Age-Related Ventricular Tachycardia Substrate Characteristics for Repaired Tetralogy of Fallot Before Transcatheter Pulmonary Valve Placement.

Background: Ventricular tachycardia (VT) substrate characteristics before transcatheter pulmonary valve replacement (TPVR) in repaired tetralogy of Fallot (rTOF) are unknown.

Objectives: In this study, the authors sought to evaluate substrates for sustained monomorphic VT before TPVR in rTOF.

Methods: Retrospective (2017 to 2021) and prospective (commencing 2021) rTOF patients with native right ventricular outflow tract referred for electrophysiology study (EPS) before TPVR were included.

Patient-Reported Outcomes Among Adults With Congenital Heart Disease in the Congenital Heart Initiative Registry.

Importance: In the US, there are more than 1.5 million adults living with congenital heart disease (CHD). The Congenital Heart Initiative (CHI) is a digital, online, patient-empowered registry that was created to advance multicenter research and improve clinical care by gathering patient-reported outcomes (PROs) in adults with CHD.

Discovery of the Clinical Candidate IDOR-1117-2520: A Potent and Selective Antagonist of CCR6 for Autoimmune Diseases.

Migration of immune cells to sites of inflammation is a critical step in the body's response to infections but also during autoimmune flares. Chemokine receptors, members of the GPCR receptors, are instrumental in directing specific cell types to their target organs. Herein, we describe a highly potent small molecule antagonist of the chemokine receptor CCR6, which came out of fine-tuned structural elaborations from a proprietary HTS hit.

Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.

The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens. Despite advances in treatment with immune checkpoint inhibitors, there is an unmet need in the treatment of MSI cancers. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy.