Stereospecific access to α-haloalkyl esters enol ester epoxides and synthesis of a C3-C21 fragment of bastimolide A.

We report a 14-step synthesis of a C3-C21 fragment of bastimolides A and B, antimalarial macrocyclic polyketides. A crucial ring-opening reaction of an enol ester epoxide showed previously unexplored reactivity, leading to an asymmetric synthesis of α-haloalkyl esters. The α-haloalkyl ester synthesis was shown to be stereospecific, and provided access to a key α-silyloxyaldehyde to initiate application of configuration-encoded 1,5-polyol synthesis.

Identification of a Cannabinoid Receptor 2 Allosteric Site Using Computational Modeling and Pharmacological Analysis.

Emerging evidence has demonstrated that cannabinoid receptor 2 (CB) is involved in a number of diseases, such as neurodegenerative disorders and various types of cancer, making it an attractive pharmacological target. Classically, a protein active site or an orthosteric binding site, where the endogenous ligand binds to, is used as a target for the design of most small-molecule drugs. This can present challenges when it comes to phylogenetically related proteins that have similar orthosteric binding sites, such as the cannabinoid receptors.

RADEX: a rule-based clinical and radiology data extraction tool demonstrated on thyroid ultrasound reports.

Objectives: Radiology reports contain valuable information for research and audits, but relevant details are often buried within free-text fields. This makes them challenging and time-consuming to extract for secondary analyses, including training artificial intelligence (AI) models.

Materials And Methods: This study presents a rule-based RAdiology Data EXtraction tool (RADEX) to enable biomedical researchers and healthcare professionals to automate information extraction from clinical documents.

A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma.

Background: This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma.

Methods: Patients aged 2-21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28-day cycles.

Production of recombinant coiled coil silk proteins for materials synthesis.

Rational design of fundamentally new advanced materials would be facilitated by availability of polymers with controlled monomer sequence. Recombinant proteins offer polymers with controlled monomer sequence but are underrepresented in material science, in part because suitable proteins cannot be produced at commercial levels in recombinant systems. The silk proteins of honeybees fulfil the requirements for rational materials design and can be produced at commercially viable levels.