9 research outputs found
High-content screen identifies cyclosporin A as a novel ABCA3-specific molecular corrector.
ATP-binding cassette (ABC) subfamily A member 3 (ABCA3) is a lipid transporter expressed in alveolar type II cells and localized in the limiting membrane of lamellar bodies. It is crucial for pulmonary surfactant storage and homeostasis. Mutations in the ABCA3 gene are the most common genetic cause of respiratory distress syndrome in mature newborns and interstitial lung disease in children. Apart from lung transplantation, there is no cure available. To address the lack of causal therapeutic options for ABCA3 deficiency, a rapid and reliable approach is needed to investigate variant-specific molecular mechanisms and to identify pharmacological modulators for mono- or combination therapies. To this end, we developed a phenotypic cell-based assay to autonomously identify ABCA3 wild-type-like or mutant-like cells by using machine-learning algorithms aimed at identifying morphological differences in WT and mutant cells. The assay was subsequently used to identify new drug candidates for ABCA3 specific molecular correction by high-content screening of 1,280 food and drug administration-approved small molecules. Cyclosporin A (CsA) was identified as a potent corrector, specific for some, but not all ABCA3 variants. Results were validated by our previously established functional small format assays. Hence, CsA may be selected for orphan drug evaluation in controlled repurposing trials in patients
Combined Homogeneous and Heterogeneous Catalysts. Rhodium and Platinum Isocyanide Complexes Tethered on Silica-Supported Metal Heterogeneous Catalysts: Arene and Cyclohexanone Hydrogenation
Alkyl and Hydrido Complexes of Platinum(IV) Supported by the Bis(8-quinolyl)methylsilyl Ligand
Flexible, Bowl-Shaped N-Heterocyclic Carbene Ligands: Substrate Specificity in Iridium-Catalyzed Ketone Hydrosilylation
Iridium-Catalyzed Silylation
In this chapter, homogeneous iridium-catalyzed silylation reactions are reviewed, focusing primarily on their synthetic utility. Additionally, relevant catalytic cycles are commented, paying especial attention to those that are more representative of each type of process. The chapter is divided into two main types of reactions, namely, hydrosilylation and C–H bond silylation. The former deals with the hydrosilylation of polar unsaturated bonds (ketones and imines) and non-polar unsaturated bonds (alkenes and alkynes). The latter covers the directed and non-directed C–H bond silylation of alkenes, alkynes, arenes, and alkanes – mainly comprising dehydrogenative silylation reactions, which may occur in the presence or absence of a hydrogen acceptor.This work was supported by the “Ramón y Cajal” program (RYC2016-20864) (FSE/Agencia Estatal de Investigación) (M. I.) and the Spanish Ministry of Science, Innovation and Universities (RTI2018-099136-A-I00).Peer reviewe