Publications by authors named "G A Lamont"
Porphyromonas gingivalis is a Gram-negative, anaerobic oral pathobiont, an etiological agent of periodontitis and the most commonly studied periodontal bacterium. Multiple low passage clinical isolates were sequenced, and their genomes compared to several laboratory strains. Phylogenetic distances were mapped, a gene absence-presence matrix generated, and core (present in all genomes) and accessory (absent in one or more genomes) genes delineated.
View Article and Find Full Text PDFPRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel "MTA-cooperative" compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties.
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- Androgen receptor (AR) signaling is crucial in the development of prostate cancer, prompting research into effective treatments.
- The study focused on creating and refining AR PROTAC degraders, which work by recruiting the Cereblon (CRBN) E3 ligase to induce AR degradation.
- The lead compound, AZ'3137, exhibited strong degradation of AR and its L702H mutant, good oral bioavailability, and effectively inhibited AR signaling and tumor growth in mouse models.
Article Synopsis
- Targeting the estrogen receptor alpha (ERα) pathway is a proven strategy for treating estrogen receptor-positive (ER+) breast cancers, leading to the development of a new type of drug called a PROTAC designed to degrade ERα.
- In laboratory tests, this PROTAC showed strong effectiveness in degrading ERα and blocking its activity in breast cancer cells, but results did not match when tested in live models.
- The discrepancy is attributed to the PROTAC’s linker being metabolically unstable, which leads to the creation of competing metabolites that interfere with the drug's ability to degrade ERα; this emphasizes the importance of designing more stable PROTACs for better treatment outcomes.
AstraZeneca chemists have been using the AI retrosynthesis tool AiZynth for three years. In this article, we present seven examples of how medicinal chemists using AiZynth positively impacted their drug discovery programmes. These programmes run the gamut from early-stage hit confirmation to late-stage route optimisation efforts.
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