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临床和口服兼容的制剂生产的靶向DDX5(p68)的分子胶FL118产品对人类癌症显示出低毒性但高效能。

Clinically and orally compatible formulation-manufactured DDX5 (p68)-targeting molecular glue FL118 products exhibit low toxicity but high efficacy against human cancer.

作者信息

Ling Xiang, Wu Wenjie, Yan Li, Curtin Leslie, Farrauto Melanie M, Sexton Sandra, Jamroze Anmbreen, Yu Changjun, Fountzilas Christos, Tang Dean G, Li Fengzhi

机构信息

Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, 14263, USA.

Canget BioTekpharma LLC, Buffalo, New York, 14203, USA.

出版信息

J Pharm Anal. 2024 Nov;14(11):101001. doi: 10.1016/j.jpha.2024.101001. Epub 2024 May 13.

DOI:10.1016/j.jpha.2024.101001
PMID:39759975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696646/
Abstract

Image 1.

摘要

图1。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1583/11696646/880ed43f7845/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1583/11696646/8977ce338723/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1583/11696646/880ed43f7845/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1583/11696646/8977ce338723/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1583/11696646/880ed43f7845/gr1.jpg

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Clinically and orally compatible formulation-manufactured DDX5 (p68)-targeting molecular glue FL118 products exhibit low toxicity but high efficacy against human cancer.临床和口服兼容的制剂生产的靶向DDX5(p68)的分子胶FL118产品对人类癌症显示出低毒性但高效能。
J Pharm Anal. 2024 Nov;14(11):101001. doi: 10.1016/j.jpha.2024.101001. Epub 2024 May 13.
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An intravenous (i.v.) route-compatible formulation of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, improves FL118 antitumor efficacy and therapeutic index (TI).一种静脉(i.v.)途径兼容的 FL118 制剂,一种存活素、Mcl-1、XIAP 和 cIAP2 选择性抑制剂,可提高 FL118 的抗肿瘤疗效和治疗指数(TI)。
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Role of DEAD/DEAH-box helicases in immunity, infection and cancers.DEAD/DEAH盒解旋酶在免疫、感染和癌症中的作用。
Cell Commun Signal. 2025 Jun 19;23(1):292. doi: 10.1186/s12964-025-02225-9.

本文引用的文献

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Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence.DEAD-box RNA 解旋酶 DDX5(p68)在癌症 DNA 修复、免疫抑制、癌症代谢控制、病毒感染促进以及对人类微生物组(微生物群)的负面影响中的作用。
J Exp Clin Cancer Res. 2023 Aug 19;42(1):213. doi: 10.1186/s13046-023-02787-x.
2
DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer.靶向 DDX5 mRNA 的反义寡核苷酸作为一种新的治疗方法,有望用于治疗去势抵抗性前列腺癌。
Mol Ther. 2023 Feb 1;31(2):471-486. doi: 10.1016/j.ymthe.2022.08.005. Epub 2022 Aug 13.
3
Molecular Glues: Capable Protein-Binding Small Molecules That Can Change Protein-Protein Interactions and Interactomes for the Potential Treatment of Human Cancer and Neurodegenerative Diseases.
分子胶:能够结合蛋白质的小分子,可改变蛋白质-蛋白质相互作用和蛋白质组,从而有潜力治疗人类癌症和神经退行性疾病。
Int J Mol Sci. 2022 Jun 1;23(11):6206. doi: 10.3390/ijms23116206.
4
FL118, acting as a 'molecular glue degrader', binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c-Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy.FL118 作为一种“分子胶水降解剂”,能结合去磷酸化并降解癌蛋白 DDX5(p68),从而高效控制结直肠癌和胰腺癌中的 c-Myc、存活素和突变型 Kras。
Clin Transl Med. 2022 May;12(5):e881. doi: 10.1002/ctm2.881.
5
Retraction: DEAD-Box Helicase 5 Interacts With Transcription Factor 12 and Promotes the Progression of Osteosarcoma by Stimulating Cell Cycle Progression.撤回声明:DEAD盒解旋酶5与转录因子12相互作用并通过刺激细胞周期进程促进骨肉瘤进展。
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An ABCG2 non-substrate anticancer agent FL118 targets drug-resistant cancer stem-like cells and overcomes treatment resistance of human pancreatic cancer.一种非 ABCG2 底物的抗癌剂 FL118 靶向耐药性癌症干细胞样细胞,并克服了人胰腺癌细胞的治疗抵抗性。
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