对KRAS抑制剂用于癌症管理的分子对接分析
Israa J Hakeem1, Fatmah Hazza Alsharif2, Majidah Aljadani3
1Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
Bioinformation
|October 12, 2023
概括
研究人员对530种天然化合物选了KRAS蛋白,这是癌症治疗的关键目标. 四种化合物显示出高亲和力,这表明针对KRAS信号的新型癌症疗法的潜力.
科学领域:
- 在瘤学瘤学.
- 计算化学计算化学
- 药物发现 药物发现 药物发现
背景情况:
- 瘤性RAS蛋白质的异常信号驱动大多数人类瘤.
- 克拉斯是RAS家族的一位著名成员,是各种致命恶性瘤的关键目标.
- 克拉斯蛋白调节重要的细胞过程,包括生长,分化和亡.
研究的目的:
- 通过准KRAS来识别癌症治疗的潜在天然化合物.
- 为了对自然化合物库的KRAS蛋白进行in silico选.
主要方法:
- 在530种天然化合物的选中对KRAS蛋白进行了选.
- 合成蛋白相互作用的虚拟选和视觉检查.
- 使用计算方法评估结合亲和力.
主要成果:
- 四种化合物 (ZINC32502206,ZINC98363763,ZINC85645815,ZINC98364259) 对KRAS表现出强烈的结合亲和力 (-10.50, -10.01, -9.80, -9.70 kcal/mol).这些化合物中,KRAS的结合亲和力比较强.
- 这些亲和力超过了对照化合物AMG 510 (-9.10 kcal/mol) 的亲和力.
- 确定的化合物与KRAS活性部位的关键残留物有效相互作用.
结论:
- 已识别的天然化合物显示了针对KRAS向癌症治疗的显著潜力.
- 这些化合物可以作为开发新型抗癌药物的基础.
- 对这些化合物的进一步研究可能会导致对KRAS驱动的癌症的新治疗策略.
更多相关视频
相关概念视频
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
The Ras Gene
6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.2K
Small GTPases - Ras and Rho
4.0K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
4.0K
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
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K


