Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

8.0K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

8.1K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

5.5K
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...
5.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.1K
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...
5.1K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

8.6K
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...
8.6K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

491
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
491

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Managing the "Three Cs" of Academic Literature Authorship: Contributions, Credit, and Conflict.

American journal of pharmaceutical education·2023
Same author

Targeting NLRP3 signaling by a novel-designed sulfonylurea compound for inhibition of microglial inflammation.

Bioorganic & medicinal chemistry·2022
Same author

The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors.

Molecules (Basel, Switzerland)·2022
Same author

Design, synthesis, and screening of sulfonylurea-derived NLRP3 inflammasome inhibitors.

Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents·2020
Same author

Towards a Better Understanding of Computational Models for Predicting DNA Methylation Effects at the Molecular Level.

Current topics in medicinal chemistry·2020
Same author

Akt Pathway Inhibition of the Solenopsin Analog, 2-Dodecylsulfanyl-1,-4,-5,-6-tetrahydropyrimidine.

Anticancer research·2019
Same journal

Exploration of a Novel Physicochemical Property Space for the Development of Antimalarial Drugs.

Current topics in medicinal chemistry·2026
Same journal

Computational Drug Design of Natural Product-Based Azole Hybrids for Multifactorial Diseases: Success Stories.

Current topics in medicinal chemistry·2026
Same journal

Simulated Natural Nanoparticles in Bai-Hu-Tang Decoction: Preparation, Characterization, Pharmacokinetics, and Antipyretic Effects.

Current topics in medicinal chemistry·2026
Same journal

Dolabellane Diterpenes from the Marine Brown Alga Dictyota dolabellana and their Potential Antiviral Activity.

Current topics in medicinal chemistry·2026
Same journal

Inhibitory Effects of Flavonoids from the Stems and Leaves of Scutellaria baicalensis Georgi on Oligodendrocyte Pyroptosis Induced by Aβ1-42.

Current topics in medicinal chemistry·2026
Same journal

Mechanism of Huangqishihu Decoction in Treating Liver Fibrosis in Rats Model via Regulation of Oxidative Stress and Nrf2 Signaling Pathway.

Current topics in medicinal chemistry·2026
See all related articles

Related Experiment Video

Updated: Dec 27, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.5K

Akt Pathway Inhibitors.

Nne E Uko1, Osman F Güner2, Diane F Matesic1

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, United States.

Current Topics in Medicinal Chemistry
|February 25, 2020
PubMed
Summary
This summary is machine-generated.

Akt inhibitors target the PI3K/Akt pathway, crucial in cancer growth. Several drugs, including ATP-competitive and allosteric inhibitors like perifosine, show promise in reducing tumor cell proliferation by decreasing Akt activity.

Keywords:
ATP inhibitorsAfuresertib (GSK2110183)Akt activationAkt binding siteAkt inhibitorsAkt kinaseCancerCapivasertib (AZD5363)Computational chemistryComputer-assisted drug designDrug designMolecular modelingP13K/Akt pathwayPKBPerifosine (KRX- 0401)PharmacophorePhosphorylationSolenopsinSolenopsin analoguesUprosertib (GSK2141795)to Ipatasertib (RG7440).

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.2K
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.2K

Related Experiment Videos

Last Updated: Dec 27, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.5K
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.2K
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.2K

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cancer remains a significant global health challenge.
  • The PI3K/Akt pathway is frequently over-activated in human cancers, driving tumor growth.
  • Targeting this pathway offers a promising strategy for cancer therapy.

Purpose of the Study:

  • To review current Akt inhibitors and their mechanisms of action.
  • To highlight promising drug candidates for cancer treatment.
  • To explore the potential of natural products and their derivatives as Akt inhibitors.

Main Methods:

  • Review of preclinical and clinical studies on Akt inhibitors.
  • Analysis of drug-target interactions, focusing on ATP-competitive and allosteric inhibition.
  • Pharmacophore modeling and computational predictions for natural product derivatives.

Main Results:

  • Several Akt inhibitors (ipatasertib, afuresertib, uprosertib, capivasertib) targeting the ATP active site demonstrate cytotoxic and antiproliferative effects.
  • Perifosine, an allosteric inhibitor, reduces Akt activity by inhibiting PH-domain dependent mechanisms.
  • Other small molecule inhibitors (MK-2206, PHT-427) and the natural product solenopsin also show potential in suppressing cancer cell growth.

Conclusions:

  • Akt inhibitors represent a vital class of anti-cancer therapeutics.
  • Both ATP-competitive and allosteric inhibitors offer distinct mechanisms for targeting the PI3K/Akt pathway.
  • Natural products like solenopsin and their derivatives warrant further investigation for novel cancer treatments.