Art. -Nr.: HY-163944

LL-K12-18

Kundenbewertung

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.

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

Reinheit: 98.42%
CAS. Nr.: 3081311-94-3
Formel: C₂₅H₃₂Cl₂N₁₀O
Molecular Weight:559.49

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

LL-K12-18 Chemical Structure

CAS. Nr.: 3081311-94-3

Größe

Preis

Verfügbarkeit

Menge

Amount: USD 0.00

* Bitte wählen Sie Menge, bevor Sie Artikel hinzufügen.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

RNA Polymerase

CDK12/Cyclin K

283.9 nM (IC₅₀)

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen :

Alle CDK Isoform-spezifische Produkte anzeigen :

Alle ATM/ATR Isoform-spezifische Produkte anzeigen :

Alle PARP Isoform-spezifische Produkte anzeigen :

In Vitro

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.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 human breast cancer cells
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)
Incubation Time:

4 h (DC₅₀ determination); 0-6 h (degradation kinetics); unspecified (cyclin K rescue assays)
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.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231 human breast cancer cells
Concentration:

25-2000 nM (cyclin/CDK selectivity assay); 2 μM (cyclin/CDK selectivity and RNA POL II phosphorylation assays)
Incubation Time:

2 h (proteomics analysis); 6 h (cyclin/CDK selectivity and RNA POL II phosphorylation assays)
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.

Real Time qPCR^[1]

Cell Line:

MDA-MB-231 human breast cancer cells
Concentration:

50 nM (DDR gene expression assay); 25-2000 nM (DNA damage/apoptosis marker assay)
Incubation Time:

6 h (DDR gene expression assay); 24 h (DNA damage/apoptosis marker assay)
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

CAS. Nr. 3081311-94-3
Appearance Solid
Molecular Weight 559.49
Formel C₂₅H₃₂Cl₂N₁₀O
Color White to off-white
SMILES

CCN1C=NC2=C1N=C(N(CC3)CCN3C(CN(CC)CC)=O)N=C2NCC4=NC5=CC(Cl)=C(C=C5N4)Cl
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.7873 mL

8.9367 mL

17.8734 mL

5 mM

0.3575 mL

1.7873 mL

3.5747 mL

10 mM

0.1787 mL

0.8937 mL

1.7873 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Zhang Z, Li Y, Yang J, et al. Dual-site molecular glues for enhancing protein-protein interactions of the CDK12-DDB1 complex[J]. Nature Communications, 2024, 15(1): 6477.

[2]. Lin S, Yang C G, Luo C, et al. Recent Advances in Dynamic Biomacromolecular Modifications and Chemical Interventions: Perspective from a Chinese Chemical Biology Consortium[J]. CCS Chemistry, 2025, 7(10): 2912-2949.

[3]. Jornet Margalef F. Molecular Dynamics Simulations of Molecular Glue Degraders: targeting the DDB1-CDK12-Cyclin K complex for Selective Protein Degradation[J]. 2025.

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Produktname:
Art. -Nr.:
Menge:
MCE Japan Authorized Agent:

Produktname:
CAS. Nr.:
Species:
Reinheit:
Menge:

LL-K12-18

Oxygen Sensing Compound Library

Glycolysis Compound Library

Cytoskeleton Compound Library

Anti-Breast Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Glucose Metabolism Compound Library

Cancer Stem Cells Compound Library

Molecular Glue Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

Cell Death Library

Serine/Threonine Kinase Inhibitor Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

High-Efficiency Gene Editing Compound Library

Apoptosis Compound Library

Cell Cycle/DNA Damage Compound Library

Epigenetics Compound Library

Kinase Inhibitor Library

PI3K/Akt/mTOR Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Alle DNA/RNA Synthesis Isoform-spezifische Produkte anzeigen

Alle CDK Isoform-spezifische Produkte anzeigen

Alle ATM/ATR Isoform-spezifische Produkte anzeigen

Alle PARP Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

LL-K12-18 Related Classifications

HY-163944 Related Classifications