MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives

Teja Ram, Ankit Kumar Singh, Adarsh Kumar, Harshwardhan Singh, Prateek Pathak, Maria Grishina, Habibullah Khalilullah, Benjamin Gabriel Poulson, Abdul-Hamid M. Emwas, Amita Verma, Pradeep Kumar

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


MEK1/2 are critical components of the RAS–RAF–MEK–ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to have a MEK mutation (encoding MEK2P298L). MEK is involved in various human cancers such as non-small cell lung cancer (NSCLC), spurious melanoma, and pancreatic, colorectal, basal, breast, and liver cancer. To date, 4 MEK inhibitors i.e., trametinib, cobimetinib, selumetinib, and binimetinib have been approved by the FDA and several are under clinical trials. In this review, we have highlighted structural insights into the MEK1/2 proteins, such as the αC-helix, catalytic loop, P-loop, F-helix, hydrophobic pocket, and DFG motif. We have also discussed current issues with all FDA-approved MEK inhibitors or drugs under clinical trials and combination therapies to improve the efficacy of clinical drugs. Finally, this study addressed recent developments on synthetic MEK inhibitors (from their discovery in 1997 to 2022), their unique properties, and their relevance to MEK mutant inhibition.
Original languageEnglish (US)
JournalRSC Medicinal Chemistry
StatePublished - Aug 10 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-09-05
Acknowledgements: The authors are thankful to DST-FIST, Central University of Punjab, Bathinda, for providing the necessary facilities to compose this manuscript. PP and MG acknowledge South Ural State University, Chelyabinsk, Russia under the Priority 2030 program.


Dive into the research topics of 'MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives'. Together they form a unique fingerprint.

Cite this