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DRUG:

VS-5584

i
Other names: SB2343, VS-5584, VS 5584
Associations
Trials
Company:
Verastem
Drug class:
mTOR inhibitor, PI3K inhibitor
Related drugs:
Associations
Trials
1year
PI3K/mTOR inhibitor VS-5584 combined with PLK1 inhibitor exhibits synergistic anti-cancer effects on non-small cell lung cancer. (PubMed, Eur J Pharmacol)
The use of the ROS inhibitor N-acetylcysteine (NAC) effectively reduced ROS levels and decreased the proportion of apoptotic cells. VS-5584 combined with NMS-P937 exhibited a synergistic effect in inhibiting NSCLC cell growth. These findings suggest that VS-5584 has potential as a therapeutic strategy for treating NSCLC.
Journal
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CASP3 (Caspase 3) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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onvansertib (PCM-075) • VS-5584
over1year
Preclinical • Journal • Epigenetic controller
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sirolimus • fimepinostat (CUDC-907) • BGT226 • VS-5584
over1year
SIRT2 inhibitor SirReal2 enhances anti-tumor effects of PI3K/mTOR inhibitor VS-5584 on acute myeloid leukemia cells. (PubMed, Cancer Med)
Taken together, the PI3K/mTOR inhibitor VS-5584 was effective in suppressing AML cell proliferation. PI3K/mTOR inhibitor combined with SIRT2 inhibitor exhibited a synergistic inhibitory effect on AML cells. Our findings offer promising therapeutic strategies and drug candidates for the treatment of AML.
Journal
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VS-5584
over1year
The lncRNA expression profile signature of leukemia stem cells is altered upon PI3K/mTOR inhibition: an in vitro and in silico study. (PubMed, Nucleosides Nucleotides Nucleic Acids)
We suppressed PI3K/Akt/mTOR signaling in LSC and HSC cell-lines by specific PI3K/mTOR dual-inhibitor (VS-5584) and confirmed the inhibition by antibody-array...SRA was predicted to interact with CREB1, RARA, and PPARA. The possible DELs' targets were predicted to form six ontological groups, be highly enriched for phosphoprotein, and be involved in "PPAR signaling pathway" and "ChREBP regulation by carbohydrates and cAMP." These results will help to elucidate the roles of lncRNAs in the mechanisms that provide selective advantages to leukemia stem cells.
Preclinical • Journal
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CEBPA (CCAAT Enhancer Binding Protein Alpha) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • CREB1 (CAMP Responsive Element Binding Protein 1) • NANOG (Nanog Homeobox) • SNHG5 (Small Nucleolar RNA Host Gene 5) • ZEB2 (Zinc Finger E-Box Binding Homeobox 2) • PPARA (Peroxisome Proliferator Activated Receptor Alpha) • RELA (RELA Proto-Oncogene)
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VS-5584
over3years
PI3K/mTOR dual-inhibition with VS-5584 enhances anti-leukemic efficacy of ponatinib in blasts and Ph-negative LSCs of chronic myeloid leukemia. (PubMed, Eur J Pharmacol)
Transcriptional regulation resulted in alterations in the expression levels of target mRNAs. Our results highlight PoVS can be a promising treatment strategy for eliminating CML cells and LSCs selectively, with the reduced ponatinib doses.
Clinical • Journal
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STAT3 (Signal Transducer And Activator Of Transcription 3) • AKT1S1 (AKT1 Substrate 1)
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Iclusig (ponatinib) • VS-5584
4years
VS-5584, a PI3K/mTOR dual inhibitor, exerts antitumor effects on neuroblastomas in vitro and in vivo. (PubMed, J Pediatr Surg)
VS-5584 blocks the PI3K/mTOR pathway, induces a G0/G1 cell cycle arrest, and exerts antitumor effects on neuroblastomas both in vitro and in vivo.
Preclinical • Journal
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CCNE1 (Cyclin E1) • CDK2 (Cyclin-dependent kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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CDKN1B expression
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VS-5584
over4years
CCT128930 induces G1-phase arrest and apoptosis and synergistically enhances the anticancer efficiency of VS5584 in human osteosarcoma cells. (PubMed, Biomed Pharmacother)
Moreover, CCT128930 treatment obviously enhanced VS5584-induced growth inhibition and apoptosis in human osteosarcoma cells, followed by enhanced PARP cleavage and caspase-3 activation. Taken together, CCT128930 alone or combined treatment with CCT128930 and VS5584 both effectively inhibited human osteosarcoma cells growth by induction of G1-phase arrest and apoptosis through regulating PI3K/mTOR and MAPKs pathways.
Journal • PARP Biomarker
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CCND1 (Cyclin D1) • CASP3 (Caspase 3) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1)
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CCT128930 • VS-5584
over4years
VS-5584 Inhibits Human Osteosarcoma Cells Growth by Induction of G1-phase Arrest through Regulating PI3K/mTOR and MAPK Pathways. (PubMed, Curr Cancer Drug Targets)
Our findings validated that VS-5584 may be a promising anticancer agent with potential application in the chemotherapy and chemoprevention of human osteosarcoma.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1)
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VS-5584