一种针对人类乳头瘤病毒E7coprotein和细胞酸酶PTPN14之间的相互作用的小分子在宫癌细胞中发挥抗瘤活性
Chiara Bertagnin1, Lorenzo Messa1, Matteo Pavan2
1Department of Molecular Medicine, University of Padua, Padua, Italy.
Cancer letters
|August 2, 2023
概括
科学家们开发了一种针对人类乳头瘤病毒 (HPV) E7 coprotein 与 PTPN14 相互作用的新药. 这种化合物抑制癌细胞生长,并显示出作为HPV诱导癌症的新疗法的潜力.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 药物发现 药物发现 药物发现
背景情况:
- 人类乳头瘤病毒 (HPV) 诱导的癌症对全球健康构成重大挑战,具体治疗方法有限.
- HPV E7 瘤蛋白通过降解宿主因子来驱动癌症发生,包括酸酶 PTPN14,这对HPV瘤发生至关重要.
研究的目的:
- 确定抑制HPV E7上蛋白和PTPN14之间的相互作用的小分子化合物.
- 评估这种抑制剂对HPV阳性宫癌的治疗潜力.
主要方法:
- 针对E7/PTPN14相互作用的小分子化合物的in silico选,使用晶体结构数据.
- 在体外抑制测定和细胞研究以评估化合物的疗效.
- 对下游信号通路的分析,包括YAP穿服务.
主要成果:
- 鉴定了一种新型化合物,该化合物在体外抑制了E7/PTPN14相互作用,并恢复了癌细胞中的PTPN14水平.
- 该化合物降低了HPV阳性宫癌细胞的活力,增殖,迁移和癌症干细胞潜力.
- 治疗改变了YAP信号,并证明了针对各种高风险HPV基因型的活性.
结论:
- 这项研究介绍了E7/PTPN14相互作用的第一类抑制剂.
- 这种相互作用的药理抑制是开发针对HPV相关癌症的新型特异性疗法的可行策略.
相关概念视频
Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K


