TAK-593 / Takeda - LARVOL DELTA

Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. (PubMed, Purinergic Signal) - "The hit compound ABBV-744, an experimental anticancer drug with a 6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine scaffold, had multifaceted interactions with the P2YR family: hP2Y6R inhibition in a non-surmountable fashion, suggesting that noncompetitive antagonism, and hP2Y1R enhancement, but not hP2Y14R binding inhibition. Other machine learning-selected compounds were either weak (experimental anti-asthmatic drug AZD5423 with a phenyl-1H-indazole scaffold) or inactive in inhibiting the hP2Y6R. Experimental drugs TAK-593 and GSK1070916 (100 µM) inhibited P2Y14R fluorescent binding by 50% and 38%, respectively, and all other compounds by < 20%. Thus, machine learning has led the way toward revealing previously unknown modulators of several P2YR subtypes that have varied effects."

Journal • Machine learning • Asthma • Astrocytoma • Brain Cancer • CNS Disorders • Immunology • Metabolic Disorders • Oncology • Respiratory Diseases • Solid Tumor

Potential of TAK-593 ophthalmic emulsion for the treatment of age-related macular degeneration. (PubMed, Biol Pharm Bull) - "The delivery of TAK-593 to the posterior eye was increased by the formulation concentration and the addition of viscosity enhancers.In the laser-induced choroidal neovascularization model, TAK-593 emulsion eye drops showed the same angiogenesis-suppression efficacy as anti-VEGF antibody intravitreal injection. From these results, it was revealed that TAK-593 with an effective drug concentration can be delivered to the posterior eye by non-invasive eye drop administration."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders

C3 regioselectivity: a major constraint in the drug development with imidazo[1,2-a]pyridines. (PubMed, Future Med Chem) - No abstract available

Journal • Oncology

[VIRTUAL] Aryl Hydrocarbon Receptor Plays an Essential Role in the Pathogenesis of Pulmonary Arterial Hypertension (AHA 2021) - "RNA-seq and qRT-PCR were performed on specimens from SU5416/Hypoxia (SuHx) rats, including lungs and the peripheral blood mononuclear cells (PBMCs), and PBMCs of PAH patients. AHR agonistic activity in serum was judged by luciferase reporter assay. WT rats treated with the potent endogenous AHR agonist (6-formylindolo[3,2-b]carbazole) in combination with hypoxia, developed severe pulmonary hypertension (PH) with plexiform-like lesions, whereas WT rats treated with the potent VEGFR2 inhibitors (KI8751 and TAK-593) did not... AHR plays crucial roles in the development and progression of PAH, indicating that this receptor is a potential target for both diagnosis and treatment of PAH."

Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CD4 • IL21 • MRC1