2. Academic Validation
  3. Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities

Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities

  • J Med Chem. 2023 Mar 9;66(5):3135-3172. doi: 10.1021/acs.jmedchem.2c01242.
Pritam Maity 1,  Joydeep Chatterjee 1,  Kiran T Patil 1,  Sahil Arora 1,  Madhurendra K Katiyar 1,  Manvendra Kumar 1,  Amirreza Samarbakhsh 2,  Gaurav Joshi 3,  Priyadeep Bhutani 4,  Manoj Chugh 5,  Navnath S Gavande 2 6,  Raj Kumar 1
Affiliations

Affiliations

  • 1 Laboratory for Drug Design and Synthesis, Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, 151401 Bathinda, India.
  • 2 Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48201, United States.
  • 3 Department of Pharmaceutical Science, Hemvati Nandan Bahuguna Garhwal (A Central) University, Srinagar 246174, Dist. Garhwal (Uttarakhand), India.
  • 4 Jubilant Biosys Limited, 560022 Bangalore, India.
  • 5 In Vitro Diagnostics, Transasia BioMedical Pvt. Ltd. 400072 Mumbai, India.
  • 6 Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, United States.
PMID: 36812395 DOI: 10.1021/acs.jmedchem.2c01242
Abstract

Epidermal growth factor receptor (EGFR) is an oncogenic drug target and plays a critical role in several cellular functions including Cancer cell growth, survival, proliferation, differentiation, and motility. Several small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) have been approved for targeting intracellular and extracellular domains of EGFR, respectively. However, Cancer heterogeneity, mutations in the catalytic domain of EGFR, and persistent drug resistance limited their use. Different novel modalities are gaining a position in the limelight of anti-EGFR therapeutics to overcome such limitations. The current perspective reflects upon newer modalities, importantly the molecular degraders such as PROTACs, LYTACs, AUTECs, and ATTECs, etc., beginning with a snapshot of traditional and existing anti-EGFR therapies including small molecule inhibitors, mAbs, and antibody drug conjugates (ADCs). Further, a special emphasis has been made on the design, synthesis, successful applications, state-of-the-art, and emerging future opportunities of each discussed modality.

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