基于PI3K的抗癌药物的当前发展:设计策略,生物活性,选择性,结构-活性相关性和对接洞察力
Md Ashadul Sk1, Hemalatha K1, Gurubasavaraja Swamy Purawarga Matada1
1Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru 560107, Karnataka, India.
Bioorganic chemistry
|December 11, 2024
概括
酸丁醇-3激酶 (PI3K) 途径在许多癌症中至关重要. 本综述探讨PI3K抑制剂,它们的发展以及结构-活性关系,以克服治疗耐药性并改善癌症治疗.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- 酸-3酶 (PI3K) 途径在各种癌症中经常失调,导致瘤细胞存活,血管生成和转移.
- PI3K异型 (α,β,δ,γ) 的突变或过度表达有助于治疗耐药性,突出显示了对新型抑制剂的需求.
- 现有的PI3K抑制剂因毒性和撤回指示而面临挑战,需要创新的药物开发策略.
研究的目的:
- 审查目前用于癌症治疗的PI3K抑制剂的情况.
- 分析PI3K抑制剂的开发技术,结构-活性关系 (SAR) 和对接见解.
- 确定开发有效和安全的PI3K向药物的未来方向.
主要方法:
- 关于PI3K通路抑制剂的综合文献综述.
- 对药物化学支架及其结构-活性关系的分析.
- 检查临床试验数据和药物停药的原因.
- 包括用于合理药物设计的对接见解.
主要成果:
- 已经研究了许多使用多种支架的PI3K抑制剂 (例如, thiazole, triazine, benzimidazole).
- 了解SAR和对接为设计异形特异性和强效抑制剂提供了基础.
- 在克服耐药性和减轻与PI3K抑制相关的不良影响方面仍然存在挑战.
结论:
- 针对PI3K途径仍然是瘤学中一个有前途的战略.
- 对新型支架,SAR和理性设计的进一步研究对于开发下一代PI3K抑制剂至关重要.
- 未来的努力应集中在提高疗效,安全性和克服耐药性机制,以获得更好的患者结果.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
Targeted Cancer Therapies
7.5K
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...
7.5K
Inhibition of Cdk Activity
4.7K
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...
4.7K
Phosphoinositides and PIPs
8.4K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.4K
Drugs that Stabilize Microtubules
2.0K
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...
2.0K
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K


