New Drug Repositioning Candidates for T-ALL Identified Via Human/Murine Gene Signature Comparison

Bonnet, Raphaël; Nebout, Marielle; Brousse, Carine; Reinier, Frédéric; Imbert, Véronique; Röhrlich, Pierre; Peyron, Jean‐François

doi:10.3389/fonc.2020.557643

Cited by 7 publications

(1 citation statement)

References 39 publications

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“…The Connectivity Map (Map) developed by the Broad Institute has been used to identify drugs with the potential to interfere with diverse pathological situations such as epilepsy [ 18 ], pulmonary arterial hypertension [ 19 ], asthma [ 20 ]. Based on cancer GEPs, several molecules have been identified in silico and showed promising properties in vitro / in vivo in a variety of cancers such as renal cancer [ 21 ], colorectal cancer [ 22 ], bladder cancer [ 23 ], leukemia [ 24 ], neuroblastoma [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potentially anti-COVID-19 active drugs using the connectivity MAP

2022

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Drug repurposing can be an interesting strategy for an emergency response to the severe acute respiratory syndrome-coronavirus-2, (SARS-COV-2), the causing agent of the coronavirus disease-19 (COVID-19) pandemic. For this, we applied the Connectivity Map (CMap) bioinformatic resource to identify drugs that generate, in the CMap database, gene expression profiles (GEP) that negatively correlate with a SARS-COV-2 GEP, anticipating that these drugs could antagonize the deleterious effects of the virus at cell, tissue or organism levels. We identified several anti-cancer compounds that target MDM2 in the p53 pathway or signaling proteins: Ras, PKBβ, Nitric Oxide synthase, Rho kinase, all involved in the transmission of proliferative and growth signals. We hypothesized that these drugs could interfere with the high rate of biomass synthesis in infected cells, a feature shared with cancer cells. Other compounds including etomoxir, triacsin-c, PTB1-IN-3, are known to modulate lipid metabolism or to favor catabolic reactions by activating AMPK. Four different anti-inflammatory molecules, including dexamethasone, fluorometholone and cytosporone-b, targeting the glucocorticoid receptor, cyclooxygenase, or NUR77 also came out of the analysis. These results represent a first step in the characterization of potential repositioning strategies to treat SARS-COV-2.

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Section: Discussionmentioning

confidence: 99%

Identification of potentially anti-COVID-19 active drugs using the connectivity MAP

2022

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Integrated systems biology analysis of acute lymphoblastic leukemia: unveiling molecular signatures and drug repurposing opportunities

Budak,

Tükel,

Turanlı

et al. 2024

Ann Hematol

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Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by aberrant proliferation and accumulation of lymphoid precursor cells within the bone marrow. The tyrosine kinase inhibitor (TKI), imatinib mesylate, has played a significant role in the treatment of Philadelphia chromosome-positive ALL (Ph + ALL). However, the achievement of durable and sustained therapeutic success remains a challenge due to the development of TKI resistance during the clinical course.The primary objective of this investigation is to propose a novel and efficacious treatment approach through drug repositioning, targeting ALL and its Ph + subtype by identifying and addressing differentially expressed genes (DEGs). This study involves a comprehensive analysis of transcriptome datasets pertaining to ALL and Ph + ALL in order to identify DEGs associated with the progression of these diseases to identify possible repurposable drugs that target identified hub proteins.The outcomes of this research have unveiled 698 disease-related DEGs for ALL and 100 for Ph + ALL. Furthermore, a subset of drugs, specifically glipizide for Ph + ALL, and maytansine and isoprenaline for ALL, have been identified as potential candidates for therapeutic intervention. Subsequently, cytotoxicity assessments were performed to confirm the in vitro cytotoxic effects of these selected drugs on both ALL and Ph + ALL cell lines.In conclusion, this study offers a promising avenue for the management of ALL and Ph + ALL through drug repurposed drugs. Further investigations are necessary to elucidate the mechanisms underlying cell death, and clinical trials are recommended to validate the promising results obtained through drug repositioning strategies.

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In vitro synergistic antiviral activity of repurposed drugs against enterovirus 71

Jitobaom,

Boonarkart,

Thongon

et al. 2024

Arch Virol

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New Drug Repositioning Candidates for T-ALL Identified Via Human/Murine Gene Signature Comparison

Cited by 7 publications

References 39 publications

Identification of potentially anti-COVID-19 active drugs using the connectivity MAP

Identification of potentially anti-COVID-19 active drugs using the connectivity MAP

Integrated systems biology analysis of acute lymphoblastic leukemia: unveiling molecular signatures and drug repurposing opportunities

In vitro synergistic antiviral activity of repurposed drugs against enterovirus 71

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