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

The Ras Gene02:38

The Ras Gene

7.4K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.4K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

5.6K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.6K
Abnormal Proliferation02:23

Abnormal Proliferation

5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

9.0K
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...
9.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

8.9K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.9K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

7.6K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.6K

You might also read

Related Articles

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

Sort by
Same author

Targeting of MEK and Autophagy in Pancreatic Adenocarcinoma and Analysis of Treatment Sensitivity in Preclinical and Clinical Models: MEKiAUTO.

JCO precision oncology·2026
Same author

Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.

Nature cell biology·2026
Same author

MiR-940 Suppresses Ferroptosis by Controlling Expression of Key Regulatory Genes.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)·2026
Same author

GPX4 regulates lipid peroxidation and ferroptosis of stored red blood cells.

Blood. Red cells & iron·2026
Same author

Electroporation-Induced Gastric Cancer Models Through Epithelial-Specific Genetic Modifications.

Gastro hep advances·2026
Same author

Dissecting Polypharmacology in Phenotypic Screening to Resolve Ferroptotic and Necrotic Cell-Death Mechanisms.

ACS medicinal chemistry letters·2026
Same journal

A viral ORFeome library for systems-level genetic dissection of host-pathogen interactions.

Cell·2026
Same journal

Co-option of lysosomal machinery shapes the evolution of the intracellular photosymbiosis supporting coral reefs.

Cell·2026
Same journal

LEF1 and niche factors determine T cell stemness across chronic diseases.

Cell·2026
Same journal

Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders.

Cell·2026
Same journal

Four-dimensional molecular mapping from a spatial snapshot reveals the dynamics of hair follicle organogenesis.

Cell·2026
Same journal

Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy data.

Cell·2026
See all related articles

Related Experiment Video

Updated: Mar 7, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K

Multivalent Small-Molecule Pan-RAS Inhibitors.

Matthew E Welsch1, Anna Kaplan2, Jennifer M Chambers2

  • 1Department of Chemistry, Columbia University, New York, NY 10027, USA.

Cell
|February 25, 2017
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel small molecule that targets RAS proteins, showing anti-tumor activity in preclinical models. This pan-RAS inhibitor demonstrates potential as a new cancer therapeutic strategy.

Keywords:
GTPaseHrasKrasNrasRascancerchemical biologydrug designmultivalentsmall molecule

More Related Videos

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

3.2K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K

Related Experiment Videos

Last Updated: Mar 7, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

3.2K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Molecular Biology

Background:

  • Protein-protein interactions (PPIs) are crucial in cellular signaling, and their disruption offers therapeutic potential.
  • RAS proteins are key regulators of cell growth, and their oncogenic mutations drive many cancers.
  • Targeting RAS-effector interactions with small molecules is a promising strategy for cancer therapy.

Purpose of the Study:

  • To design and synthesize novel small molecules targeting oncogenic RAS proteins.
  • To evaluate the binding affinity and cellular effects of these pan-RAS ligands.
  • To assess the therapeutic potential of a lead compound in preclinical cancer models.

Main Methods:

  • Structure-based design of small molecules targeting adjacent sites on oncogenic KRAS.
  • Synthesis and characterization of potential pan-RAS ligands.
  • Biophysical validation of compound binding using microscale thermophoresis, NMR, and ITC.
  • Assessment of cellular lethality and metabolic stability.
  • Evaluation of anti-tumor activity in xenograft mouse models.

Main Results:

  • One compound, 3144, demonstrated binding to RAS proteins via multiple biophysical techniques.
  • Compound 3144 induced lethality in cancer cells with RAS dependency.
  • The compound exhibited metabolic stability in liver microsomes.
  • Significant anti-tumor activity was observed in xenograft mouse cancer models.

Conclusions:

  • Pan-RAS inhibition represents a viable therapeutic strategy for certain cancers.
  • Multivalent inhibitors designed using structure-based approaches can effectively target protein surfaces.
  • Small molecules targeting RAS proteins hold promise for future cancer treatments.