YJ9069
Based on 1 Customer Validation
YJ9069 is a CDK12/CDK13 PROTAC degrader. YJ9069 induces proteasome-dependent degradation of CDK12 and CDK13, and inhibits serine 2 phosphorylation of RNA polymerase II (RNA polymerase II). YJ9069 triggers gene length-dependent transcription elongation defects, reduces the expression of DNA damage response genes, and induces DNA damage, cell cycle arrest and apoptosis. YJ9069 inhibits tumor growth in prostate cancer models. YJ9069 can be used for the research of prostate cancer, Ewing sarcoma and breast cancer.
(Pink: CDK12 and CDK13 ligand (HY-168658); Blue: Cereblon ligand (HY-103596); Black: linker (HY-W015967)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C46H46N10O7
- Peso molecular:850.92
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Almacenamiento:
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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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CDK12 |
CDK13 |
YJ9069 (0.2-500 nM; 0-15 h) induces dose- and time-dependent degradation of CDK12 and CDK13, and inhibits p-Ser2 of RNA polymerase II, in VCaP prostate cancer cells[1].
YJ9069 (20-200 nM; up to 80 h for VCaP; 0.2-2 μM; up to 100 h for 22Rv1, RWPE, BPH-1) potently and dose-dependently inhibits the proliferation of VCaP and 22Rv1 prostate cancer cells, while exerting no effect on benign RWPE and BPH-1 prostate cells[1].
YJ9069 (for 5 days) exhibits selective cytotoxicity against prostate cancer cells and breast cancer cells (IC50 22.9-2386 nM), with stronger toxicity than that against immortalized benign cells (IC50 >10 μM), and inhibits the viability of AR-positive prostate cancer cells, AR-positive breast cancer cells, and EWS-FLI1-positive Ewing sarcoma cells[1].
YJ9069 (200 nM; 12 h) induces significant DNA damage in VCaP prostate cancer cells[1].
YJ9069 (50 nM; 4-15 h) downregulates key DDR genes (BRCA1, ATM, ATR, FANC1, Rad51) in a time-dependent manner in VCaP prostate cancer cells[1].
YJ9069 (500 nM; 2-12 h) induces gene length-dependent transcriptional downregulation in VCaP prostate cancer cells, with the most pronounced effect on long genes, and triggers time-dependent transcriptional elongation arrest of long genes, while exerting no effect on short genes[1].
YJ9069 (100-500 nM; 15 h) induces dose-dependent subG1 cell cycle arrest in VCaP prostate cancer cells[1].
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:0.2, 1, 5, 20, 100 nM (6 h incubation); 500 nM (time-course incubation)
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Incubation Time:6 h (dose-response); 0, 1, 2, 4, 8, 15 hr (time-course)
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Result:Induced dose-dependent degradation of CDK12 and CDK13, with reduced protein levels visible at concentrations as low as 0.2 nM after 6 h.
Triggered time-dependent degradation of CDK12 and CDK13 at 500 nM, with noticeable reduction starting at 2 h and nearly complete degradation by 15 h.
Inhibited phosphorylation of RNA polymerase II at serine 2 in both dose- and time-dependent manners.
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Cell Line:VCaP, 22Rv1 prostate cancer cells; RWPE, BPH-1 benign prostate cells
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Concentration:20, 50, 100, 200 nM (VCaP); 0.2, 0.5, 1, 2 μM (22Rv1, RWPE, BPH-1)
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Incubation Time:up to 80 h (VCaP); up to 100 h (22Rv1, RWPE, BPH-1)
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Result:Inhibited proliferation of VCaP and 22Rv1 prostate cancer cells in a dose-dependent manner, with higher concentrations leading to greater and more rapid reduction in cell confluence.
Showed no antiproliferative effect on benign RWPE and BPH-1 prostate cells at parallel concentrations, with confluence levels matching DMSO control.
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Cell Line:VCaP prostate cancer cells
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Concentration:50 nM
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Incubation Time:4, 8, 15 h
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Result:Caused significant time-dependent downregulation of DDR genes including BRCA1, ATM, ATR, FANC1, and Rad51.
Downregulation was detectable as early as 4 hours and became more pronounced at 8 and 15 hours.
EZH2 expression was not significantly affected.
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Cell Line:VCaP prostate cancer cells
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Concentration:100-500 nM
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Incubation Time:15 h
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Result:Induced dose-dependent subG1 cell cycle arrest, with subG1 population increasing from 13.4% (DMSO control) to 32.7% (100 nM) and 48.1% (500 nM).
Caused concurrent decreases in G1, S, and G2/M phase populations.
YJ9069 (30 mg/kg; intravenous injection; three times per week for 21 consecutive days) induces complete tumor regression in all WA74 PDX mice[1].
YJ9069 (30 mg/kg; intravenous injection; three times per week) significantly inhibits tumor growth in PC310 PDX mice, with partial tumors showing partial remission[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CB17SCID (male, 6 weeks old, castration-resistant VCaP cell-derived xenograft model)[1]
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Dosage:30 mg/kg
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Administration:i.v.; 3 times/week; 18 days
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Result:Significantly decreased tumor CDK12 and CDK13 protein levels.
Increased cleaved PARP.
Reduced CDK12 IHC staining.
Elevated cleaved PARP and TUNEL signals.
Decreased DDR gene expression (ATM, ATR, BRCA1) in tumors.
Significantly reduced tumor volume compared to vehicle control.
Decreased tumor weight.
Induced tumor regression exceeding 50% in 73% of treated animals.
Achieved 82% partial response and 18% stable disease by RECIST criteria.
Caused less than 20% body weight loss during treatment.
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Animal Model:CB17SCID (male, 6 weeks old, WA74 patient-derived xenograft model)[1]
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Dosage:30 mg/kg
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Administration:i.v.; 2 times/week; 21 days; i.v.; 3 times/week; 21 days
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Result:Significantly reduced tumor volume and weight compared to vehicle control for both dosing schedules.
Induced tumor regression in all treated animals with 100% partial response by RECIST criteria for the 3 times/week schedule.
Resulted in 43% partial response, 43% stable disease, and 14% progressive disease by RECIST criteria for the 2 times/week schedule.
Showed tumor regression changes including hyalinization, remnant tumor nodules, and collagenization bands via H&E staining.
Caused less than 20% body weight loss during treatment.
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Animal Model:CB17SCID (male, 6 weeks old, PC310 patient-derived xenograft model)[1]
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Dosage:30 mg/kg
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Administration:i.v.; 3 times/week
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Result:Significantly reduced tumor volume and weight compared to vehicle control.
Achieved 6% partial response, 31% stable disease, and 63% progressive disease by RECIST criteria.
Showed tumor regression changes including hyalinization, remnant tumor nodules, and collagenization bands via H&E staining.
Caused less than 20% body weight loss during treatment.
Chemical Information
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Appearance Solid
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Peso molecular 850.92
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Fòrmula C46H46N10O7
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Color White to off-white
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SMILES
O=C(NCC1=CC=CC=C1)N(C2=CN=C(N3CCN(C(COC4=C5C(C(N(C6CCC(NC6=O)=O)C5=O)=O)=CC=C4)=O)CC3)C=C2)[C@H](CC7)CC[C@@H]7NC8=NC=C9C(C=CC=C9)=N8
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvente y solubilidad
DMSO : ≥ 50 mg/mL (58.76 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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 (sealed storage, away from moisture and light). 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 (sealed storage, away from moisture and light). 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)
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
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 (sealed storage, away from moisture and light). 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 |
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| DMSO | 1 mM | 1.1752 mL | 5.8760 mL | 11.7520 mL | 29.3800 mL |
| 5 mM | 0.2350 mL | 1.1752 mL | 2.3504 mL | 5.8760 mL | |
| 10 mM | 0.1175 mL | 0.5876 mL | 1.1752 mL | 2.9380 mL | |
| 15 mM | 0.0783 mL | 0.3917 mL | 0.7835 mL | 1.9587 mL | |
| 20 mM | 0.0588 mL | 0.2938 mL | 0.5876 mL | 1.4690 mL | |
| 25 mM | 0.0470 mL | 0.2350 mL | 0.4701 mL | 1.1752 mL | |
| 30 mM | 0.0392 mL | 0.1959 mL | 0.3917 mL | 0.9793 mL | |
| 40 mM | 0.0294 mL | 0.1469 mL | 0.2938 mL | 0.7345 mL | |
| 50 mM | 0.0235 mL | 0.1175 mL | 0.2350 mL | 0.5876 mL |
YJ9069 Related Classifications
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