Title:An In Silico Investigation of Potential EGFR Inhibitors for the Clinical Treatment of Colorectal Cancer
VOLUME: 18 ISSUE: 27
Author(s):Manisha Majhi, Meer Asif Ali, Akanksha Limaye, Kritika Sinha, Praveena Bairagi, Megha Chouksey, Ruchi Shukla, Nisha Kanwar, Tajamul Hussain, Anuraj Nayarisseri* and Sanjeev Kumar Singh*
Affiliation:In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh
Keywords:Colorectal cancer, EGFR, ADMET, Virtual screening, Molecular docking, APC.
Abstract:Colorectal cancer possesses the third highest diagnostic rate and is the second leading cause
of cancer death in the USA as reported by NIH. Epidermal Growth Factor Receptor (EGFR), a transmembrane
protein, participates in PLC gamma-1, RAS-RAF-MEK-MAPKs, phosphatidylinositol-3
kinase, Akt pathways and plays a key role in normal functioning of cell division, cell differentiation,
apoptosis and migration. This protein is found to be overexpressed in more than 60% of the colorectal
cancers. Overexpressed EGFR advances the tumorigenic properties through cell cycle dysregulation and
activates signaling pathways linked to cancer such as WNT/β-catenin, transforming growth factor β
(TGF-β) and phosphoinositide-3-kinase (PI3K). Inhibiting the overexpressed EGFR protein has been
proposed for the treatment and many inhibitors have been reported suppressing the activity of EGFR.
However, patients in malignant state of cancer show resistance to those inhibitors, which open a wide
space to research for the discovery of novel inhibitors. The present study employed Molecular Docking
and Virtual Screening to find novel inhibitors with high affinity against EGFR. Molecular docking of
existing inhibitors resulted in the compound titled as BGB-283 (PubChem CID-89670174) having the
highest score, which was subjected to similarity search to retrieve the drugs with similar structure. The
virtual screening concluded a compound SCHEMBL18435602 (PubChem CID-126517400) which revealed
a better affinity with the target protein. A comparative study of both the compounds showed
equivalent pharmacokinetic properties. These identified drugs have a high potential to act as EGFR inhibitors
and can show promising results in the research of colorectal cancer.
