An assessment of EGFR and HER2 inhibitors with structure activity relationship of fused pyrimidine derivatives for breast cancer: a brief review

Abstract

Epidermal growth factor receptor (EGFR) and its subtype human epidermal growth factor receptor 2 (HER2) gets activated when its endogenous ligand(s) bind to its ATP binding site of target receptors. In breast cancer (BC), EGFR and HER2 are two proteins are overexpressed which leads to overexpression of cells proliferation and decreases cell death/apoptosis. Pyrimidine is one of the most widely studied heterocyclic scaffolds for EGFR as well as HER2 inhibition. We gather some remarkable results for fused-pyrimidine derivatives on various cancerous cell lines (in-vitro) and animal (in-vivo) evaluation to highlight their potency. The heterocyclic (five, six-membered, etc.) moieties which are coupled with pyrimidine moiety are potent against EGFR and HER2 inhibitions. Hence structure-activity relationship (SAR) plays important role in study of heterocyclic moiety along pyrimidine and effects of substituents, groups for increase or decrease in the cancerous activity and toxicity. By thoughtful of fused pyrimidines SAR study, it facilitates in receiving excellent overview of the compounds by concerning of efficacy and potential summary for future EGFR inhibitors. Furthermore, we studied the in-silico interactions of synthesized compounds to evaluate binding affinity towards the key amino acids..

Communicated by Ramaswamy H. Sarma

Keywords:

• EGFR
• HER2
• ATP
• pyrimidine
• SAR

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

Authors are thankful to Indian Council of Medicinal Research (ICMR), Govt. of India, New Delhi for the financial support (Grant number: BIC/12(06)/2015).