Contributors to our Emerging Investigators collection
RSC Medicinal Chemistry profiles the contributors to the ‘Emerging Investigators’ themed collection.
Review Article
Human chitinases and chitinase-like proteins as emerging drug targets – a medicinal chemistry perspective
Human chitinases and chitinase-like proteins are attractive drug targets. This review focuses on medicinal chemistry efforts directed at acidic mammalian chitinase (AMCase), chitotriosidase (CHIT1), and chitinase-3-like protein 1 (CHI3L1/YKL-40).
Synthetic strategies and medicinal chemistry perspectives of dual acting carbonic anhydrase modulators with monoamine oxidase and cholinesterase inhibitors
Dual acting carbonic anhydrase modulators with monoamine oxidase and cholinesterase inhibitors.
Review Article
Lazertinib: breaking the mold of third-generation EGFR inhibitors
Small molecules targeting activating mutations within the epidermal growth factor receptor (EGFR) are efficacious anticancer agents, particularly in non-small cell lung cancer (NSCLC).
Small molecule targeted protein degradation via the UPS: venturing beyond E3 substrate receptors
As the field of targeted protein degradation has advanced, it has expanded beyond traditional recruitment to E3 substrate receptors to new approaches involving recruitment to a variety of other components within the ubiquitin proteasome system.
Advances in antibacterial agents for Mycobacterium fortuitum
This review presents the recent findings on antibacterial agents against Mycobacterium fortuitum and reveals the most promising and effective chemical frameworks to inspire the development of new drugs.
Therapeutic upregulation of DNA repair pathways: strategies and small molecule activators
Potential therapeutic target proteins for upregulating DNA repair system are reviewed, along with reported small-molecule activators.
Probing non-peptide agonists binding at the human nociceptin/orphanin FQ receptor: a molecular modelling study
Short MD simulations help identify the putative bioactive conformation of small molecule agonists at the NOP receptor providing useful information for the structure-based design of novel analgesic drugs.
Structure-guided design of a truncated heterobivalent chemical probe degrader of IRE1α
The first degrader of an ER-resident protein (IRE1α) is described with properties more akin to a molecular glue than a traditional PROTAC, thus challenging the dogma of categorizing degrader modalities based on their physicochemical features.
Discovery and biological evaluation of nitrofuranyl–pyrazolopyrimidine hybrid conjugates as potent antimicrobial agents targeting Staphylococcus aureus and methicillin-resistant S. aureus
Nitrofuranyl–pyrazolopyrimidine conjugates exhibiting potent in vitro and in vivo efficacy against Gram-positive bacterial strain S. aureus and its resistant variant methicillin-resistant S. aureus.
Expanding the reaction toolbox for nanoscale direct-to-biology PROTAC synthesis and biological evaluation
High-throughput chemistry (HTC) and direct-to-biology (D2B) platforms allow for plate-based compound synthesis and biological evaluation of crude mixtures in cellular assays.
Enhanced skin penetration of curcumin by a nanoemulsion-embedded oligopeptide hydrogel for psoriasis topical therapy
Cur-CNEs/Gel combines the superior skin penetration efficiency of cell-penetrating peptide modified curcumin-loaded nanoemulsions and the prolonged skin retention ability of the oligopeptide hydrogel.
Research Article
Exploiting the DCAF16–SPIN4 interaction to identify DCAF16 ligands for PROTAC development
An HTRF assay was developed to measure the DCAF16–SPIN4 interaction and was subsequently employed to screen for DCAF16 recruiters. A hit compound, 2G07, was identified and further optimized into a PROTAC for the targeted degradation of FKBP12.
Research Article
A novel approach for the synthesis of the cyclic lipopeptide globomycin
Lipid swapping: a new approach for the synthesis of globomycin that allows for facile lipid diversification.
Research Article
Rationally modified SNX-class Hsp90 inhibitors disrupt extracellular fibronectin assembly without intracellular Hsp90 activity
Rationally modified Hsp90 inhibitors which retained of on-target activity but showed no engagement of intracellular Hsp90, or stimulation of the heat shock response, were found to significantly alter the extracellular fibronectin network.
Novel sulfonamides unveiled as potent anti-lung cancer agents via tumor pyruvate kinase M2 activation
Novel sulfonamides were developed rationally that emerged as potent anti-lung cancer (LC) agents.
Discovery and structure–activity relationship study of novel isoxazole-based small molecules targeting Zika virus infections
This study explores novel isoxazole-based small molecules, identifying compound 7l with potent antiviral activity against Zika virus (ZIKV) and an improved safety profile in vitro, highlighting its potential as a promising candidate for therapeutic development.
On-resin synthesis of Lanreotide epimers and studies of their structure–activity relationships
This report demonstrates the rapid and clean on-resin assembly of disulfide, which enabled impurity and biological profiling of eight possible epimers of a somatostatin analog, lanreotide.