Related Experiment Video

Updated: Nov 19, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.6K

Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs

Kai Yuan1,2, Xiao Wang1,2, Haojie Dong1,2

  • 1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.

Acta Pharmaceutica Sinica. B
|February 3, 2021
PubMed

Insights

Targeting cyclin-dependent kinases 4/6 (CDK4/6) with inhibitors offers a promising cancer therapy strategy. These inhibitors selectively block cell cycle progression, balancing efficacy and toxicity for improved cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cancer is characterized by uncontrolled cell proliferation due to cell cycle dysregulation and cyclin-dependent kinases (CDKs) activation.
  • Inhibiting CDKs presents a promising strategy for developing novel anticancer therapeutics.
  • Selective CDK4/6 inhibition offers a balanced approach to anticancer efficacy and general toxicity.

Purpose of the Study:

  • To discuss the critical roles of CDK4/6 in cell cycle regulation and cancer progression.
  • To analyze the rationale behind selective CDK4/6 inhibition for cancer therapy.
  • To review advancements in selective CDK4/6 inhibitors, resistance mechanisms, and emerging degradation techniques like PROTAC.

Main Methods:

  • Literature review and analysis of current research on CDK4/6 inhibitors.
  • Discussion of the cell cycle regulation by CDK4/6.
  • Exploration of resistance mechanisms and potential solutions, including proteolysis targeting chimera (PROTAC).

Main Results:

  • Three selective CDK4/6 inhibitors are FDA-approved; 15 are in clinical trials.
  • Selective CDK4/6 inhibitors effectively regulate the cell cycle by suppressing the G1 to S phase transition.
  • Understanding resistance mechanisms is crucial for optimizing therapeutic strategies.

Conclusions:

  • Selective CDK4/6 inhibitors represent a significant advancement in cancer treatment, offering improved efficacy and reduced toxicity.
  • Ongoing research into novel inhibitors, resistance circumvention, and degradation technologies like PROTAC promises further therapeutic breakthroughs.
  • Targeted inhibition of CDK4/6 is a validated and expanding strategy in oncology.
Keywords:
AKT, protein kinase BAML, acute myeloid leukemiaCDK4/6CDKs, cyclin-dependent kinasesCIP/KIP, cyclin-dependent kinase inhibitor 1/kinase inhibitory proteinCKIs, cyclin-dependent kinase inhibitorsCPU, China Pharmaceutical UniversityCRPC, castration-resistant prostate cancerCancerCell cycleDrug resistanceER, estrogen receptorERK, extracellular regulated protein kinasesFDA, U.S. Food and Drug AdministrationFLT, fms-like tyrosine kinaseHER2, human epidermal growth factor receptor 2INK4, inhibitors of CDK4JAK, janus kinaseMCL, mantle cell lymphomaMM, multiple myelomaNSCLC, non-small cell lung cancerORR, overall response ratesPDK1, 3-phosphoinositide-dependent protein kinase 1PFS, progression-free survivalPI3K, phosphatidylinositol 3-hydroxy kinasePR, progesterone receptorPROTACPROTAC, proteolysis targeting chimeraRB, retinoblastoma proteinSPH, Shanghai Pharmaceuticals Holding Co., Ltd.STATs, signal transducers and activators of transcriptionSelectivityUNISA, University of South Australia

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.3K
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

19.1K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.3K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.1K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.2K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.5K