相关实验视频
Updated: Jun 12, 2025

10:56
Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
11.9K
对MDM2和GSPT1的双降解剂的表征
Ira Tandon1, Paulina N Esguerra1, Chunrong Li1
1Lachman Institute for Pharmaceutical Development, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA.
European journal of medicinal chemistry
|May 29, 2025
概括
WB156是一种针对MDM2和GSPT1的新型双降解剂,有效上调p53. 这种化合物在各种癌症中表现出抗癌活性,包括野生型和突变p53.3的白血病.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 鼠双分钟2 (MDM2) 是一种经过验证的治疗标,用于稳定癌症中的瘤蛋白53 (p53).
- 之前的研究发现,WB156是一种MDM2降解剂,在急性白血病中增加p53水平.
研究的目的:
- 评估WB156在各种癌症类型中的更广泛的治疗潜力.
- 研究WB156的作用机制,特别是在抗仅MDM2降解的癌症中.
主要方法:
- 在各种癌症模型中测试WB156.
- 与另一种已知的MDM2降解剂进行比较分析.
- 评估MDM2和G1到S相过渡1 (GSPT1) 的蛋白质降解.
主要成果:
- WB156在野生型和突变型p53携带白血病中都表现出有效性.
- WB156可以作为MDM2和GSPT1.1的双降解剂.
- 在对MDM2降解无反应的癌症中,WB156通过GSPT1降解诱导了抗增殖效应.
结论:
- 据报道,WB156是第一个双MDM2/GSPT1降解器.
- WB156通过双重降解途径上调p53水平并表现出抗癌活性.
- WB156代表了一系列癌症的有希望的治疗候选者.
相关概念视频
Abnormal Proliferation
4.5K
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...
4.5K
Export of Misfolded Proteins out of the ER
3.5K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.5K

