Target intelligence / Profile preview

Cyclin-dependent kinase 1, Cyclin-dependent kinase 2, Cyclin-dependent kinase 4, Cyclin-dependent kinase 5, Cyclin-dependent kinase 6 (CDK1, CDK2, CDK4, CDK5, CDK6)

Target
CDK1, CDK2, CDK4, CDK5, CDK6
Molecular classification
Enzyme, Protein kinase (specifically, serine/threonine kinase), Cell cycle regulator (for CDK1, CDK2, CDK4, CDK6), Neuronal kinase (particularly for CDK5), Cyclin-dependent kinase family
01

Overview

Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases critical for the regulation of the eukaryotic cell cycle, transcription, neuronal function, DNA repair, metabolism, and more. Their enzymatic activity is tightly controlled by association with cyclins and kinase inhibitors. CDK1, CDK2, CDK4, and CDK6 drive distinct cell cycle transitions (CDK4/6: G1 phase, CDK2: S phase, CDK1: G2/M transition and mitosis), while CDK5 is primarily involved in neuronal development and function, though also involved in cancer progression and other cellular processes. Aberrant regulation of CDKs is a hallmark of many cancers and some neurodegenerative diseases, making them major targets for therapeutic intervention with several drugs now approved for clinical use[1][2][3][4][5][6][7][8].

Other names
Cdc2, cell division control protein 2 homologcyclin-dependent kinase 2cyclin-dependent kinase 4cyclin-dependent kinase 5cyclin-dependent kinase 6CDKscell cycle kinasesserine/threonine kinases
02

Mechanism of action

Small molecule inhibition of kinase activity (competitive inhibition at ATP-binding site). Prevention of cell cycle progression leading to cell cycle arrest (usually G1 or G2/M). Induction of apoptosis in malignant cells. Reduction in phosphorylation of key substrates such as Rb (retinoblastoma protein).

03

Biological functions

Cell cycle progression and regulation (CDK1, CDK2, CDK4, CDK6)Cell proliferationApoptosis regulationDNA damage repairDifferentiationControl of cell death and survivalNeuronal development and signaling (CDK5)Immune response modulation (for certain CDKs, like CDK5)Metabolic regulation
04

Disease associations

Cancer (all, very prominent for CDK4, CDK6, CDK1, CDK2)Neurodegenerative disease (notably for CDK5)Cardiovascular diseaseInflammationCell-cycle associated disordersStroke (CDK5)
05

Safety considerations

Myelosuppression, especially neutropenia (with CDK4/6 inhibitors)QT prolongation (some inhibitors)Gastrointestinal toxicity (e.g., diarrhea with abemaciclib)Neurotoxicity (CDK5-specific inhibitors, risk in neuronal tissues)Off-target effects due to structural similarity among kinases
06

Interacting drugs

Palbociclib (CDK4/6 inhibitor)

7 more in the full profile.

07

Biomarkers

Phosphorylation status of retinoblastoma protein (pRb)Expression of cyclin D or cyclin E (CDK4/6 and CDK2)Levels of p16INK4A (CDK4/6 inhibitor protein, cancer context)Ki-67 (proliferation marker, cancer)

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