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.
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DOI：
10.1021/acs.jmedchem.2c01242
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发表时间：
2023-02
影响因子：
7.3
通讯作者：
Pritam Maity;Joydeep Chatterjee;Kiran T Patil;Sahil Arora;Madhurendra K Katiyar;Manvendra Kumar;Amirreza Samarbakhsh;G. Joshi;Priyadeep Bhutani;M. Chugh;Navnath S. Gavande;Raj Kumar
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作者：
Pritam Maity;Joydeep Chatterjee;Kiran T Patil;Sahil Arora;Madhurendra K Katiyar;Manvendra Kumar;Amirreza Samarbakhsh;G. Joshi;Priyadeep Bhutani;M. Chugh;Navnath S. Gavande;Raj Kumar
表皮生长因子受体（EGFR）是一种致癌药物靶标，在多种细胞功能中起关键作用，包括癌细胞生长、存活、增殖、分化和运动。几种小分子酪氨酸激酶抑制剂（TKI）和单克隆抗体（mAb）已分别获批用于靶向EGFR的细胞内和细胞外结构域。然而，癌症的异质性、EGFR催化结构域的突变和持续的耐药性限制了它们的使用。不同的新模式在抗EGFR治疗的聚光灯下获得了地位，以克服这些限制。目前的观点反映在较新的模式，重要的是分子降解剂，如PROTAC，LYTAC，AUTEC和ATTEC等，从传统和现有的抗EGFR疗法的快照开始，包括小分子抑制剂、mAb和抗体药物缀合物（ADC）。此外，一个特别强调的设计，合成，成功的应用，国家的最先进的，和新兴的未来的机会，每一个讨论的方式。
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.