POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative
Descrição
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.
![POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative](https://www.researchgate.net/publication/348885218/figure/tbl1/AS:996408245121024@1614573646472/Most-frequently-comutated-genes-with-STK11-in-non-small-cell-lung-cancer-according-to.png)
Most frequently comutated genes with STK11 in non-small cell lung
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Frontiers The development of cancers research based on mitochondrial heat shock protein 90
![POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative](https://www.researchgate.net/publication/237093524/figure/fig5/AS:668498447589376@1536393858017/TRAP1-Knockdown-Inhibits-In-Vitro-and-In-Vivo-Neoplastic-Transformation-A-and-B-Human.png)
TRAP1 Knockdown Inhibits In Vitro and In Vivo Neoplastic Transformation
![POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative](https://www.por-journal.com/files/Articles/1611038/pore-29-1611038-HTML-r2/image_m/pore-29-1611038-g007.jpg)
POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1
![POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative](https://www.por-journal.com/files/Articles/1610980/pore-29-1610980-HTML/image_m/pore-29-1610980-t001.jpg)
POR Tumor subtypes and signature model construction based on chromatin regulators for better prediction of prognosis in uveal melanoma
Foslinanib, C16H13FNO6P
Foslinanib, C16H13FNO6P
![POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative](https://www.researchgate.net/publication/260253948/figure/fig1/AS:601803070660613@1520492441191/HIF-1a-is-required-for-the-growth-and-survival-of-LKB1-deficient-cells-in-response-to.png)
HIF-1α is required for the growth and survival of LKB1-deficient cells
![POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative](https://www.por-journal.com/files/Articles/1611038/pore-29-1611038-HTML-r2/image_m/pore-29-1611038-g005.jpg)
POR CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1
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