Themed collection Molecular Pharmacology

An increasing focus on complex biology to cure diseases rather than merely treat symptoms is transforming how drug discovery can be approached, and expands the arsenal of drug modalities and modes-of-actions that can be leveraged to modify diseases.

RNA is one of the most intriguing and promising biological targets for the discovery of innovative drugs in many pathologies and various biologically relevant RNAs that could serve as drug targets have already been identified.

Structure–activity relationship and crystallographic studies on HIF prolyl hydroxylase inhibitors reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.

Metabotropic glutamate type 7 (mGlu₇) receptor is a member of the group III family of mGlu receptors.

Simulations show under which conditions increasing a drug’s k_on can bring about faster clinical action.

B,B-Fluoro-perfluoroalkyl BODIPYs 2 (R = CF₃) and 3 (R = C₂F₅) exhibited higher photo- and chemical stability than B,B-difluoro-BODIPY 1.

A modular chemistry toolbox was developed for cereblon-directed PROTACs.

Fluorescent probes derived from the fluoroquinolone antibiotic ciprofloxacin were synthesised using a Cu(I)-catalysed azide–alkyne cycloaddition (CuAAC) to link a ciprofloxacin azide derivative with alkyne-substituted green and blue fluorophores.

Compounds 1 and 2 disrupt M. tuberculosis membrane potential and demonstrate bactericidal activity against non-replicating M. tuberculosis in pH 4.5 buffer.

Anionic moieties can be used to control the cell-permeability of drugs and used to select the appropriate target identification method for phenotypic screening hits.

Thienopyridone and iminothienopyridinedione inhibit protein phosphatases through a redox mechanism to oxidise the active site cysteine.

Insights into the role of 4′-PP- and long acyl chains-dependent interactions in human ACPM function.

A fragment library of electrophilic small heterocycles was characterized through cysteine-reactivity and aqueous stability tests that suggested their potential as covalent warheads.

A novel strategy for the synthesis of vinyl sulfonamide fragments for application to irreversible protein tethering.

Herein we continued our previous work on the development of CB2 ligands, reporting the design and synthesis of a series of benzimidazole-containing derivatives that were explored as selective CB2 ligands.

Identification of HRAS i-motif-binding small molecules.

Adenines that incorporate known agonist affinity-enhancing substituents are A₃AR-selective antagonists.

Increased expression of the Tribbles pseudokinase 1 gene (TRIB1) is associated with lower plasma levels of LDL cholesterol and triglycerides, higher levels of HDL cholesterol and decreased risk of coronary artery disease.

A ⁶⁸Ga-labelled ghrelin(1-19) analogue is described as a high affinity peptide for ghrelin receptor PET imaging using a sequence derived directly from the endogenous ligand, yet modified for improved stability.

A probe that conjugated a TrkC targeting agent with a zwitterionic near-infrared dye was reported for imaging of metastatic breast cancer.