用新型小分子抑制剂靶向KRAS G12D和G10突变
Targeting KRAS G12D and G10 Mutations with Novel Small Molecule Inhibitors.
作者信息
Kargbo Robert B
机构信息
Usona Institute, Fitchburg, Wisconsin 53711-5300, United States.
出版信息
ACS Med Chem Lett. 2025 May 16;16(6):939-941. doi: 10.1021/acsmedchemlett.5c00264. eCollection 2025 Jun 12.
Abstract
KRAS mutations, particularly G12D and G10, drive oncogenesis in multiple cancers. Recent patents WO 2025/054347 A1 and WO 2025/054530 A1 disclose novel small molecule inhibitors that selectively target these mutations, demonstrating high potency, favorable pharmacokinetics, and promising therapeutic potential in challenging pancreatic, lung, and colorectal cancers.
摘要
KRAS突变，尤其是G12D和G10突变，在多种癌症中驱动肿瘤发生。最近的专利WO 2025/054347 A1和WO 2025/054530 A1披露了选择性靶向这些突变的新型小分子抑制剂，在具有挑战性的胰腺癌、肺癌和结直肠癌中显示出高效力、良好的药代动力学和有前景的治疗潜力。
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本文引用的文献
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Recent Anti-KRAS Therapies: A "Possible Impossibility" for Pancreatic Ductal Adenocarcinoma.近期的抗KRAS疗法：胰腺导管腺癌的“看似不可能之事”
Cancers (Basel). 2025 Feb 19;17(4):704. doi: 10.3390/cancers17040704.
2
The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives.KRAS 突变在结直肠癌中的作用：生物学见解、临床意义及未来治疗前景
Cancers (Basel). 2025 Jan 27;17(3):428. doi: 10.3390/cancers17030428.
3
The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis.KRAS 突变的非小细胞肺癌中免疫疗法的疗效：一项系统评价和荟萃分析。
Cancer Cell Int. 2024 Nov 1;24(1):361. doi: 10.1186/s12935-024-03498-9.
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Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.白血病中RAS信号通路靶向治疗的进展与挑战
Mol Cancer Ther. 2025 Jan 2;24(1):33-46. doi: 10.1158/1535-7163.MCT-24-0504.
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The next-generation KRAS inhibitors…What comes after sotorasib and adagrasib?下一代 KRAS 抑制剂……索托拉西布和阿达格拉西布之后是什么？
Lung Cancer. 2024 Aug;194:107886. doi: 10.1016/j.lungcan.2024.107886. Epub 2024 Jul 10.
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Structural perspectives on recent breakthrough efforts toward direct drugging of RAS and acquired resistance.关于近期针对RAS直接药物治疗及获得性耐药的突破性研究成果的结构视角。
Front Oncol. 2024 May 22;14:1394702. doi: 10.3389/fonc.2024.1394702. eCollection 2024.
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