AccScience Publishing / ITPS / Volume 4 / Issue 1 / DOI: 10.36922/itps.v4i1.56

Molecular Docking Studies of Glabrene and Human Epidermal Growth Factor Receptor Kinase

Naresh Kumar Katari1 Rambabu Gundla1 Phani Kumar Reddy2 Anuradha Vanam3 Aruna Talatam4 Noboru Motohashi55 Rao Gollapudi6*
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1 Department of  Chemistry, School of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, Telangana, India
2 Department of Internal Medicine, NRI Academy of Medical Sciences, Guntur, Andhra Pradesh, India
3 Department of Nutrition Biology, Sri Venkateswara University, Tirupati, Andhra Pradesh, India
4 Department of Pulmonary Medicine, NRI Academy of Medical Sciences, Guntur, Andhra Pradesh, India
5 Department of Medicinal Chemistry, Meiji Pharmaceutical University, Tokyo, Japan 6 The University of Kansas, Lawrence, Kansas, United States
INNOSC Theranostics and Pharmacological Sciences 2021, 4(1), 38–49;
Submitted: 25 March 2022 | Accepted: 18 April 2022 | Published: 29 April 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( )

Background: Human epidermal growth factor receptor 2 (Her2) gene located in human chromosome17, encodes Her2 tyrosine kinase protein, and is overexpressed in breast cancer cells. Her2 is activated on phosphorylation of tyrosine by adenosine triphosphate (ATP). Nonetheless, Her2 excessively partakes in the development and prognosis of specific types of aggressive breast cancers. Therefore, Her2 inhibition therapy is primary target for the treatment of aggressive breast cancer. At present, lapatinib is one of the Food and Drug Administration approved Her2 inhibitors used in cancer therapy. In molecular docking process, glabrene with slightly higher binding energy competitively bound to the active receptor site comparable to lapatinib and ATP. Therefore, glabrene could emerge as a potential candidate for restricting Her2 overexpressed breast cancer.

Objective: The present study aimed to demonstrate the inhibitory activity of glabrene, an isoflavene and xenoestrogen found in liquorice root, along with known Her2 inhibitor, lapatinib.

Methods: ATP, lapatinib, and glabrene were docked on human Her2 protein 3D structure which revealed glabrene as a competitive Her2 inhibitor akin to lapatinib. Results: The docking results suggested the binding site similarities of ATP, lapatinib, and glabrene. The binding energies of docked ATP, lapatinib, and glabrene complexes with Her2 were −9.1 kcal/mol, −10.5 kcal/mol, and −11.3 kcal/mol, respectively.

Conclusion: The in silico docking simulation of ATP, lapatinib, and glabrene suggested that glabrene is likewise a competitive Her2 inhibitor.

Breast cancer
Human epidermal growth factor receptor 2
Adenosine triphosphate
In silico docking
Molecular dynamics

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Conflict of interest
The authors declare that they do not have any conflicts of interest of any kind for this study.
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing