花作为KRAS向抗癌剂的来源:全面的计算评估
Osama S Mohammed1, Hezha O Rasul2, Dler M S Shwan3,4
1Department of Pharmaceutical Chemistry, College of Sciences, Charmo University, Peshawa Street, Chamchamal, Sulaymaniyah, 46023, Iraq.
Medical oncology (Northwood, London, England)
|November 30, 2025
概括
来自Calendula officinalis的天然化合物显示出在攻击性癌症中准KRAS突变的前景. 这些植物化学物质具有有利的类似药物的特性和低毒性,为抗癌药物发现提供了潜在的新途径.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 计算化学计算化学
背景情况:
- 克拉斯突变驱动胰腺,结肠直肠和NSCLC等侵袭性癌症,导致结果不佳.
- 突变的KRAS蛋白是难以治疗的标,原因是构成性激活和途径中断.
- 向KRAS突变仍然是瘤学药物开发中的一个重大挑战.
研究的目的:
- 为了识别来自Calendula officinalis的潜在抗癌药物,准KRAS突变.
- 通过计算来选植物化学物质的药物相似性和ADMET特性,以对抗KRAS突变.
- 评估具有KRAS突变的有希望的天然化合物的结合相互作用和自由能量.
主要方法:
- 利用包括利宾斯基五项规则和ADMET预测在内的计算管道进行植物化学查.
- 使用AutoDock Vina和蛋白质数据库数据验证的分子对接协议.
- 进行了分子动力学模拟和MM-GBSA分析,以评估结合的自由能量.
主要成果:
- 确定了几种具有对KRAS突变 (G12C,G13D,G12V) 强大的结合亲和力的Calendula officinalis化合物.
- 顶级化合物表现出有利的药物相似性,符合ADMET预测,并没有显示预测的致变性或肝毒性.
- 有前途的候选人表现出预测的低急性毒性,支持它们作为结构的潜力.
结论:
- 自然产品,特别是来自Calendula officinalis的植物化学物质,显示出抗癌药物发现的支架的潜力.
- 像calendasaponin D和procyanidin A2这样的化合物可以作为对KRAS驱动癌症的临床前验证的有价值的线索.
- 这项研究强调了天然化合物的治疗潜力,用于开发新型抗癌疗法,以对抗恶性瘤.
更多相关视频
相关概念视频
Inhibition of Cdk Activity
5.5K
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...
5.5K
Targeted Cancer Therapies
8.6K
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...
8.6K
M-Cdk Drives Transition Into Mitosis
6.2K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.2K
Drugs that Stabilize Microtubules
2.6K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.6K
Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
653
Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
Two synthetic agonists of THC,...
Two synthetic agonists of THC,...
653


