YJ1206
Based on 1 Customer Validation
YJ1206 is an orally active selective CDK12/CDK13 PROTAC degrader. YJ1206 induces DNA damage and genomic instability, activates the AKT pathway, and triggers apoptosis. YJ1206 reduces tumor cell viability, inhibits tumor growth, and attenuates tumor cell dissemination. YJ1206 is applicable to research related to prostate cancer and high-grade serous tubo-ovarian cancer.
(Pink: CDK12 and CDK13 ligand (HY-168658); Blue: Cereblon E3 ligase ligand; Black: linker).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 97.26%
- No. CAS: 3053716-98-3
- Fòrmula: C49H52FN11O5
- Peso molecular:894.01
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Almacenamiento:Powder -20°C, 3 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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CDK12 |
CDK13 |
YJ1206 (0.2-100 nM; 4 h) potently and dose-dependently degrades CDK12 and CDK13 proteins in VCaP prostate cancer cells[1].
YJ1206 (for 5 days) inhibits the viability of VCaP prostate cancer cells, with an IC50 of 12.55 nM[1].
YJ1206 (500 nM; 8 h) selectively degrades CDK12, CDK13 and CCNK in 22Rv1 prostate cancer cells, with extremely weak off-target protein degradation activity[1].
YJ1206 induces gene length-dependent transcription elongation defects in VCaP prostate cancer cells, specifically manifesting as inhibition of long gene expression, alteration of DDR and AKT-mTOR pathway activities, and induction of DNA damage-related changes in gene expression[1].
YJ1206 (500 nM; 15 h) activates the AKT pathway in VCaP and 22Rv1 prostate cancer cells by increasing the phosphorylation levels of AKTS473, PRAS40 and S6[1].
YJ1206 (0.030-30 μM; 5 days) potently reduces the viability of 6227_KO PRN;Cdk12KO and 6137_J PRN;Cdk12HET mouse ovarian cancer cells, with an IC50 value of approximately 212 nM; whereas it shows weaker efficacy against 15973_WT PRN cells, with an IC50 value of 3337 nM[2].
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
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Incubation Time:4 h
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Result:Degraded CDK12 and CDK13 proteins in a dose-dependent manner, with significant reduction observed at concentrations starting from 0.2 nM.
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Cell Line:15973_WT PRN, 6227_KO PRN;Cdk12KO, 6137_J PRN;Cdk12HET
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Concentration:0.030, 0.060, 0.12, 0.24, 0.48, 0.96, 1.9, 3.8, 7.6, 15, 30 μM
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Incubation Time:5 days
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Result:Reduced cell viability in a dose-dependent manner across all three cell lines, with significantly greater potency in CDK12-deficient lines.
Exhibited an IC50 value of 3337 nM in 15973_WT PRN cells.
Exhibited IC50 values of 214.8 nM and 211.9 nM in 6227_KO PRN;Cdk12KO and 6137_J PRN;Cdk12HET cells, respectively.
YJ1206 (100 mg/kg; p.o.; three times per week) significantly inhibits tumor growth in the WA74 PDX prostate cancer mouse model, induces regression in 19% of tumors, and causes no significant body weight loss[1].
YJ1206 (100 mg/kg; p.o.; three times per week; for 4 consecutive weeks) moderately inhibits tumor growth in castrated 22Rv1 xenograft mouse models[1].
YJ1206 (50-100 mg/kg; p.o.; three times per week) significantly inhibits the growth of CDK12-deficient ovarian cancer subcutaneous allografts in C57BL/6J mice, with a more pronounced therapeutic effect observed at the 100 mg/kg dose[2].
Oral administration of YJ1206 at a dose of 100 mg/kg three times per week significantly inhibits the growth of subcutaneous xenografts of human CDK12-knockout ovarian cancer in NSG mice[2].
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)[1]
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Dosage:100 mg/kg
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Administration:p.o.; 3x/week; 5 days/31 days
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Result:Completely abrogated CDK12, CDK13, and CCNK protein levels in tumors.
Increased levels of cleaved PARP and γ-H2AX.
Significantly elevated cleaved PARP and TUNEL staining scores compared to vehicle controls.
Exhibited moderate anti-tumor efficacy: 80% of tumors showed progressive disease, 15% showed stable disease, and 5% showed partial response.
Significantly reduced mean tumor volume and weight compared to vehicle controls.
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Animal Model:CB17SCID (male, 6 weeks old)[1]
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Dosage:100 mg/kg
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Administration:p.o.; 3x/week
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Result:Significantly suppressed tumor growth, resulting in drastically reduced mean tumor volume and weight compared to vehicle controls.
Induced partial response (regression) in 19% of treated tumors.
Caused no significant changes in animal body weights.
Induced tumor regression characterized by hyalinization, remnant tumor nodules, and degenerative cells via histopathological analysis.\nExhibited mild to moderate anti-tumor efficacy, with all treated tumors showing progressive disease but significantly reduced mean tumor volume and weight compared to vehicle controls.
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Animal Model:C57BL/6J mice (female)[2]
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Dosage:50 mg/kg; 100 mg/kg
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Administration:p.o.; 3 times/wk
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Result:Reduced tumor volume to ~150 mm3 by day 20 (50 mg/kg dose) compared to ~320 mm3 in vehicle controls.
Reduced tumor volume to ~100 mm3 by day 20 (100 mg/kg dose) compared to ~320 mm3 in vehicle controls, with p<0.001 for both doses vs. vehicle.
Showed no obvious toxicity as measured by percent change in body weight.
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Animal Model:NSG mice[2]
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Dosage:100 mg/kg
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Administration:p.o.; 3 times/wk
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Result:Reduced tumor volume to ~150 mm3 by day 20 compared to ~300 mm3 in vehicle controls, with p<0.001.
Chemical Information
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No. CAS 3053716-98-3
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Appearance Solid
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Peso molecular 894.01
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Fòrmula C49H52FN11O5
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Color Light yellow to yellow
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SMILES
O=C(NCC1=CC=CC=C1)N(C2=CN=C(N3CCN(C4CCN(C5=C(F)C=C(C(N(C6CCC(NC6=O)=O)C7=O)=O)C7=C5)CC4)CC3)C=C2)[C@H](CC8)CC[C@@H]8NC9=NC=C%10C(C=CC=C%10)=N9
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvente y solubilidad
DMSO : 66.67 mg/mL (74.57 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: ≥ 1 mg/mL (1.12 mM); Clear solution
This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 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: 1 mg/mL (1.12 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 1 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 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 (280 KB)
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SDS (252 KB)
- English - EN (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
[1]. Chang Y, et al. Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition. Cell Rep Med. 2024;5(10):101752. [Content Brief]
[2]. Tien JC, et al. Defining CDK12 as a tumor suppressor and therapeutic target in mouse models of tubo-ovarian high-grade serous carcinoma. Proc Natl Acad Sci U S A. 2025;122(24):e2426909122. [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 |
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| DMSO | 1 mM | 1.1186 mL | 5.5928 mL | 11.1856 mL | 27.9639 mL |
| 5 mM | 0.2237 mL | 1.1186 mL | 2.2371 mL | 5.5928 mL | |
| 10 mM | 0.1119 mL | 0.5593 mL | 1.1186 mL | 2.7964 mL | |
| 15 mM | 0.0746 mL | 0.3729 mL | 0.7457 mL | 1.8643 mL | |
| 20 mM | 0.0559 mL | 0.2796 mL | 0.5593 mL | 1.3982 mL | |
| 25 mM | 0.0447 mL | 0.2237 mL | 0.4474 mL | 1.1186 mL | |
| 30 mM | 0.0373 mL | 0.1864 mL | 0.3729 mL | 0.9321 mL | |
| 40 mM | 0.0280 mL | 0.1398 mL | 0.2796 mL | 0.6991 mL | |
| 50 mM | 0.0224 mL | 0.1119 mL | 0.2237 mL | 0.5593 mL | |
| 60 mM | 0.0186 mL | 0.0932 mL | 0.1864 mL | 0.4661 mL |
YJ1206 Related Classifications
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