Related Experiment Video

Updated: Jun 16, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

EGFR tyrosine kinase inactivation by Withacoagulin-induced conformational shift

Smita Manjari Panda1, Umakanta Tripathy1

  • 1Department of Physics, Indian Institute of Technology (Indian School of Mines) Dhanbad, Dhanbad, Jharkhand, 826004, India.

Journal of Molecular Graphics & Modelling
|June 13, 2026
PubMed

Insights

Natural compounds from medicinal plants show promise as anticancer drugs by inhibiting epidermal growth factor receptor tyrosine kinase (EGFR TK). Withacoagulin demonstrates strong binding and potential therapeutic benefits for EGFR-overexpressing cancers.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Computational Chemistry

Background:

  • Epidermal growth factor receptor (EGFR) is a key regulator of cell functions and its overexpression is linked to various cancers, making it a significant therapeutic target.
  • Natural products from medicinal plants offer a promising avenue for developing novel anticancer agents due to their diverse chemical structures and potential for targeted action.

Purpose of the Study:

  • To identify potent phytoconstituents from medicinal plants that can effectively inhibit the EGFR tyrosine kinase (EGFR TK).
  • To evaluate the drug-like properties, binding affinity, and potential toxicity of identified phytoconstituents compared to Gefitinib.

Main Methods:

  • A database of 2000 phytoconstituents was screened using molecular docking against EGFR TK, with Gefitinib as a reference drug.
  • ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) analysis and molecular dynamics (MD) simulations were performed on promising candidates.
  • Binding free energy calculations were conducted to assess the stability and strength of the interactions.

Main Results:

  • 215 phytoconstituents showed better docking scores than Gefitinib.
  • Withacoagulin (M31), LTS0153006 (M39), and Somniferanolide (M40) were identified as potent inhibitors with favorable drug-like properties and predicted low hepatotoxicity.
  • Withacoagulin exhibited superior binding affinity to EGFR TK, inducing conformational changes indicative of an inactive-like state.

Conclusions:

  • Withacoagulin is a highly promising phytoconstituent for developing novel anticancer therapeutics targeting EGFR-overexpressing cancers.
  • The identified natural compounds offer a safer alternative to existing therapies, with potential for reduced side effects like hepatotoxicity.
  • Further wet-lab validation and clinical trials are recommended to confirm the efficacy and therapeutic potential of Withacoagulin.
Keywords:
CancerEpidermal growth factor receptor (EGFR)Molecular dockingMolecular dynamics (MD) simulationPhytoconstituentsWithacoagulin

More Related Videos

A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration08:55

A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration

Published on: March 17, 2018

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...