Drug target miRNAs: chances and challenges

Schmidt, Marco F.

doi:10.1016/j.tibtech.2014.09.002

Cited by 124 publications

(102 citation statements)

References 43 publications

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“…This phenotype is character ized by upregulated expression of co-inhibitory molecules such as PDL1 and ICOS ligand; the release of the anti inflammatory cytokines IL10 and TGFβ; the secretion of PCNAassociated factor, PGE 2 and cAMP 81,[114][115][116] ; and the inhibition of the release of proinflammatory cytokines including TNF, GMCSF, IL1β, IL12 and IL18 (REFS 25,(59)(60)(61). Macrophages that have ingested apoptotic cells also release proresolving lipid medi ators such as RvE1, protectin D1 and maresins 101,117 , contributing to termination of the inflammatory process.…”

Section: Macrophage Plasticitymentioning

confidence: 99%

Resolution of inflammation: a new therapeutic frontier

Fullerton

Gilroy

2016

Nat Rev Drug Discov

712

593

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Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes - a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field.

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Section: Macrophage Plasticitymentioning

confidence: 99%

Resolution of inflammation: a new therapeutic frontier

Fullerton

Gilroy

2016

Nat Rev Drug Discov

712

593

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“…5 , right). Further investigation showed that this inhibitor [ 7 ] with permission selectively reduced 90% of miRNA-96 expression level at a concentration of 40 μM in cellular assays. In conclusion, the more complex pre-miRNA offers a way to target specifi cally a single miRNA of interest with a small-molecule ligand.…”

Section: Small-molecule Mirna Modulators Identifi Ed In Cellular Screensmentioning

confidence: 99%

“…Until now, there is no standard protocol for the development of miRNA modulators as reported for protein targets [ 7 ]. The most reasonable strategy in miRNA drug discovery is the use of antisense agents [ 8 ].…”

Section: Strategies In Mirna Drug Discoverymentioning

confidence: 99%

“…Hepatitis C virus is either protected by AGO2 in the absence of Miravirsen ( left ) or allowed to degrade in its presence ( right ). Figure from [ 7 ] with permission the miR-122-AGO complex, thereby, inhibiting the essential interaction with HCV RNA for viral replication [ 21 ]. Nevertheless, Miravirsen is an exception in miRNA drug discovery.…”

Section: Fig 2 Overview Of Chemical Modifi Cations Used For the Desimentioning

confidence: 99%

“…Thus, only the blockage of the substrate binding to miR-NA's seed region should inhibit the gene silencing. [ 7 ] with permission Indeed, as one of the fi rst Kauppinen and co-workers from Santaris Pharma A/S (now F. Hoffmann-La Roche AG) demonstrated that short, octamer LNAs , so-called ' tiny LNAs ', blocking only miRNA's seed region, inhibit miRNA function totally (Fig. 6c ) [ 55 ].…”

Section: Small-molecule Mirna Modulators Identifi Ed In Cellular Screensmentioning

confidence: 99%

See 2 more Smart Citations

miRNA Targeting Drugs: The Next Blockbusters?

Schmidt

2016

Methods in Molecular Biology

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Only 20 years after the discovery of small non-coding, single-stranded ribonucleic acids, so-called microRNAs (miRNAs), as post-transcriptional gene regulators, the first miRNA-targeting drug Miravirsen for the treatment of hepatitis C has been successfully tested in clinical Phase II trials. Addressing miRNAs as drug targets may enable the cure, or at least the treatment of diseases, which presently seems impossible. However, due to miRNAs' chemical structure, generation of potential drug molecules with necessary pharmacokinetic properties is still challenging and requires a re-thinking of the drug discovery process. Therefore, this chapter highlights the potential of miRNAs as drug targets, discusses the challenges, and tries to give a complete overview of recent strategies in miRNA drug discovery.

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Drug Design of “Undruggable” Targets

Wang

2019

Chin. J. Chem.

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Drug innovation is not only reflected in the discovery of new chemotypes of active compounds against existing targets but also more dependent on the innovation of drug targets. Currently, a number of attractive and validated targets could not be targeted pharmacologically. Some have been described as “undruggable”. In this review, we summarized the current situation of “undruggable” targets, and the design strategies for “undruggable” targets, hoping to provide references for the development of innovative drugs.

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Drug target miRNAs: chances and challenges

Cited by 124 publications

References 43 publications

Resolution of inflammation: a new therapeutic frontier

Resolution of inflammation: a new therapeutic frontier

miRNA Targeting Drugs: The Next Blockbusters?

Drug Design of “Undruggable” Targets

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