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相关概念视频

Prodrugs01:30

Prodrugs

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Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome...
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Drug Biotransformation: Overview01:16

Drug Biotransformation: Overview

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Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
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Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
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Carrier-Mediated Transport01:06

Carrier-Mediated Transport

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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...
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Bioavailability Enhancement: Drug Stability Enhancement and GI Retention01:05

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Body:Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
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相关实验视频

Updated: Jan 15, 2026

Targeted Plasma Membrane Delivery of a Hydrophobic Cargo Encapsulated in a Liquid Crystal Nanoparticle Carrier
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劫持细胞外向蛋白质降解剂-药物结合剂以提高药物输送

Fangzhu Zhao1, Yan Wu1, Kaitlin Schaefer1

  • 1Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158, United States.

Journal of the American Chemical Society
|October 15, 2025
PubMed
概括

降解剂-药物合物 (DDC) 通过结合抗体-药物合物和细胞外向蛋白质降解来增强癌症治疗. DDCs改善了溶解体的传递和细胞毒性,提供了下一代治疗选择.

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科学领域:

  • 癌症学
  • 分子生物学
  • 药物开发

背景情况:

  • 基于抗体的治疗对瘤细胞至关重要.
  • 抗体与药物结合物 (ADC) 和细胞外向蛋白降解 (eTPD) 依赖于溶酶体贩运.
  • 由于抗原内化的效率,ADCs面临局限性,而eTPD缺乏细胞毒性.

研究的目的:

  • 开发新的降解剂-药物合物 (DDC),克服ADC和eTPD的局限性.
  • 利用eTPD的内细胞和循环能力来增强 lysosomal 的传递.
  • 提高细胞毒性,扩大抗体治疗的效用.

主要方法:

  • 使用快速内化受体的DDCs的开发:低密度脂蛋白受体 (LDLR) 和化学因子受体 (CXCR7).
  • 评估细胞外膜蛋白的溶解体传递效率和降解.
  • 与常规ADC相比,DDC细胞毒性在体外的评估.

主要成果:

  • 基于LDLR的降解剂证明了细胞外膜蛋白的有效和选择性降解.
  • 与常规ADC相比,DDC具有细胞毒性有效载荷,在体外显示出增强的细胞毒性.
  • DDCs的双重模式解决了当前抗体治疗中的内化和功效挑战.

结论:

  • DDCs是一个有前途的下一代抗体治疗策略.
  • 这种方法增强了溶酶体传递和细胞毒性疗效.
  • DDCs提供了更广泛的实用性和更高的疗效,扩大了基于抗体的治疗选择.