素-甲基杂交解锁了口服生物可用的STING激动剂,用于瘤免疫治疗
Guo-Feng Xin1, Qiang-Sheng Zhu1, Nan-Nan Chen1
1State Key Laboratory of Natural Medicines, and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
European journal of medicinal chemistry
|February 3, 2026
概括
研究人员开发了一种新的福衍生物X41,作为一种强大的干扰素基因刺激剂 (STING) 激动剂. 这种小分子显示出显著的瘤生长抑制和回归,为癌症免疫治疗提供了希望.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药用化学 医学化学
背景情况:
- 干扰素基因刺激器 (STING) 激活对于瘤免疫疗法至关重要.
- 需要新的小分子刺痛激动剂用于临床开发.
研究的目的:
- 设计和优化新型非核酸刺痛激动剂.
- 为了评估主要候选药物的临床前疗效和药理动力学特性,X41.
主要方法:
- 基于结构的药物设计被用来创建福衍生物.
- 化合物X41在MC38瘤模型中表现为STING通路激活和体内疗效.
- 药理动力学研究评估了血暴露和代谢稳定性.
主要成果:
- 化合物X41表现出强大的STING激动剂活性,诱导IFN-β和CXCL10的表达.
- 口服X41在MC38模型中实现了88.04%的瘤生长抑制.
- 内X41导致50%的小鼠的瘤完全回归,具有良好的药理动力学和9.92小时的口服半衰期.
结论:
- X41是一种结构新的,口服可用的STING激动剂,具有显著的临床前疗效.
- X41在固体瘤的免疫治疗中表现出有希望的翻译潜力.
相关概念视频
Tumor Immunotherapy
1.9K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.9K
Halogens
23.6K
Group 17 elements, known as halogens, are nonmetals. At room temperature, fluorine and chlorine are gases, bromine is a liquid, and iodine a solid. Astatine is a highly unstable radioactive element, so currently, most of its properties are unknown due to its short half-life. Tennessine is a synthetic element also predicted to be in this group.
23.6K
Multiple Halogenation of Methyl Ketones: Haloform Reaction
2.9K
A method involving the transformation of methyl ketones to carboxylic acids using excess base and halogen is called the haloform reaction. It begins with the deprotonation of α hydrogen to form an enolate ion which reacts with the electrophilic halogen to give an α-halo ketone. The step continues until all the α protons are substituted to form a trihalomethyl ketone. The resulting molecule is unstable, and in the presence of a hydroxide base, it readily undergoes nucleophilic...
2.9K
Hybrid Zones
21.9K
Hybrid zones are narrow regions where two closely related species interact, mate, and produce hybrids. Relative to either parent species, hybrids may possess distinct phenotypic or genetic differences that impact their survival and reproductive success. The genetic variances introduced by hybridization influence species diversity and speciation processes within the hybrid zone.
21.9K
Bioavailability: Overview
443
Bioavailability refers to the proportion of an administered drug that reaches the systemic circulation in its active, unaltered form. It is a crucial pharmacokinetic parameter that determines the effectiveness of a drug in achieving its intended therapeutic outcomes. The route of administration significantly influences bioavailability, with intravenous administration achieving 100% bioavailability as the drug directly enters the bloodstream. In contrast, oral administration often results in...
443
Bioavailability: Overview
4.4K
Bioavailability refers to the proportion of an unaltered drug that, after administration, enters the systemic circulation and can be distributed to the desired action site. Factors such as gastrointestinal (GI) absorption and liver biotransformation influence the bioavailability of a drug when it is administered orally. When a drug is administered intravenously, it enters the systemic circulation directly; by definition, its bioavailability is assumed to be 100%. The bioavailability of an...
4.4K


