2.5 μM, 1-48 h) induces apoptosis in 22Rv1 cells through mitochondrial targeting and cytotoxic ROS induction[1].
PeS-9 (0-2.5 μM, 1-48 h) causes increased cytosolic Ca2+ levels, expansion of the endoplasmic reticulum (ER), altered mitochondrial membrane permeability, and DNA damage, as quantified by an elevated sub-G1 cell population[1].
PeS-9 (0.5-4 μM, 24 h) inhibits the uptake of glucose in 22Rv1 cells, and this effect can be inhibited by GLUT-1 inhibitor Phloretin (HY-N0142)[1].
PeS-9 (0.1-10 μM, every 5 days over 20 days) reduces the survival fractions of tumoroids upon dose-dependently[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:22Rv1 cells
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Concentration:1, 2 μM
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Incubation Time:48 h
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Result:Downregulated AR-FL, AR-V7, PSA, IGF-1 proteins dose-dependently.
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Cell Line:22Rv1 cells
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Concentration:0, 0.5, 1, 2 μM
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Incubation Time:48 h
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Result:Inhibited the transcription of TMPRSS2, FKBP5 and PSA genes dose-dependently.
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Cell Line:22Rv1 cells
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Concentration:1.25, 2.5 μM
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Incubation Time:4, 24 h,48h
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Result:Induced DNA double-strand breaks (DSBs), as demonstrated by γH2AX/53BP1 foci formation Triggered primary DNA damage within 4 hours of treatment, reached peak damage levels at 24 hours, and showed signs of DNA repair activation by 48 hours.
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Cell Line:22Rv1 cells
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Concentration:0.5-4 μM
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Incubation Time:48 h
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Result:Increased Bax/Bcl-2 ratio (0.5, 1, 2, 4, 8 μM).
Downregulated of antiapoptotic surviving-survivin (1, 2 μM).
Released cytotoxic mitochondrial proteins such as apoptosis-inducing factor (AIF) and cytochrome C to cellular cytoplasm (2, 4 μM).
Increased the level of caspase-9, caspase-3 and PRAP (2, 4 μM).
体内実験
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD/SCID gamma (NSG) 8-12 weeks mice bearing subcutaneously xenotransplanted human prostate cancer 22Rv1 cells[1].
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Dosage:27.9 mg/kg
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Administration:Daily i.p. administration for 15 days
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Result:Reduced 40.0% tumor volume compared with the control group (1069.5 mm3 vs. 646.6 mm3).
Reduced 4.4-fold lung micrometastases.
Showed no significant difference on the weights of the body, heart, lungs, liver, and kidney.
Enlarged spleen that indicate an immunostimulatory effect of the treatment.
Showed no significant difference on the white and red blood cells, platelets, hemoglobin content, and hematocrit.
Revealed no signs of tissue damage, inflammation or granuloma.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Cell Cytotoxicity Assay
- Mammalian live/dead viability and cytotoxicity staining
- ROS/oxidative-stress fluorescent staining
- Research Protocol for Endocrine Diseases
- Apoptosis Solutions
- Cell Viability Determination by MTT Colorimetric Assay
化学情報
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分子量 580.56
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分子式 C26H28O13S
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SMILES
COC1=C(CSC[C@H]2O[C@H]([C@@H]([C@H]([C@@H]2OC(C)=O)OC(C)=O)OC(C)=O)OC(C)=O)C(C3=C(C=CC=C3O)C1=O)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
PeS-9 関連分類
HY-174377 関連分類
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