YJ1206 TFA
YJ1206 TFA is an orally active selective CDK12/CDK13 PROTAC degrader. YJ1206 TFA induces DNA damage and genomic instability, activates the AKT pathway, and triggers apoptosis. YJ1206 TFA reduces tumor cell viability, inhibits tumor growth, and attenuates tumor cell dissemination. YJ1206 TFA 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).
For research use only. We do not sell to patients.
- Formula: C51H53F4N11O7
- Molecular Weight:1008.03
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Storage:
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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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
All PROTACs Isoforms
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Biological Activity
Description
IC50 & Target
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CDK12 |
CDK13 |
In Vitro
YJ1206 (0.2-100 nM; 4 h) TFA potently and dose-dependently degrades CDK12 and CDK13 proteins in VCaP prostate cancer cells[1].
YJ1206 (for 5 days) TFA inhibits the viability of VCaP prostate cancer cells, with an IC50 of 12.55 nM[1].
YJ1206 (500 nM; 8 h) TFA selectively degrades CDK12, CDK13 and CCNK in 22Rv1 prostate cancer cells, with extremely weak off-target protein degradation activity[1].
YJ1206 TFA 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) TFA 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) TFA 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.
In Vivo
YJ1206 (100 mg/kg; p.o.; three times per week) TFA 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) TFA moderately inhibits tumor growth in castrated 22Rv1 xenograft mouse models[1].
YJ1206 (50-100 mg/kg; p.o.; three times per week) TFA 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 TFA 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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Molecular Weight 1008.03
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Formula C51H53F4N11O7
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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.O=C(O)C(F)(F)F
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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.
Solvent & Solubility
In Vitro:
DMSO : ≥ 100 mg/mL (99.20 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
References
[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
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 0.9920 mL | 4.9602 mL | 9.9203 mL | 24.8008 mL |
| 5 mM | 0.1984 mL | 0.9920 mL | 1.9841 mL | 4.9602 mL | |
| 10 mM | 0.0992 mL | 0.4960 mL | 0.9920 mL | 2.4801 mL | |
| 15 mM | 0.0661 mL | 0.3307 mL | 0.6614 mL | 1.6534 mL | |
| 20 mM | 0.0496 mL | 0.2480 mL | 0.4960 mL | 1.2400 mL | |
| 25 mM | 0.0397 mL | 0.1984 mL | 0.3968 mL | 0.9920 mL | |
| 30 mM | 0.0331 mL | 0.1653 mL | 0.3307 mL | 0.8267 mL | |
| 40 mM | 0.0248 mL | 0.1240 mL | 0.2480 mL | 0.6200 mL | |
| 50 mM | 0.0198 mL | 0.0992 mL | 0.1984 mL | 0.4960 mL | |
| 60 mM | 0.0165 mL | 0.0827 mL | 0.1653 mL | 0.4133 mL | |
| 80 mM | 0.0124 mL | 0.0620 mL | 0.1240 mL | 0.3100 mL |
YJ1206 TFA Related Classifications
HY-168555A Related Classifications
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