Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Hyderabad campus, Jawahar Nagar, Hyderabad, 500078, Telangana, India.
Cancer Research Group, Centre for Human Diseases Research, Birla Institute of Technology & Science, Pilani, Hyderabad campus, Jawahar Nagar, Hyderabad, 500078, Telangana, India.
Future Med Chem. 2022 Apr;14(7):463-478. doi: 10.4155/fmc-2021-0205. Epub 2022 Feb 15.
Epidermal growth factor receptor-tyrosine kinase (EGFR-TK) is a well-known hallmark of oral and oropharyngeal cancers, as its overexpression leads to poor prognosis and malignancy. The activating EGFR mutations (particularly T790M and L858R double mutant) are a major challenge causing drug resistance, especially in the treatment of oral cancers. This paper is an effort to exploit both structure-based and ligand-based pharmacophore modeling to discover EGFR-TK inhibitors, which show inhibition of proliferation of erlotinib-resistant FaDu and Cal27 oral cancer cells. Interestingly, the hit compound also showed an effect on the downstream glucose and lactate metabolism pathways. The results indicate the potential of to be developed as an EGFR-based metabolic inhibitor for oral cancer treatment.
表皮生长因子受体-酪氨酸激酶（EGFR-TK）是口腔和口咽癌的一个著名特征，因为其过度表达导致预后不良和恶性。激活的 EGFR 突变（特别是 T790M 和 L858R 双突变）是导致耐药性的主要挑战，特别是在口腔癌的治疗中。本文旨在利用基于结构和基于配体的药效团模型来发现 EGFR-TK 抑制剂，这些抑制剂显示出对厄洛替尼耐药的 FaDu 和 Cal27 口腔癌细胞增殖的抑制作用。有趣的是，命中化合物 还对下游葡萄糖和乳酸代谢途径产生了影响。结果表明， 有潜力开发为基于 EGFR 的代谢抑制剂，用于口腔癌治疗。
