Structure- and Property-Based Optimization of Efficient Pan-Bromodomain and Extra Terminal Inhibitors to Identify Oral and Intravenous Candidate I-BET787.

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins are important epigenetic regulators that elicit their effect through binding histone tail N-acetyl lysine (KAc) post-translational modifications. Recognition of such markers has been implicated in a range of oncology and immune diseases and, as such, small-molecule inhibition of the BET family bromodomain-KAc protein-protein interaction has received significant interest as a therapeutic strategy, with several potential medicines under clinical evaluation. This work describes the structure- and property-based optimization of a ligand and lipophilic efficient pan-BET bromodomain inhibitor series to deliver candidate I-BET787 (70) that demonstrates efficacy in a mouse model of inflammation and suitable properties for both oral and intravenous (IV) administration. This focused two-phase explore-exploit medicinal chemistry effort delivered the candidate molecule in 3 months with less than 100 final compounds synthesized.

First record of Leptoglossusoccidentalis Heidemann, 1910 (Hemiptera, Coreidae) in the Canary Islands, a novel pine pest detected through citizen science in an oceanic archipelago.

Background: The 'western seed bug', known as Leptoglossusoccidentalis, is considered a global invasive species that has experienced a recent rapid expansion worldwide, becoming an important pest species for coniferous forests. New information: With the 'Canary Islands early-warning network for the detection and intervention of invasive exotic species' (RedEXOS), this species was detected for the first time in the Canarian archipelago in an urban area in the eastern part of the island of Gran Canaria. This early detection is crucial for understanding the potential damage in one of the islands with the highest surface area of natural endemic pine forest.

Rediscovery of the Canary Islands endemic Aphaenogaster hesperia Santschi, 1911 (Hymenoptera, Formicidae, Myrmicinae).

The Canary Islands endemic species Aphaenogaster hesperia Santschi, 1911 was described based solely on two workers captured in a north-western coastal area of Tenerife (Canary Islands) in 1902 and 1903. The species has not been recorded in the last 100 years and only information on its type locality is known. This species, belonging to the crocea group, has been recently rediscovered in a new site within a pine forest at 950 m a.s.l. The new area is a very different habitat, revealing a lack of ecological knowledge of the species, which may have caused the species to have remained unnoticed for more than 100 years. Novel distributional and morphological data are provided.