CVM-1118（foslinanib）作用机制相关数据表（DataSheet5）

数据集获取（Figshare）

• 源站标题：DataSheet5_CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.PDF
• DOI：10.3389/pore.2023.1611038.s005
• 发布日期：2023-06-07
• 文件数：1 个
• 文件总体积：183.57 KB
• 源站页面：https://frontiersin.figshare.com/articles/dataset/DataSheet5_CVM-1118_foslinanib_a_2-phenyl-4-quinolone_derivative_promotes_apoptosis_and_inhibits_vasculogenic_mimicry_via_targeting_TRAP1_PDF/23310356

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curl -L -o "DataSheet5_CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.PDF" "https://ndownloader.figshare.com/files/41098637"

文件清单

• DataSheet5_CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1.PDF（183.57 KB）

文件总体积 183.57 KB（源站 API 实测）。

数据说明

CVM-1118 (foslinanib) is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The NCI 60 cancer panel screening showed CVM-1125, the major active metabolite of CVM-1118, to exhibit growth inhibitory and cytotoxic effects at nanomolar range. CVM-1118 possesses multiple bioactivities, including inducing cellular apoptosis, cell cycle arrest at G2/M, as well as inhibiting vasculogenic mimicry (VM) formation. The TNF receptor associated protein 1 (TRAP1) was identified as the binding target of CVM-1125 using nematic protein organization technique (NPOT) interactome analysis. Further studies demonstrated CVM-1125 reduced the protein level of TRAP1 and impeded its downstream signaling by reduction of cellular succinate levels and destabilization of HIF-1α. The pharmacogenomic biomarkers associated with CVM-1118 were also examined by Whole Genome CRISPR Knock-Out Screening. Two hits (STK11 and NF2) were confirmed with higher sensitivity to the drug in cell knock-down experiments. Biological assays indicate that the mechanism of action of CVM-1118 is via targeting TRAP1 to induce mitochondrial apoptosis, suppress tumor cell growth, and inhibit vasculogenic mimicry formation. Most importantly, the loss-of-function mutations of STK11 and NF2 are potential biomarkers of CVM-1118 which can be applied in the selection of cancer patients for CVM-1118 treatment. CVM-1118 is currently in its Phase 2a clinical development.

许可

CC BY 4.0

引用

学术使用请引用 DOI 10.3389/pore.2023.1611038.s005（source: https://frontiersin.figshare.com/articles/dataset/DataSheet5_CVM-1118_foslinanib_a_2-phenyl-4-quinolone_derivative_promotes_apoptosis_and_inhibits_vasculogenic_mimicry_via_targeting_TRAP1_PDF/23310356）。