Related Experiment Video

Updated: Sep 28, 2026

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

Targeting serine/threonine protein kinase B/Akt and cell-cycle checkpoint kinases for treating cancer

Qun Li1, Gui-Dong Zhu

  • 1Abbott Laboratories, Cancer Research, Global Pharmaceutical Discovery, R47S, AP10, 100 Abbott Park Rd, Abbott Park, IL 60064-6101, USA. qun.li@abbott.com

Current Topics in Medicinal Chemistry
|August 13, 2002
PubMed

Insights

Targeting specific protein kinases like PKB/Akt and checkpoint kinase 1 (Chk1) offers a cancer-specific approach, minimizing side effects associated with traditional chemotherapy and enhancing treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Protein kinases are emerging as cancer-specific molecular targets, offering an alternative to conventional chemotherapy with reduced cytotoxic side effects.
  • Protein Kinase B/Akt (PKB/Akt) is overexpressed in many human tumors, regulating apoptosis.
  • Checkpoint kinase 1 (Chk1) is a key regulator of cell-cycle checkpoints, which are often defective in cancer cells.

Purpose of the Study:

  • To review two emerging protein serine/threonine kinase targets: PKB/Akt and Chk1.
  • To discuss the potential of targeting these kinases for cancer therapy.
  • To explore the mode of action of small molecule inhibitors for these targets.

Main Methods:

  • Review of scientific literature on PKB/Akt and Chk1.
  • Analysis of the role of these kinases in cancer cell survival and proliferation.
  • Examination of the mechanisms of action of existing small molecule inhibitors.

Main Results:

  • PKB/Akt inhibitors are expected to create a wider therapeutic window by targeting apoptosis dysregulation in cancer cells.
  • Inhibiting Chk1 could sensitize cancer cells to DNA-damaging agents or radiation therapy by exploiting defective cell-cycle checkpoints.
  • A limited number of small molecule inhibitors targeting these kinases are under investigation.

Conclusions:

  • PKB/Akt and Chk1 represent promising molecular targets for developing novel, cancer-specific therapies.
  • Targeting these kinases may offer improved therapeutic windows and enhanced treatment efficacy compared to conventional chemotherapy.
  • Further research into small molecule inhibitors of PKB/Akt and Chk1 is warranted.

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

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

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...
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...
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 specific...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...
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 specific...