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Themed collection New Talent

37 items
Editorial

Focus on new talent

MedChemComm profiles the contributors to the New Talent themed issue

Graphical abstract: Focus on new talent
From the themed collection: New Talent
Review Article

On the origins of drug polypharmacology

The ability of many drugs, unintended most often, to interact with multiple proteins is commonly referred to as polypharmacology. Could this be a reminiscent chemical signature of early protein evolution?

Graphical abstract: On the origins of drug polypharmacology
From the themed collection: MedChemComm 2013 review articles
Review Article

Small molecules aimed at type III secretion systems to inhibit bacterial virulence

The development of new anti-bacterial compounds presents a major challenge to modern medicine as bacterial strains resistant to traditional antibiotics are constantly emerging.

Graphical abstract: Small molecules aimed at type III secretion systems to inhibit bacterial virulence
From the themed collection: MedChemComm 2013 review articles
Review Article

Stabilised G protein-coupled receptors in structure-based drug design: a case study with adenosine A2A receptor

The first example of structure-based drug design with stabilised GPCRs has enabled the identification of a preclinical candidate for the treatment of Parkinson's disease.

Graphical abstract: Stabilised G protein-coupled receptors in structure-based drug design: a case study with adenosine A2A receptor
From the themed collection: MedChemComm 2013 review articles
Review Article

Approaches to discover non-ATP site kinase inhibitors

This review will highlight the most commonly used methods to discover small molecule Type III/IV kinase inhibitors.

Graphical abstract: Approaches to discover non-ATP site kinase inhibitors
From the themed collection: MedChemComm 2013 review articles
Review Article

Amino-derivatives of the sesquiterpene lactone class of natural products as prodrugs

The medicinal chemistry of amino-derivatives of the sesquiterpene lactones is described, beginning with synthetic development, moving into pharmacological applications, and finishing with clinical translation.

Graphical abstract: Amino-derivatives of the sesquiterpene lactone class of natural products as prodrugs
From the themed collection: MedChemComm 2013 review articles
Review Article

The status of type I polyketide synthase ketoreductases

The functional dissection of type I polyketide synthases has established that ketoreductases most commonly set the orientations of the hydroxyl and alkyl substituents of complex polyketides. Here we review the biochemical, structural biology, and engineering studies that have helped elucidate how stereocontrol is enforced by these enzymes.

Graphical abstract: The status of type I polyketide synthase ketoreductases
From the themed collection: MedChemComm 2013 review articles
Concise Article

Exploring the structural determinants of selective phosphopeptide recognition using bivalent metal-coordination complexes

We demonstrate that Lewis acidic coordination complexes equipped with cationic binding groups might be best utilized as selective receptors for binding phosphopeptides with anionic side chain residues proximal to the phosphorylated residue.

Graphical abstract: Exploring the structural determinants of selective phosphopeptide recognition using bivalent metal-coordination complexes
Concise Article

Experimental validation of in silico target predictions on synergistic protein targets

Two relatively recent trends have become apparent in current early stage drug discovery settings: firstly, a revival of phenotypic screening strategies and secondly, the increasing acceptance that some drugs work by modulating multiple targets in parallel (‘multi-target drugs’).

Graphical abstract: Experimental validation of in silico target predictions on synergistic protein targets
From the themed collection: New Talent
Concise Article

Mechanistic insight into inhibition of two-component system signaling

A scaffold that specifically interacts with the highly conserved ATP-binding domain in histidine kinases has been identified.

Graphical abstract: Mechanistic insight into inhibition of two-component system signaling
From the themed collection: New Talent
Concise Article

Interaction of long telomeric DNAs with macrocyclic hexaoxazole as a G-quadruplex ligand

The interactions of long telomeric DNAs, which mimic telomeres in living cells, with a macrocyclic hexaoxazole ligand L2H2-6OTD (2) were investigated by means of electrophoresis mobility shift assay, circular dichroism (CD) titration analysis, and DNA melting measurements.

Graphical abstract: Interaction of long telomeric DNAs with macrocyclic hexaoxazole as a G-quadruplex ligand
From the themed collection: New Talent
Concise Article

Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1 – the discovery of AZD2353

Focus on ligand efficiency, ligand lipophilicity efficiency, and conformational restriction led to the discovery of AZD2353.

Graphical abstract: Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1 – the discovery of AZD2353
From the themed collection: New Talent
Concise Article

Identification of false positives in “HTS hits to lead”: The application of Bayesian models in HTS triage to rapidly deliver a series of selective TRPV4 antagonists

The use of computational techniques to remove frequent hitters and enable the identification of a number of TRPV4 series from an HTS campaign will be described. The hit-to-lead efforts in one such series will also be discussed.

Graphical abstract: Identification of false positives in “HTS hits to lead”: The application of Bayesian models in HTS triage to rapidly deliver a series of selective TRPV4 antagonists
From the themed collection: New Talent
Concise Article

Structure–activity relationship studies using peptide arrays: the example of HIV-1 Rev–integrase interaction

We used peptide arrays to perform structure–activity relationship studies on anti-HIV peptides derived from HIV-1 integrase.

Graphical abstract: Structure–activity relationship studies using peptide arrays: the example of HIV-1 Rev–integrase interaction
From the themed collection: New Talent
Concise Article

Ring opening polymerization of mannosyl tricyclic orthoesters: rationalising the stereo and regioselectivity of glycosidic bond formation using quantum chemical calculations

Quantum chemical methods have been used to assess the physico-chemical origin of the stereo and regio-selectivity during glycosyl tricyclic orthoester polymerization. The subtle modulation of steric and electronic factors dramatically influences the reaction.

Graphical abstract: Ring opening polymerization of mannosyl tricyclic orthoesters: rationalising the stereo and regioselectivity of glycosidic bond formation using quantum chemical calculations
From the themed collection: New Talent
Concise Article

Discovery and optimization of efficacious neutral 4-amino-6-biphenyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one diacylglycerol acyl transferase-1 (DGAT1) inhibitors

Neutral DGAT1 inhibitors have been designed with comparable pre-clinical efficacy and PK/PD to those previously described for acidic inhibitors.

Graphical abstract: Discovery and optimization of efficacious neutral 4-amino-6-biphenyl-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5-one diacylglycerol acyl transferase-1 (DGAT1) inhibitors
From the themed collection: New Talent
Concise Article

The muraminomicin biosynthetic gene cluster and enzymatic formation of the 2-deoxyaminoribosyl appendage

The biosynthetic genes for muraminomicin F were uncovered, and the enzymatic synthesis of the unusual aminoribosyl appendage was delineated.

Graphical abstract: The muraminomicin biosynthetic gene cluster and enzymatic formation of the 2-deoxyaminoribosyl appendage
From the themed collection: New Talent
Concise Article

Optimization of triazole-based TGR5 agonists towards orally available agents

With the challenge of striking the balance of TGR5 potency and clearance, the screening strategy as well as medicinal chemistry strategy are discussed in this article.

Graphical abstract: Optimization of triazole-based TGR5 agonists towards orally available agents
From the themed collection: New Talent
Concise Article

Gobichelin A and B: mixed-ligand siderophores discovered using proteomics

PrISM (Proteomic Investigation of Secondary Metabolism), integrated with genomics and metabolomics, has led to the discovery of the new natural products, gobichelin A and B.

Graphical abstract: Gobichelin A and B: mixed-ligand siderophores discovered using proteomics
From the themed collection: New Talent
Concise Article

A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared

Many interaction types bind iNOS and inhibitors of its dimerization: docking methods reproduce geometries and quantum mechanics lipophilicity ligand efficiencies.

Graphical abstract: A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared
From the themed collection: New Talent
Concise Article

Navigations of chemical space to further the understanding of polypharmacology in human nuclear receptors

The article analyses properties featuring the binding site of human nuclear receptors and cognate ligands, investigating aspects of polypharmacology.

Graphical abstract: Navigations of chemical space to further the understanding of polypharmacology in human nuclear receptors
From the themed collection: New Talent
Concise Article

Discovery of a highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling

We discovered a novel heterobiaryl pyrazolopyridine skeleton as a selective FLT3 inhibitor from phenotype-based viability profiling and hypothesis-driven deconvolution.

Graphical abstract: Discovery of a highly selective FLT3 kinase inhibitor from phenotypic cell viability profiling
From the themed collection: New Talent
Concise Article

Two-in-one: a pH-sensitive, acridine-based, fluorescent probe binds G-quadruplexes in oncogene promoters

We report the synthesis of an acridine-containing cyanine dye and demonstrate its potential as a pH-responsive colorimetric indicator and fluorescent probe.

Graphical abstract: Two-in-one: a pH-sensitive, acridine-based, fluorescent probe binds G-quadruplexes in oncogene promoters
From the themed collection: New Talent
Concise Article

Mapping histamine H4 receptor–ligand binding modes

Computational prediction of ligand binding modes in G protein-coupled receptors (GPCRs) remains a challenging task. Systematic consideration of different protein modelling templates, ligand binding poses, and ligand protonation states in extensive molecular dynamics (MD) simulation studies enabled the prediction of ligand-specific mutation effects in the histamine H4 receptor, a key player in inflammation.

Graphical abstract: Mapping histamine H4 receptor–ligand binding modes
From the themed collection: New Talent
Concise Article

Sulforaphane and erucin, natural isothiocyanates from broccoli, inhibit bacterial quorum sensing

Sulforaphane and erucin, two natural isothiocyanates that are highly abundant in broccoli and other cruciferous vegetables, were found to strongly inhibit quorum sensing and virulence in Pseudomonas aeruginosa.

Graphical abstract: Sulforaphane and erucin, natural isothiocyanates from broccoli, inhibit bacterial quorum sensing
From the themed collection: New Talent
Concise Article

Synthesis and evaluation of stable substrate analogs as potential modulators of cyclodiphosphate synthase IspF

Stable IspF substrate analogs display distinct and unexpected properties as modulators of IspF and IspF–MEP activities.

Graphical abstract: Synthesis and evaluation of stable substrate analogs as potential modulators of cyclodiphosphate synthase IspF
From the themed collection: New Talent
Concise Article

Design and synthesis of a novel series of cyclohexyloxy-pyridyl derivatives as inhibitors of diacylglycerol acyl transferase 1

Design and synthesis of a novel series of cyclohexyloxy-pyridyl inhibitors of diacylglycerol acyl transferase 1.

Graphical abstract: Design and synthesis of a novel series of cyclohexyloxy-pyridyl derivatives as inhibitors of diacylglycerol acyl transferase 1
From the themed collection: New Talent
Concise Article

Phage display libraries of differently sized bicyclic peptides

Loop length variability in bicyclic peptide libraries increased the diversity of the motifs found in affinity selections towards the tumor-associated protease uPA.

Graphical abstract: Phage display libraries of differently sized bicyclic peptides
Concise Article

Truncated militarinone fragments identified by total chemical synthesis induce neurite outgrowth

Short analogs of militarinone D were prepared that omit the configurationally unstable triene side chain bearing stereogenic centers and cut down the number of synthetic steps by 12. These short natural product fragments induce neuritogenesis at markedly lower concentrations.

Graphical abstract: Truncated militarinone fragments identified by total chemical synthesis induce neurite outgrowth
From the themed collection: New Talent
Concise Article

Structure–activity relationship studies of miniproteins targeting the androgen receptor–coactivator interaction

Miniproteins featuring a stable α-helical motif allow exploring point mutations in and around FXXLF motifs to improve androgen receptor affinity.

Graphical abstract: Structure–activity relationship studies of miniproteins targeting the androgen receptor–coactivator interaction
From the themed collection: New Talent
Concise Article

The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains

Simple 1-substituted 5- and 6-isoxazolyl-benzimidazoles have been shown to be potent inhibitors of the BET bromodomains with selectivity over the related bromodomain of CBP.

Graphical abstract: The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains
From the themed collection: New Talent
Concise Article

Discovery of hydroxamate bioisosteres as KAT II inhibitors with improved oral bioavailability and pharmacokinetics

A series of kynurenine aminotransferase II (KAT II) inhibitors has been developed replacing the hydroxamate motif with a bioisostere.

Graphical abstract: Discovery of hydroxamate bioisosteres as KAT II inhibitors with improved oral bioavailability and pharmacokinetics
From the themed collection: New Talent
Concise Article

Design of membrane targeting tobramycin-based cationic amphiphiles with reduced hemolytic activity

Hemolysis caused by amphiphilic tobramycin antimicrobial agents is significantly reduced by altering the bond linking their hydrophobic and hydrophilic parts.

Graphical abstract: Design of membrane targeting tobramycin-based cationic amphiphiles with reduced hemolytic activity
From the themed collection: New Talent
Concise Article

Inhibitors of bacterial tubulin target bacterial membranes in vivo

The loss of ΔΨ disrupts the normal localization pattern of membrane-associated proteins. The cartoon and images depict the diffuse pattern of a polarly localized protein, MinD after reduction of ΔΨ in E. coli. The length of the line across the cell membrane depicts the relative magnitude of ΔΨ.

Graphical abstract: Inhibitors of bacterial tubulin target bacterial membranes in vivo
From the themed collection: New Talent
Concise Article

On the importance of synthetic organic chemistry in drug discovery: reflections on the discovery of antidiabetic agent ertugliflozin

The discovery of antidiabetic agent ertugliflozin is described. In this article, emphasis is placed on the critical role that organic synthesis played in influencing our medicinal chemistry strategy.

Graphical abstract: On the importance of synthetic organic chemistry in drug discovery: reflections on the discovery of antidiabetic agent ertugliflozin
From the themed collection: New Talent
Concise Article

Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonists

Solubility improvements in a series of GPR119 agonists are achieved through reduction of lipophilicity together with hydrogen bond acceptor modulation.

Graphical abstract: Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonists
From the themed collection: New Talent
Concise Article

A mast cell degranulation screening assay for the identification of novel mast cell activating agents

A cell-based screen to identify novel mast cell activating compounds.

Graphical abstract: A mast cell degranulation screening assay for the identification of novel mast cell activating agents
From the themed collection: New Talent
37 items

About this collection

New talents in Medicinal Chemistry. This issue will highlight medicinal chemistry research in its broadest sense, and showcase the strength of research being carried out by tomorrow's leaders in the field.

Articles in this themed issue will be added below as soon as possible after they are published. Please return to this page frequently to see the collection grow.

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