Guanabenz acetate induces endoplasmic reticulum stress-related cell death in hepatocellular carcinoma cells

Journal of Pathology and Translational Medicine

Kang HJ, Seol HS, Lee SE, Suh YA, Kim J, Jang SJ, Yu E
Journal of Pathology and Translational Medicine - vol. 53 94-103 (2019)

Background: Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. Methods: Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 […]

First-in-class allosteric inhibitors of bacterial IMPDHs

European Journal of Medicinal Chemistry

Alexandre T, Lupan A, Helynck O, Vichier-Guerre S, Dugué L, Gelin M, Haouz A, Labesse G, Munier-Lehmann H
European Journal of Medicinal Chemistry - vol. 167 124-132 (2019)

Inosine-5‘-monophosphate dehydrogenase (IMPDH) is an essential enzyme in many bacterial pathogens and is considered as a potential drug target for the development of new antibacterial agents. Our recent work has revealed the crucial role of one of the two structural domains (i.e. Bateman domain) in the regulation of the quaternary structure and enzymatic activity of […]

Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies

Molecular Cell

Campos AI, Zampieri M
Molecular Cell - vol. 74 1291-1303.e6 (2019)

Alternative to the conventional search for single-target, single-compound treatments, combination therapies can open entirely new opportunities to fight antibiotic resistance. However, combinatorial complexity prohibits experimental testing of drug combinations on a large scale, and methods to rationally design combination therapies are lagging behind. Here, we developed a combined experimental-computational approach to predict drug-drug interactions using […]

Identification of Off-Patent Compounds That Present Antifungal Activity against the Emerging Fungal Pathogen Candida auris

Frontiers in Cellular and Infection Microbiology

De Oliveira HC, Monteiro MC, Rossi SA, Pemán J, Ruiz-Gaitán A, Mendes-Giannini MJS, Mellado E, Zaragoza O
Frontiers in Cellular and Infection Microbiology - vol. 9 1-10 (2019)

Candida auris is an emerging fungal pathogen of great concern among the scientific community because it is causing an increasing number of hospital outbreaks of difficult management worldwide. In addition, isolates from this species frequently present reduced susceptibility to azole and echinocandin drugs. For this reason, it is necessary to develop new antifungal strategies to […]

Chlorambucil targets BRCA 1/2‐deficient tumours and counteracts PARP inhibitor resistance

EMBO Molecular Medicine

Tacconi EM, Badie S, De Gregoriis G, Reisländer T, Lai X, Porru M, Folio C, Moore J, Kopp A, Baguña Torres J, Sneddon D, Green M, Dedic S, Lee JW, Batra AS, Rueda OM, Bruna A, Leonetti C, Caldas C, Cornelissen B, Brino L, Ryan A, Biroccio A, Tarsounas M
EMBO Molecular Medicine - vol. 11 1-16 (2019)

© 2019 The Authors. Published under the terms of the CC BY 4.0 license Due to compromised homologous recombination (HR) repair, BRCA1- and BRCA2-mutated tumours accumulate DNA damage and genomic rearrangements conducive of tumour progression. To identify drugs that target specifically BRCA2-deficient cells, we screened a chemical library containing compounds in clinical use. The top […]

The 2019 Garrod Lecture: MDR efflux in Gram-negative bacteria – How understanding resistance led to a new tool for drug discovery

Journal of Antimicrobial Chemotherapy

Piddock LJ
Journal of Antimicrobial Chemotherapy - vol. 74 3128-3134 (2019)

The AcrAB-TolC MDR efflux system confers intrinsic MDR and overproduction confers clinically relevant resistance to some antibiotics active against Gram-negative bacteria. The system is made up of three components, namely AcrA, AcrB and TolC, otherwise known as the AcrAB-TolC tripartite system. Inactivation or deletion of a gene encoding one of the constituent proteins, or substitution […]

Repurposing of ribavirin as an adjunct therapy against invasive Candida strains in an in vitro study

Antimicrobial Agents and Chemotherapy

Yousfi H, Cassagne C, Ranque S, Rolain JM, Bittar F
Antimicrobial Agents and Chemotherapy - vol. 63 1-8 (2019)

The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy […]

A Small Molecule Targeting Mutagenic Translesion


Wojtaszek JL, Chatterjee N, Najeeb J, Hong J, Walker GC, Zhou P
Cell - vol. 178 152-159.e11 (2019)

Extensive impact of non-antibiotic drugs on human gut bacteria


Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, Patil KR, Bork P, Typas A
Nature - vol. 555 623-628 (2018)

A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited […]

Screening for biologically annotated drugs that trigger triacylglycerol accumulation in the diatom Phaeodactylum

Plant Physiology

Melissa Conte JL
Plant Physiology 532-552 (2018)