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Pyridazines

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Bionalytical validation study for the determination of unbound ambrisentan in human plasma using rapid equilibrium dialysis followed by ultra performance liquid chromatography coupled to mass spectrometry.

Journal of pharmaceutical and biomedical analysis
Ambrisentan is a highly selective endothelin-1 type A receptor antagonist indicated for use in the treatment of pulmonary hypertension. In this study an assay was developed and validated for the quantification of total and unbound (free) concentratio...

Chromatographic Study of Azintamide in Bulk Powder and in Pharmaceutical Formulation in the Presence of Its Degradation Form.

Journal of AOAC International
Two specific, sensitive, and precise stability-indicating chromatographic methods were developed, optimized, and validated for the determination of Azintamide (AZ) in the presence of its degradation product. The first method was TLC combined with the...

A deep learning approach to identify gene targets of a therapeutic for human splicing disorders.

Nature communications
Pre-mRNA splicing is a key controller of human gene expression. Disturbances in splicing due to mutation lead to dysregulated protein expression and contribute to a substantial fraction of human disease. Several classes of splicing modulator compound...

Discovery of Pyrazolo[3,4-]pyridazinone Derivatives as Selective DDR1 Inhibitors via Deep Learning Based Design, Synthesis, and Biological Evaluation.

Journal of medicinal chemistry
Alterations of discoidin domain receptor1 (DDR1) may lead to increased production of inflammatory cytokines, making DDR1 an attractive target for inflammatory bowel disease (IBD) therapy. A scaffold-based molecular design workflow was established and...

Explainable machine learning prediction of edema adverse events in patients treated with tepotinib.

Clinical and translational science
Tepotinib is approved for the treatment of patients with non-small-cell lung cancer harboring MET exon 14 skipping alterations. While edema is the most prevalent adverse event (AE) and a known class effect of MET inhibitors including tepotinib, there...