High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor.

GDC-6036 is a covalent KRAS G12C inhibitor that demonstrates high potency and selectivity. Structurally, GDC-6036 consists of several motifs that make the analytical characterization of this molecule challenging, including a highly basic pyrrolidine motif bonded to a quinazoline ring via an ether bond and an atropisomeric carbon-carbon bond between functionalized pyridine and quinazoline groups. Structurally, the desired atropisomer was synthesized via an atroposelective Negishi coupling with very high yield.

Safety profile of proprotein convertase subtilisin/kexin type 9 inhibitors alirocumab and evolocumab: an updated meta-analysis and meta-regression.

Background: The use of alirocumab and evolocumab is generally safe and well-tolerated. However, concerns remain about their long-term safety, especially with regard to new-onset or worsening diabetes mellitus (DM). We aim to assess the safety profile of alirocumab and evolocumab compared to comparator.

Atherosclerotic coronary plaque regression from lipid-lowering therapies: A meta-analysis and meta-regression.

Background: Studies reporting collective and comprehensive data on plaque regression of different lipid-lowering therapies (LLTs) are limited.

Objectives: We evaluated plaque regression of LLTs based on multiple markers and performed subgroup analyses based on LLT type and post-treatment LDL-C levels.

Methods: A literature search was performed to identify studies assessing plaque regression from LLTs.

Sex-related differences in benefits of anticoagulation therapy in elderly patients with atrial fibrillation: a subanalysis of the EMERG-AF study.

Objectives: To analyze the long-term benefits and safety of oral anticoagulation therapy prescribed in emergency departments for elderly patients with atrial fibrillation, and to detect any sex-related differences present.

Material And Methods: Post-hoc analysis of data compiled by the EMERG-AF group (Spanish acronym for Emergency Department Stroke Prophylaxis and Guidelines Implementation in Atrial Fibrillation). Consecutive patients aged 75 years or older with atrial fibrillation who were treated in 62 EDs were included.

Long-term prognosis and emergency management for patients with an implantable cardioverter defibrillator: the EMERGE-ICD study.

Objectives: Patients with implantable cardioverter defibrillators (ICDs) are at risk of serious complications that are often treated in hospital emergency departments (EDs). The EMERG-ICD study (Emergency Department Management and Long-term Prognosis for Patients with ICDs) analysed management and long-term prognosis of ED patients with an ICD after an acute clinical event.

Material And Methods: Observational multicenter cohort study including consecutive adult patients with ICDs who came to 27 hospital EDs in Spain for treatment and were followed for 10 years.