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

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

13.0K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

7.5K
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...
7.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.4K
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...
3.4K
Phosphorylation01:02

Phosphorylation

49.9K
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
49.9K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.8K

You might also read

Related Articles

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

Sort by
Same author

Discovery of <b>DDO-4279</b> as a PP5 degrader for the treatment of obesity.

RSC medicinal chemistry·2026
Same author

Discovery of a Biased Kelch-like ECH-Associated Protein 1-p62 (Keap1-p62) Protein-Protein Interaction (PPI) Inhibitor for the Management of p62 Aberrant Hepatocellular Carcinoma.

Journal of medicinal chemistry·2026
Same author

Repurposing Ilaprazole as a PP5 TPR Domain Binder with Modulatory Effects on MAPK Signaling.

ACS medicinal chemistry letters·2026
Same author

Targeting Cyclic GMP-AMP Synthase: Novel Therapeutic Inhibitors for Autoimmune Diseases.

ChemMedChem·2026
Same author

Scaffold Hopping-Guided Design of Novel PIM-1 Inhibitors with Anticancer Activities.

Molecules (Basel, Switzerland)·2026
Same author

A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.

Molecules (Basel, Switzerland)·2026

Related Experiment Video

Updated: Jun 5, 2025

An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation
07:45

An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation

Published on: June 6, 2022

2.8K

Modulating Phosphorylation by Proximity-Inducing Modalities for Cancer Therapy.

Qiuyue Zhang1,2, Jia Yu1,2, Qidong You1,2

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

Journal of Medicinal Chemistry
|December 9, 2024
PubMed
Summary

New heterobifunctional molecules precisely regulate protein phosphorylation, offering a promising strategy for cancer therapy by targeting aberrant phosphorylation. These novel approaches aim to overcome limitations of traditional modulators for improved drug design.

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

7.9K
Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.4K

Related Experiment Videos

Last Updated: Jun 5, 2025

An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation
07:45

An Optimized Single-Molecule Pull-Down Assay for Quantification of Protein Phosphorylation

Published on: June 6, 2022

2.8K
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

7.9K
Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.4K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Abnormal protein phosphorylation is a hallmark of various diseases, especially cancer.
  • Traditional small-molecule kinase/phosphatase modulators face challenges in achieving precise phosphorylation control.
  • Heterobifunctional molecules offer a novel approach for targeted phosphorylation regulation.

Purpose of the Study:

  • To review drug targets with aberrant phosphorylation in cancer.
  • To highlight the therapeutic potential of correcting protein phosphorylation in cancer.
  • To explore the design strategies and features of emerging heterobifunctional molecules for phosphorylation regulation.

Main Methods:

  • Literature review of aberrant phosphorylation targets in cancer.
  • Analysis of reported heterobifunctional molecules (e.g., PHICSs, PHORCs) for phosphorylation regulation.
  • Systematic elaboration of the link between aberrant phosphorylation and cancer.

Main Results:

  • Identified key drug targets with aberrant phosphorylation in various cancers.
  • Demonstrated the potential of heterobifunctional molecules in recruiting kinases or phosphatases to specific proteins.
  • Highlighted current design strategies and characteristics of these novel molecular agents.

Conclusions:

  • Heterobifunctional molecules represent a significant advancement in targeting aberrant phosphorylation for cancer therapy.
  • Further research into these molecules could overcome existing challenges and pave the way for new drug development.
  • Precise phosphorylation regulation holds promise for innovative cancer treatment strategies.