8S3R
HUMAN PI3KDELTA IN COMPLEX WITH PYRIDAZINONE INHIBITOR 7
This is a non-PDB format compatible entry.
Summary for 8S3R
| Entry DOI | 10.2210/pdb8s3r/pdb |
| Descriptor | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, Phosphatidylinositol 3-kinase regulatory subunit alpha, 5-[(1~{S})-1-[4-azanyl-3-(5-oxidanylpyridin-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-4-cyclopentyl-2-(phenylmethyl)pyridazin-3-one, ... (4 entities in total) |
| Functional Keywords | pi3kdelta kinase, pi3kdelta kinase inhibitor, transferase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 137988.76 |
| Authors | Pala, D.,Bruno, P.,Capelli, A.M.,Biagetti, M. (deposition date: 2024-02-20, release date: 2024-07-03, Last modification date: 2024-07-24) |
| Primary citation | Bruno, P.,Micoli, A.,Corsi, M.,Pala, D.,Guariento, S.,Fiorelli, C.,Ronchi, P.,Fioni, A.,Gallo, P.M.,Marenghi, G.,Bertolini, S.,Capacchi, S.,Mileo, V.,Biagetti, M.,Capelli, A.M. Discovery and Optimization of Pyridazinones as PI3K delta Selective Inhibitors for Administration by Inhalation. J.Med.Chem., 67:11103-11124, 2024 Cited by PubMed Abstract: A hit-to-lead campaign pursuing the identification of novel inhalant small-molecule phosphatidylinositol 3-kinase (PI3K) inhibitors for the treatment of inflammatory respiratory diseases is disclosed. A synthetically versatile pyridazin-3(2)-one scaffold was designed, and three exit vectors on the core moiety were used to explore chemical diversity and optimize pharmacological and absorption, distribution, metabolism, and excretion (ADME) properties. Desired modulation of PI3Kδ selectivity and cellular potency as well as ADME properties in view of administration by inhalation was achieved. Intratracheal administration of lead compound resulted in a promising pharmacokinetic profile, thus demonstrating that the optimization strategy of profiles successfully translated to an setting. PubMed: 38907711DOI: 10.1021/acs.jmedchem.4c00610 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.28 Å) |
Structure validation
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