ZNU-IMB-Z15
Based on 1 Customer Validation
ZNU-IMB-Z15 is a bifunctional, selective androgen receptor (AR) antagonist and degrader. ZNU-IMB-Z15 directly binds to the ligand-binding domain (LBD) and transactivation function 1 (AF1) of AR, with an IC50 of 63.3 nM for competitive binding to AR LBD and a KD of 0.93 μM for AR AF1. ZNU-IMB-Z15 inhibits AR transcriptional activity and promotes the degradation of AR and ARV7 via the ubiquitin-proteasome pathway. ZNU-IMB-Z15 can be used for the research of castration-resistant prostate cancer.
For research use only. We do not sell to patients.
- Purity: 99.03%
- CAS No.: 920915-26-0
- Formula: C20H17N3O3S2
- Molecular Weight:411.50
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Storage: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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
AR 63.3 nM (IC50, AR LBD competitive binding) |
AR 21 μM (Kd, AR LBD) |
AR 0.93 μM (Kd, AR AF1) |
AR 1.05 μM (DC50) |
AR 1.16 μM (DC50) |
AR-V7 2.24 μM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| VCaP | IC50 |
1.37 μM
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Antiproliferative activity against human VCaP prostate cancer cells assessed via MTT cell proliferation assay after 72 hr incubation.
Antiproliferative activity against human VCaP prostate cancer cells assessed via MTT cell proliferation assay after 72 hr incubation.
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36656639 |
| 22Rv1 | IC50 |
3.63 μM
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Antiproliferative activity against human 22Rv1 prostate cancer cells assessed via MTT cell proliferation assay after 72 hr incubation.
Antiproliferative activity against human 22Rv1 prostate cancer cells assessed via MTT cell proliferation assay after 72 hr incubation.
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36656639 |
In Vitro
ZNU-IMB-Z15 (compound Z15) (5 nM DHT; 24 h) inhibits DHT-induced AR transcriptional activity in wt-AR-transfected PC-3 cells and LNCaP cells in a dose-dependent manner, with an IC50 of approximately 0.22 μM for AR transcriptional inhibition in LNCaP cells. Meanwhile, ZNU-IMB-Z15 inhibits the transcriptional activity of AR-overexpressing VCaP cells, AR/ARV7-positive 22Rv1 cells, as well as AR T877A and AR F876L mutants[1].
ZNU-IMB-Z15 exhibits an IC50 of 0.41 μM for inhibiting AR transcriptional activity, while its IC50 values for GR and ER are both greater than 20 μM, and the IC50 for PR is 9.29 μM, demonstrating selectivity for AR[1].
ZNU-IMB-Z15 binds directly to AR LBD, with an IC50 of 63.3 nM in the [3H]DHT competitive binding assay and a KD of 21.0 μM in the BLI assay; ZNU-IMB-Z15 also binds directly to AR AF1, with a KD of 0.93 μM measured by SPR[1].
ZNU-IMB-Z15 (72 h) inhibits the proliferation of AR-positive CRPC cells, with IC50 values of 1.37 μM and 3.63 μM in VCaP and 22Rv1 cells, respectively, while exerts weak inhibitory effects on the proliferation of AR-negative PC-3 and DU145 cells[1].
ZNU-IMB-Z15 (1 μM; 12-14 days) significantly reduces colony formation of 22Rv1 cells, but does not affect colony formation of AR-negative PC-3 cells[1].
ZNU-IMB-Z15 (7 days) inhibits the proliferation of organoids derived from prostate cancer tissues[1].
ZNU-IMB-Z15 (0.2-5 μM; 24 h) reduces AR protein levels in LNCaP, 22Rv1 and VCaP cells, and decreases the expression of AR downstream targets PSA, PMEPA1 and TMPRSS2; the DC50 value for AR is 1.05 μM in LNCaP cells, while the DC50 values for AR and ARV7 are 1.16 μM and 2.24 μM, respectively, in 22Rv1 cells[1].
ZNU-IMB-Z15 (5 μM; 5 nM DHT; 4 h) inhibits DHT-induced AR nuclear translocation in LNCaP cells[1].
ZNU-IMB-Z15 (5 μM) accelerates the degradation of AR protein; the proteasome inhibitor MG132 (HY-13259) abrogates the reduction of AR protein induced by ZNU-IMB-Z15, while ZNU-IMB-Z15 enhances AR ubiquitination, indicating that it promotes AR degradation via the ubiquitin-proteasome pathway[1].
ZNU-IMB-Z15 (0.2-5 μM; 24 h) dose-dependently increases cleaved PARP levels and induces apoptosis in VCaP and 22Rv1 cells, whereas exerts weak effects on apoptosis in AR-negative DU145 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LNCaP, 22Rv1, VCaP human prostate cancer cells
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Concentration:0.2, 1.0, 5.0 μM
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Incubation Time:24 h
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Result:Dose-dependently inhibited DHT-activated AR downstream genes including PSA, PMEPA1, and TMPRSS2 in LNCaP cells.
Decreased DHT-induced PSA mRNA levels in 22Rv1 and VCaP cells.
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Cell Line:LNCaP, 22Rv1, VCaP human prostate cancer cells
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Concentration:0.2, 1.0, 5.0 μM
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Incubation Time:24 h
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Result:Reduced AR protein levels and decreased ARV7 in 22Rv1 cells.
AR DC50 values were 1.05 μM in LNCaP and 1.16 μM in 22Rv1 cells, and ARV7 DC50 was 2.24 μM in 22Rv1 cells.
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Cell Line:LNCaP human prostate cancer cells
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Concentration:5.0 μM
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Incubation Time:4 h
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Result:Blocked DHT-induced translocation of AR from the cytoplasm to the nucleus.
Reduced the nuclear/cytoplasmic AR ratio to levels similar to enzalutamide treatment.
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Cell Line:VCaP, 22Rv1, DU145 human prostate cancer cells
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Concentration:0.2, 1.0, 5.0 μM
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Incubation Time:24 h
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Result:Increased cleaved PARP in VCaP and 22Rv1 cells but showed little effect in AR-negative DU145 cells.
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Cell Line:22Rv1; PC-3
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Concentration:1 μM
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Incubation Time:12-14 days
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Result:Reduced colony formation in 22Rv1 cells but showed no significant effect in PC-3 cells.
In Vivo
ZNU-IMB-Z15 (20 mg/kg; administered via oral gavage; once daily; for 21 days) inhibits the growth and reduces the weight of 22Rv1 xenograft tumors in castrated male BALB/c nude mice, while decreasing the levels of AR, ARV7, PSA and Ki-67 in tumor tissues, with no significant body weight loss observed[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, 5 weeks old, castration-resistant prostate cancer subcutaneous xenograft model)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Suppressed 22Rv1 tumor progression significantly.
Reduced tumor weight significantly.
Decreased AR, ARV7, and PSA protein levels in tumor tissues significantly.
Reduced Ki-67 and PSA protein levels in tumor tissues.
Showed no measurable side effects via body weight monitoring.
Chemical Information
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CAS No. 920915-26-0
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Appearance Solid
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Molecular Weight 411.50
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Formula C20H17N3O3S2
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Color White to off-white
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SMILES
O=C(NC1=NC(C2=CC=CS2)=CS1)C3=CC=C(OCC4=C(C)ON=C4C)C=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (243.01 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)
In Vivo:
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: ≥ 2.5 mg/mL (6.08 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
In Vivo Dissolution Calculator
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.
Purity & Documentation
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Data Sheet (291 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
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 | 2.4301 mL | 12.1507 mL | 24.3013 mL | 60.7533 mL |
| 5 mM | 0.4860 mL | 2.4301 mL | 4.8603 mL | 12.1507 mL | |
| 10 mM | 0.2430 mL | 1.2151 mL | 2.4301 mL | 6.0753 mL | |
| 15 mM | 0.1620 mL | 0.8100 mL | 1.6201 mL | 4.0502 mL | |
| 20 mM | 0.1215 mL | 0.6075 mL | 1.2151 mL | 3.0377 mL | |
| 25 mM | 0.0972 mL | 0.4860 mL | 0.9721 mL | 2.4301 mL | |
| 30 mM | 0.0810 mL | 0.4050 mL | 0.8100 mL | 2.0251 mL | |
| 40 mM | 0.0608 mL | 0.3038 mL | 0.6075 mL | 1.5188 mL | |
| 50 mM | 0.0486 mL | 0.2430 mL | 0.4860 mL | 1.2151 mL | |
| 60 mM | 0.0405 mL | 0.2025 mL | 0.4050 mL | 1.0126 mL | |
| 80 mM | 0.0304 mL | 0.1519 mL | 0.3038 mL | 0.7594 mL | |
| 100 mM | 0.0243 mL | 0.1215 mL | 0.2430 mL | 0.6075 mL |
ZNU-IMB-Z15 Related Classifications
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