Category Archives: drug discovery news

A multipronged attack on malaria

Validation of the protein kinase PfCLK3 as a multistage cross-species malarial drug target. Targeting parasite’s protein kinase Malaria elimination goals are constantly eroded by the challenge of emerging drug and insecticide resistance. Alam et al. have taken established drug targets—CLK protein kinases involved in regulation of RNA splicing—and investigated how inhibition of the parasite’s enzymes […]

Targeting cardiac fibrosis with engineered T cells

Abstract Fibrosis is observed in nearly every form of myocardial disease1. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and […]

Orphan GPCR exhibits anti-opioid activity

Worms yield opioid receptor insight The µ-opioid receptor (MOR) is the target of pain-reducing drugs, including morphine and the potent synthetic opioid fentanyl. Better understanding of the receptor system is needed to suppress potentially deadly side effects and manage addiction potential. Wang et al. used a screen in the worm Caenorhabditis elegans to find genes […]

Drug Discovery News: ADCK3/COQ8A

UbiB kinase-like proteins exist in archaea, bacteria and eukaryotes, and comprise ~25% of all microbial protein kinase-like (PKL) enzymes. The founding member of the UbiB family, UbiB from Escherichia coli, supports the biosynthesis of ubiquinone, also known as coenzyme Q (CoQ), by an unknown mechanism. In eukaryotes, UbiB homologues are found exclusively in mitochondria, where […]

CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy

Abstract Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called ‘don’t eat me’ signals—including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 […]

A probe for every protein

Science Translational Medicine 11 Sep 2019:Vol. 11, Issue 509, eaaw8412DOI: 10.1126/scitranslmed.aaw8412 Drugs may not do what we think they do The majority of proposed anticancer treatments do not succeed in advancing to clinical use because of problems with efficacy or toxicity, often for unclear reasons. Lin et al. discovered that a drug candidate in clinical […]

The great escape: tumour cell plasticity in resistance to targeted therapy

Abstract The success of targeted therapies in cancer treatment has been impeded by various mechanisms of resistance. Besides the acquisition of resistance-conferring genetic mutations, reversible mechanisms that lead to drug tolerance have emerged. Plasticity in tumour cells drives their transformation towards a phenotypic state that no longer depends on the drug-targeted pathway. These drug-refractory cells […]

Targeting metabolic dysregulation for fibrosis therapy

Abstract Fibrosis is the abnormal deposition of extracellular matrix, which can lead to organ dysfunction, morbidity, and death. The disease burden caused by fibrosis is substantial, and there are currently no therapies that can prevent or reverse fibrosis. Metabolic alterations are increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types. […]

Pharmacological modulation of nucleic acid sensors ¡ª therapeutic potential and persisting obstacles

Abstract Nucleic acid sensors, primarily TLR and RLR family members, as well as cGAS–STING signalling, play a critical role in the preservation of cellular and organismal homeostasis. Accordingly, deregulated nucleic acid sensing contributes to the origin of a diverse range of disorders, including infectious diseases, as well as cardiovascular, autoimmune and neoplastic conditions. Accumulating evidence […]

Targeting mRNA processing as an anticancer strategy

Abstract Discoveries in the past decade have highlighted the potential of mRNA as a therapeutic target for cancer. Specifically, RNA sequencing revealed that, in addition to gene mutations, alterations in mRNA can contribute to the initiation and progression of cancer. Indeed, precursor mRNA processing, which includes the removal of introns by splicing and the formation […]