Maity Subhadip, Devi Priya, Singh Aastha, Asati Vikas, Asati Vivek
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.
Department of Medical Oncology, Sri Aurobindo Medical College and PG Institute, Indore, MP, India.
Curr Top Med Chem. 2025 Jun 20. doi: 10.2174/0115680266378477250610122156.
Human Epidermal Growth Receptor (HER) plays an important role in cell signalling pathways and influences different cell functioning like angiogenesis, apoptosis, metastasis, and growth of cells. Their family includes four members with structural similarities, named EGFR/HER1, HER2, HER3, and HER4. Overexpression of these receptors is responsible for the development of cancer. EGFR/HER2 dual inhibitors, approved by the US FDA (Food and Drug Administration), include lapatinib, afatinib, neratinib, dacomitinib, etc., but these drugs lack selectivity, specificity, and undesirable adverse effects. The ultimate challenges in developing lead compounds for EGFR/HER2 dual inhibitors include achieving precision, and minimising toxicity and drug resistance. This inspires medicinal and organic chemists to design new molecules. The present manuscript focuses on the identification and development of therapeutic molecules that can inhibit the target proteins EGFR/HER2 and can further be used for the treatment of breast and lung malignancies. It also highlights the development of EGFR/HER2 dual inhibitors that belong to different structural classes like pyrimidine, quinazoline, pyridine, benzimidazole, and quinoline etc. Various parameters, such as Structure-Activity Relationships (SAR), clinical trials data, patent filed, and the molecular docking study of the most potent compounds provide a valuable asset for further designing and discovering new EGFR/HER2 dual inhibitors with potential therapeutic significances for cancer treatment.
人表皮生长受体（HER）在细胞信号通路中起重要作用，并影响细胞的不同功能，如血管生成、细胞凋亡、转移和细胞生长。它们的家族包括四个结构相似的成员，分别命名为EGFR/HER1、HER2、HER3和HER4。这些受体的过表达是癌症发生的原因。美国食品药品监督管理局（FDA）批准的EGFR/HER2双重抑制剂包括拉帕替尼、阿法替尼、来那替尼、达可替尼等，但这些药物缺乏选择性、特异性，且存在不良副作用。开发EGFR/HER2双重抑制剂先导化合物的最终挑战包括实现精准性，以及将毒性和耐药性降至最低。这激发了药物化学家和有机化学家设计新分子的灵感。本手稿重点关注能够抑制靶蛋白EGFR/HER2并可进一步用于治疗乳腺癌和肺癌的治疗性分子的鉴定和开发。它还强调了属于不同结构类别的EGFR/HER2双重抑制剂的开发，如嘧啶、喹唑啉、吡啶、苯并咪唑和喹啉等。各种参数，如构效关系（SAR）、临床试验数据、专利申请以及最有效化合物的分子对接研究，为进一步设计和发现对癌症治疗具有潜在治疗意义的新型EGFR/HER2双重抑制剂提供了宝贵的资源。
