靶向KRAS突变：发现用于潜在治疗难治性癌症的小分子抑制剂。
Targeting KRAS Mutations: Discovery of Small Molecule Inhibitors for the Potential Treatment of Intractable Cancers.
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. 2023 Jul 11;14(8):1041-1042. doi: 10.1021/acsmedchemlett.3c00277. eCollection 2023 Aug 10.
Abstract
The KRAS mutation, frequently found in pancreatic cancer, is representative of various challenging cancers and is a crucial target for chemotherapy drug development. Researchers are exploring highly selective and potent small molecule inhibitors of KRAS to meet the needs of patients with this mutation. The Patent Highlight reveals novel compounds capable of inhibiting KRAS proteins, potentially useful in treating KRAS-associated diseases, including cancers.
摘要
KRAS 突变在胰腺癌中经常出现，是各类具有挑战性的癌症的代表，也是化疗药物研发的关键靶点。研究人员正在探索高度选择性和强效的 KRAS 小分子抑制剂，以满足患有这种突变的患者的需求。专利亮点揭示了能够抑制 KRAS 蛋白的新型化合物，可能对治疗包括癌症在内的 KRAS 相关疾病有用。
相似文献
1
Targeting KRAS Mutations: Discovery of Small Molecule Inhibitors for the Potential Treatment of Intractable Cancers.靶向KRAS突变：发现用于潜在治疗难治性癌症的小分子抑制剂。
ACS Med Chem Lett. 2023 Jul 11;14(8):1041-1042. doi: 10.1021/acsmedchemlett.3c00277. eCollection 2023 Aug 10.
2
Design, synthesis, and evaluation of purine and pyrimidine-based G12D inhibitors: Towards potential anticancer therapy.基于嘌呤和嘧啶的G12D抑制剂的设计、合成与评估：迈向潜在的抗癌治疗
Heliyon. 2024 Apr 2;10(7):e28495. doi: 10.1016/j.heliyon.2024.e28495. eCollection 2024 Apr 15.
3
Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.探索 KRAS(G12D)的变构开关 II 口袋构象与突变体选择性单域抗体抑制剂。
Proc Natl Acad Sci U S A. 2023 Jul 11;120(28):e2302485120. doi: 10.1073/pnas.2302485120. Epub 2023 Jul 3.
4
Unveiling New KRAS Inhibitors: A Promising Approach for Pancreatic Cancer Therapy.揭示新型KRAS抑制剂：胰腺癌治疗的一种有前景的方法。
ACS Med Chem Lett. 2023 Jun 9;14(7):889-890. doi: 10.1021/acsmedchemlett.3c00222. eCollection 2023 Jul 13.
5
Next batter up! Targeting cancers with KRAS-G12D mutations.下一位击球手就位！靶向KRAS-G12D突变的癌症。
Trends Cancer. 2023 Nov;9(11):955-967. doi: 10.1016/j.trecan.2023.07.010. Epub 2023 Aug 15.
6
Discovery of Selective and Potent KRAS Inhibitors as Potential Therapy in Cancer.发现选择性强效KRAS抑制剂作为癌症的潜在治疗方法。
ACS Med Chem Lett. 2023 May 10;14(6):689-691. doi: 10.1021/acsmedchemlett.3c00167. eCollection 2023 Jun 8.
7
KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge.KRAS（G12D）可通过形成盐桥被强效抑制剂靶向。
Cell Discov. 2022 Jan 25;8(1):5. doi: 10.1038/s41421-021-00368-w.
8
The suppressive efficacy of THZ1 depends on KRAS mutation subtype and is associated with super-enhancer activity and the PI3K/AKT/mTOR signalling in pancreatic ductal adenocarcinoma: A hypothesis-generating study.THZ1 的抑制功效取决于 KRAS 突变亚型，并与胰腺导管腺癌中的超级增强子活性和 PI3K/AKT/mTOR 信号通路相关：一项生成假说的研究。
Clin Transl Med. 2023 Dec;13(12):e1500. doi: 10.1002/ctm2.1500.
9
Identification of Dietary Bioflavonoids as Potential Inhibitors against KRAS G12D Mutant-Novel Insights from Computer-Aided Drug Discovery.鉴定膳食生物类黄酮作为KRAS G12D突变体的潜在抑制剂——计算机辅助药物发现的新见解
Curr Issues Mol Biol. 2023 Mar 6;45(3):2136-2156. doi: 10.3390/cimb45030137.
10
Inhibition of GTPase KRAS: a review of patent literature.KRAS GTPase 抑制：专利文献综述。
Expert Opin Ther Pat. 2024 Aug;34(8):701-721. doi: 10.1080/13543776.2024.2369630. Epub 2024 Jun 26.
引用本文的文献
1
In Silico Prediction of New Inhibitors for Kirsten Rat Sarcoma G12D Cancer Drug Target Using Machine Learning-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulation Approaches.使用基于机器学习的虚拟筛选、分子对接和分子动力学模拟方法对 Kirsten 大鼠肉瘤 G12D 癌症药物靶点新抑制剂进行计算机模拟预测。
Pharmaceuticals (Basel). 2024 Apr 25;17(5):551. doi: 10.3390/ph17050551.
本文引用的文献
1
Targeting the 'Undruggable' Driver Protein, KRAS, in Epithelial Cancers: Current Perspective.针对上皮性癌症中的“不可成药”驱动蛋白 KRAS：当前视角。
Cells. 2023 Feb 15;12(4):631. doi: 10.3390/cells12040631.
2
KRAS G12D mutation in Brunner gland adenoma.布伦纳腺腺瘤中的KRAS G12D突变
BMJ Case Rep. 2023 Jan 27;16(1):e252160. doi: 10.1136/bcr-2022-252160.
3
KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?针对胰腺癌的KRAS G12D靶向疗法：堡垒已被攻克了吗？
Front Oncol. 2022 Nov 29;12:1013902. doi: 10.3389/fonc.2022.1013902. eCollection 2022.
4
Targeting KRAS in PDAC: A New Way to Cure It?在胰腺癌中靶向KRAS：一种新的治愈方法？
Cancers (Basel). 2022 Oct 11;14(20):4982. doi: 10.3390/cancers14204982.
5
G12D Mutation Subtype in Pancreatic Ductal Adenocarcinoma: Does It Influence Prognosis or Stage of Disease at Presentation?胰腺导管腺癌中的 G12D 突变亚型：它是否影响预后或疾病的分期？
Cells. 2022 Oct 10;11(19):3175. doi: 10.3390/cells11193175.
6
Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants.通过靶向所有 KRAS 突变体来拓展精准肿瘤学的应用范围。
Cancer Discov. 2022 Apr 1;12(4):924-937. doi: 10.1158/2159-8290.CD-21-1331.
Zotero 插件