LL-K12-18
Based on 1 Customer Validation
LL-K12-18 is a CDK12 kinase inhibitor and a dual-site molecular glue. LL-K12-18 inhibits human CDK12 with an IC50 value of 283.9 nM, and selectively degrades cyclin K via the ubiquitin-proteasome system by stabilizing the CDK12-DDB1 complex. LL-K12-18 downregulates DNA damage response genes, reduces the phosphorylation level of CTD Ser2 in RNA polymerase II, and modulates biomarkers such as ATM, RAD51, γ-H2AX and cleaved PARP, thereby effectively inducing apoptosis and inhibiting proliferation of breast cancer cells. LL-K12-18 exhibits high target selectivity and serves as a research tool for studies on triple-negative breast cancer.
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- Pureté: 98.42%
- CAS No.: 3081311-94-3
- Formule: C25H32Cl2N10O
- Masse moléculaire:559.49
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Stockage: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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
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RNA Polymerase |
CDK12/Cyclin K 283.9 nM (IC50) |
LL-K12-18 (multiple concentrations; 120 h) potently inhibits the proliferation of MDA-MB-231 and MDA-MB-468 human breast cancer cells with sub-nanomolar potency (EC50 0.37 nM for MDA-MB-231, 0.03 nM for MDA-MB-468)[1].
LL-K12-18 (0.2-500 nM; 0-6 h) potently and rapidly degrades cyclin K in MDA-MB-231 cells via a DDB1-mediated ubiquitin-proteasome system-dependent mechanism, with minimal impact on CDK12 levels (DC50 0.38 nM)[1].
LL-K12-18 (25-2000 nM; 2-6 h) selectively degrades cyclin K (and downstream CDK13) in MDA-MB-231 cells, and specifically inhibits CDK12-mediated phosphorylation of the RNA polymerase II CTD Ser2 residue[1].
LL-K12-18 (50 nM (DDR assay); 25-2000 nM (damage/apoptosis assay); 6-24 h) downregulates DNA damage response gene expression and induces DNA damage and apoptosis in MDA-MB-231 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:0.2-500 nM (DC50 determination); 50 nM (degradation kinetics); 125-2000 nM (cyclin K rescue assays with pre-treatment inhibitors); 20-100 nM (cyclin K rescue assays with DDB1 shRNA)
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Incubation Time:4 h (DC50 determination); 0-6 h (degradation kinetics); unspecified (cyclin K rescue assays)
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Result:Degraded cyclin K with a DC50 of 0.38 nM, and almost completely degraded cyclin K at 10 nM within 4 h.
Nearly fully degraded cyclin K within 2 h at 50 nM, a faster rate than its precursor.
Induced cyclin K degradation that was rescued by pre-treatment with the proteasome inhibitor MG132, the NAE inhibitor MLN-4924, or knockdown of DDB1 via shRNA.
Had minimal effect on CDK12 protein levels at active concentrations.
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:25-2000 nM (cyclin/CDK selectivity assay); 2 μM (cyclin/CDK selectivity and RNA POL II phosphorylation assays)
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Incubation Time:2 h (proteomics analysis); 6 h (cyclin/CDK selectivity and RNA POL II phosphorylation assays)
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Result:Significantly and selectively decreased cyclin K protein levels within 2 h; also reduced CDK13 levels, but had minimal impact on other tested proteins.
Reduced only cyclin K protein levels substantially among all tested cyclins (A2, D1, E1, H, T1) and CDKs (1, 2, 4, 6, 7, 9, 12) after 6 h treatment with up to 2000 nM.
Reduced phosphorylation of Ser2 on the RNA polymerase II CTD, but had a weak effect on Ser5 phosphorylation.
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Cell Line:MDA-MB-231 human breast cancer cells
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Concentration:50 nM (DDR gene expression assay); 25-2000 nM (DNA damage/apoptosis marker assay)
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Incubation Time:6 h (DDR gene expression assay); 24 h (DNA damage/apoptosis marker assay)
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Result:Significantly reduced the mRNA levels of DDR genes (FANCI, FANCD2, RAD51, SMARCC2, ATM, ATR) in MDA-MB-231 cells, with greater inhibition than its precursor.
Reduced protein levels of ATM and RAD51, and increased levels of γ-H2AX (a DNA damage marker) and cleaved-PARP (an apoptosis marker) after 24 h treatment.
Chemical Information
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CAS No. 3081311-94-3
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Appearance Solid
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Masse moléculaire 559.49
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Formule C25H32Cl2N10O
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Color White to off-white
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SMILES
CCN1C=NC2=C1N=C(N(CC3)CCN3C(CN(CC)CC)=O)N=C2NCC4=NC5=CC(Cl)=C(C=C5N4)Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : 25 mg/mL (44.68 mM; ultrasonic and warming and heat to 60°C; 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)
Pureté et documentation
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Fiche technique (280 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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Instruction de manipulation (2659 KB)
Références
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 | 1.7873 mL | 8.9367 mL | 17.8734 mL | 44.6836 mL |
| 5 mM | 0.3575 mL | 1.7873 mL | 3.5747 mL | 8.9367 mL | |
| 10 mM | 0.1787 mL | 0.8937 mL | 1.7873 mL | 4.4684 mL | |
| 15 mM | 0.1192 mL | 0.5958 mL | 1.1916 mL | 2.9789 mL | |
| 20 mM | 0.0894 mL | 0.4468 mL | 0.8937 mL | 2.2342 mL | |
| 25 mM | 0.0715 mL | 0.3575 mL | 0.7149 mL | 1.7873 mL | |
| 30 mM | 0.0596 mL | 0.2979 mL | 0.5958 mL | 1.4895 mL | |
| 40 mM | 0.0447 mL | 0.2234 mL | 0.4468 mL | 1.1171 mL |
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