Lourdes Rueda

TL;DR: The discovery of GSK3685032 is reported, a potent first-in-class DNMT1-selective inhibitor that was shown via crystallographic studies to compete with the active-site loop ofDNMT1 for penetration into hemi-methylated DNA between two CpG base pairs.

TL;DR: It is concluded that in these preclinical models, selective, reversible inhibition of DNMT1 is sufficient for the induction of HbF, and is well-tolerated.

TL;DR: Rapid triaging of three series of related hits selected from the Tres Cantos Anti-Malarial Set (TCAMS) are described, and a triazolopyrimidine series was deprioritized due to delayed inhibition of parasite growth.

TL;DR: The biological characterization of this chemical family with the generic name cyclopropyl carboxamides is described, showing that inhibition of their still unknown target has very favorable pharmacological consequences but the compounds themselves seem to select for resistance at a high frequency.

TL;DR: The medicinal chemistry efforts focused on a cGMP-dependent protein kinase (PKG) inhibitor scaffold are described, leading to the identification of novel chemical entities with very potent, similar to artemisinins, fast-killing potency against asexual blood stages that cause disease, and activity against gametocyte activation that is required for transmission.