Dataset Information

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.

ABSTRACT: The discovery of the endogenous melanocortin agonists in the 1950s have resulted in sixty years of melanocortin ligand research. Early efforts involved truncations or select modifications of the naturally occurring agonists leading to the development of many potent and selective ligands. With the identification and cloning of the five known melanocortin receptors, many ligands were improved upon through bench-top in vitro assays. Optimization of select properties resulted in ligands adopted as clinical candidates. A summary of every melanocortin ligand is outside the scope of this review. Instead, this review will focus on the following topics: classic melanocortin ligands, selective ligands, small molecule (non-peptide) ligands, ligands with sex-specific effects, bivalent and multivalent ligands, and ligands advanced to clinical trials. Each topic area will be summarized with current references to update the melanocortin field on recent progress. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.

SUBMITTER: Ericson MD

PROVIDER: S-EPMC5600687 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.

Ericson Mark D MD Lensing Cody J CJ Fleming Katlyn A KA Schlasner Katherine N KN Doering Skye R SR Haskell-Luevano Carrie C

Biochimica et biophysica acta. Molecular basis of disease 20170329 10 Pt A

The discovery of the endogenous melanocortin agonists in the 1950s have resulted in sixty years of melanocortin ligand research. Early efforts involved truncations or select modifications of the naturally occurring agonists leading to the development of many potent and selective ligands. With the identification and cloning of the five known melanocortin receptors, many ligands were improved upon through bench-top in vitro assays. Optimization of select properties resulted in ligands adopted as c ...[more]

PMID: 28363699

Similar Datasets

Project description:BackgroundMolecular genetic testing is recommended for diagnosis of inherited cardiac disease, to guide prognosis and treatment, but access is often limited by cost and availability. Recently introduced high-throughput bench-top DNA sequencing platforms have the potential to overcome these limitations.Methodology/principal findingsWe evaluated two next-generation sequencing (NGS) platforms for molecular diagnostics. The protein-coding regions of six genes associated with inherited arrhythmia syndromes were amplified from 15 human samples using parallelised multiplex PCR (Access Array, Fluidigm), and sequenced on the MiSeq (Illumina) and Ion Torrent PGM (Life Technologies). Overall, 97.9% of the target was sequenced adequately for variant calling on the MiSeq, and 96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and most were problematic for both platforms. Variant calling was assessed using 107 variants detected using Sanger sequencing: within adequately sequenced regions, variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%, PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%). At the time of the study the Ion Torrent PGM had a lower capital cost and individual runs were cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs), with reduced hands-on time and simpler laboratory workflows. Both provide significant cost and time savings over conventional methods, even allowing for adjunct Sanger sequencing to validate findings and sequence exons missed by NGS.Conclusions/significanceMiSeq and Ion Torrent PGM both provide accurate variant detection as part of a PCR-based molecular diagnostic workflow, and provide alternative platforms for molecular diagnosis of inherited cardiac conditions. Though there were performance differences at this throughput, platforms differed primarily in terms of cost, scalability, protocol stability and ease of use. Compared with current molecular genetic diagnostic tests for inherited cardiac arrhythmias, these NGS approaches are faster, less expensive, and yet more comprehensive.

Project description:BackgroundThe assessment of spinal stiffness by manual palpation in clinical settings has demonstrated both poor accuracy and reliability. More recently, mechanical methods for assessment of spinal stiffness have demonstrated superior accuracy and reliability. However, mechanical methods of spinal stiffness assessment can be expensive, time consuming and/or unsuited to clinical practice. While a new device has been designed to address these issues (VerteTrack), its benchtop performance remains unknown.AimTo measure the bench-top performance of VerteTrack.MethodsA series of laboratory-based experiments were conducted in February 2018 to investigate the accuracy (precision and bias) of load and displacement measurements obtained by VerteTrack and then were compared against an appropriate reference standard. Measurements of both multiple-level continuous assessment (multiple spinal levels measured), and single-level assessment (single spinal level measured) were performed on a viscoelastic foam medium (AIREX® balance beam, Switzerland) and the resulting stiffness calculated.ResultsVerteTrack demonstrated high precision at all loads and displacements. There was minimal systematic measurement bias identified for applied versus reference load (mean bias = - 0.123 N; 95%CI - 0.182 to 0.428 N, p < .001), and no systematic measurement bias for measured versus reference displacement (mean difference = 0.02 mm; 95%CI - 0.09 to 0.14 mm, p < .001). The magnitude of stiffness obtained during multiple-level continuous assessment was on average 0.25 N/mm (2.79%) less than that for single-level assessment (95%CI - 0.67 to 0.17 N/mm, p < .001).ConclusionsVerteTrack demonstrated high accuracy (high precision, low bias) under bench-top conditions. The difference in stiffness found between multiple versus single spinal levels should be considered in the research context, but is unlikely to be clinically relevant. The results of this study demonstrate that VerteTrack may be suitable for both single and multi-level spinal stiffness measurements in-vivo.

Dataset Information

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.

Publications

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets