Cat. No.: HY-149209

LL-K8-22

Customer Review

Based on 1 Customer Validation

LL-K8-22 is a potent, selective and durable PROTAC CDK8-cyclin C dual degrader, with DC₅₀ values of 2.52 and 2.64 μM, respectively. LL-K8-22 also suppresses STAT1 Ser 727 phosphorylation. LL-K8-22 inhibits E2F- and MYC-driven carcinogenic transcriptional programs. LL-K8-22 can be used for triplenegative breast cancer (TNBC) research.
(Pink: CDK8 ligand (HY-168683); Blue: hyt ligand (HY-N2427); Black: linker).

For research use only. We do not sell to patients.

Purity: 99.06%
CAS No.: 3034487-84-5
Formula: C₃₇H₄₃N₅O
Molecular Weight:573.77

Storage:

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

LL-K8-22 Chemical Structure

CAS No.: 3034487-84-5

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

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

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
Chemical Information
Solvent & Solubility
- In Vitro
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

LL-K8-22 is a potent, selective and durable PROTAC CDK8-cyclin C dual degrader, with DC₅₀ values of 2.52 and 2.64 μM, respectively. LL-K8-22 also suppresses STAT1 Ser 727 phosphorylation. LL-K8-22 inhibits E2F- and MYC-driven carcinogenic transcriptional programs. LL-K8-22 can be used for triplenegative breast cancer (TNBC) research^[1]. (Pink: CDK8 ligand (HY-168683); Blue: hyt ligand (HY-N2427); Black: linker).

IC₅₀ & Target

CDK8

2.52 μM (DC₅₀)

STAT1

All PROTACs Isoforms :

All CDK Isoforms :

All STAT Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
HCT-116	IC₅₀	5.87 μM Compound: LL-K8-22	Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 4 days by Celltiter glo luminescent assay Antiproliferative activity against human HCT-116 cells assessed as inhibition of cell proliferation incubated for 4 days by Celltiter glo luminescent assay	[PMID: 36930701]
MDA-MB-231	IC₅₀	6.22 μM Compound: LL-K8-22	Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell proliferation incubated for 4 days by Celltiter glo luminescent assay Antiproliferative activity against human MDA-MB-231 cells assessed as inhibition of cell proliferation incubated for 4 days by Celltiter glo luminescent assay	[PMID: 36930701]
MDA-MB-468	IC₅₀	5.73 μM Compound: LL-K8-22	Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell proliferation incubated for 4 days by Celltiter glo luminescent assay Antiproliferative activity against human MDA-MB-468 cells assessed as inhibition of cell proliferation incubated for 4 days by Celltiter glo luminescent assay	[PMID: 36930701]

In Vitro

LL-K8-22 (0-10 μM, 24 h) degrades the CDK8-cyclin C complex in a dose-dependent manner^[1].
LL-K8-22 (0-20 μM, 4 days) suppresses tumor cell proliferation^[1].
LL-K8-22 (0-8 μM, 24 h) inhibits CDK8-cyclin C downstream signaling^[1].
LL-K8-22 significantly downregulated EAPP (E2F family binding protein)^[1].
LL-K8-22 dose not affect CDK8 and CCNC mRNA levels^[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-468 cells
Concentration:

0, 0.625, 1.25, 2.5, 5, and 10 μM
Incubation Time:

24 h
Result:

Induced selective and synchronous degradation of CDK8 and cyclin C protein expression in a dose-dependent manner with DC₅₀ of 2.52 and 2.64 μM, respectively. Significantly degraded CDK8 without reducing CDK19 (a highly homologous protein of CDK8) and did not degrade other cyclin proteins except cyclin C.

Cell Proliferation Assay^[1]

Cell Line:

MDA-MB-468, HCT-116, and MDA-MB-231 cells
Concentration:

0, 0.625, 1.25, 2.5, 5, and 10 μM
Incubation Time:

24 h
Result:

Induced selective and synchronous degradation of CDK8 and cyclin C protein expression in a dose-dependent manner with DC₅₀ of 2.52 and 2.64 μM, respectively. Significantly degraded CDK8 without reducing CDK19 (a highly homologous protein of CDK8) and did not degrade other cyclin proteins except cyclin C.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-468 cells
Concentration:

0, 2, 4, and 8 μM
Incubation Time:

24 h
Result:

Reduced Ser 2 and Ser 5 phosphorylation of the C-terminal domain of RNA pol II in a dose-dependent manner. Only inhibited the Ser 727 phosphorylation of STAT1 and did not affect Janus kinase (JAK)-mediated phosphorylation of Tyr 701.

Chemical Information

CAS No. 3034487-84-5
Appearance Solid
Molecular Weight 573.77
Formula C₃₇H₄₃N₅O
Color White to off-white
SMILES

O=C(CN1C=C(C2=CC=C(C3=CN=CC4=CC=CC=C43)C=C2)C=N1)N5CCN(CCCC67CC8CC(CC(C8)C7)C6)CC5
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

In Vitro:

DMSO : 125 mg/mL (217.86 mM; Need ultrasonic; 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

1.7429 mL

8.7143 mL

17.4286 mL

5 mM

0.3486 mL

1.7429 mL

3.4857 mL

10 mM

0.1743 mL

0.8714 mL

1.7429 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.

Molarity Calculator

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

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Dilution Calculator

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Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (274 KB)
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)
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)

References

[1]. Wang M, et al. Discovery of LL-K8-22: A Selective, Durable, and Small-Molecule Degrader of the CDK8-Cyclin C Complex. J Med Chem. 2023 Apr 13;66(7):4932-4951. [Content Brief]

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	1.7429 mL	8.7143 mL	17.4286 mL	43.5715 mL
	5 mM	0.3486 mL	1.7429 mL	3.4857 mL	8.7143 mL
	10 mM	0.1743 mL	0.8714 mL	1.7429 mL	4.3571 mL
	15 mM	0.1162 mL	0.5810 mL	1.1619 mL	2.9048 mL
	20 mM	0.0871 mL	0.4357 mL	0.8714 mL	2.1786 mL
	25 mM	0.0697 mL	0.3486 mL	0.6971 mL	1.7429 mL
	30 mM	0.0581 mL	0.2905 mL	0.5810 mL	1.4524 mL
	40 mM	0.0436 mL	0.2179 mL	0.4357 mL	1.0893 mL
	50 mM	0.0349 mL	0.1743 mL	0.3486 mL	0.8714 mL
	60 mM	0.0290 mL	0.1452 mL	0.2905 mL	0.7262 mL
	80 mM	0.0218 mL	0.1089 mL	0.2179 mL	0.5446 mL
	100 mM	0.0174 mL	0.0871 mL	0.1743 mL	0.4357 mL

Keywords

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MCE Japan Authorized Agent:

Product Name:
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LL-K8-22

Cell Cycle/DNA Damage Compound Library

Immunology/Inflammation Compound Library

JAK/STAT Compound Library

Kinase Inhibitor Library

Stem Cell Signaling Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Differentiation Inducing Compound Library

Anti-Breast Cancer Compound Library

Anti-Lung Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Obesity Compound Library

Transcription Factor-Targeted Library

Cancer Stem Cells Compound Library

PROTAC Library

Highly Selective Inhibitors Library

Anti-Hematopathy Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

Anti-Aging Compound Library Mini

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

All PROTACs Isoforms

All CDK Isoforms

All STAT Isoforms

Biological Activity

Chemical Information

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

LL-K8-22

Cell Cycle/DNA Damage Compound Library

Immunology/Inflammation Compound Library

JAK/STAT Compound Library

Kinase Inhibitor Library

Stem Cell Signaling Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Differentiation Inducing Compound Library

Anti-Breast Cancer Compound Library

Anti-Lung Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Obesity Compound Library

Transcription Factor-Targeted Library

Cancer Stem Cells Compound Library

PROTAC Library

Highly Selective Inhibitors Library

Anti-Hematopathy Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

Anti-Aging Compound Library Mini

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

All PROTACs Isoforms

All CDK Isoforms

All STAT Isoforms

Biological Activity

Chemical Information

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

LL-K8-22 Related Classifications

HY-149209 Related Classifications