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.
For research use only. We do not sell to patients.
- Formula: C26H28O13S
- Molecular Weight:580.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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].
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).
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.
Chemical Information
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Molecular Weight 580.56
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Formula 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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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