9SUV
Structure of an inhibitor of Human TGF-beta Type I Receptor
This is a non-PDB format compatible entry.
Summary for 9SUV
| Entry DOI | 10.2210/pdb9suv/pdb |
| Descriptor | TGF-beta receptor type-1, ~{N}-[4-[[6-(5-chloranyl-2-fluoranyl-phenyl)-3-(2-hydroxyethylsulfanyl)pyridazin-4-yl]amino]pyridin-2-yl]-3-(4-methylpiperazin-1-yl)propanamide, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | human tgf-beta type i receptor, tgfbetar1, cytokine, inhibitor, kinase, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35577.35 |
| Authors | Caria, S.,Hole, A.J. (deposition date: 2025-09-30, release date: 2026-05-27, Last modification date: 2026-06-24) |
| Primary citation | Ronchi, P.,Pizzirani, D.,Pala, D.,Capelli, A.M.,Rescigno, D.,Bertani, B.,Trist, I.M.L.,Milioli, M.,Cesari, N.,Federico, G.,Pappani, A.,Venturi, L.,Pecorari, D.,Guariento, S.,Marchini, G.,Stellari, F.F.,Xanxo Fernandez, S.,Biagetti, M.,Civelli, M.,Bianchi, F.,Remelli, R.,Barilli, A.,Pompilio, D.,Hole, A.J.,Caria, S.,Armani, E. Discovery of a Novel Lung-Restricted ALK5 Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis. J.Med.Chem., 69:13002-13027, 2026 Cited by PubMed Abstract: As part of a therapeutic approach to idiopathic pulmonary fibrosis (IPF) using inhaled ALK5 inhibitors, which enable targeted lung delivery while minimizing systemic side effects, this work describes the optimization process of a previously reported series featuring a 4,6-disubstituted pyridazine core. The medicinal chemistry exploration, aimed at increasing cellular potency while keeping physicochemical and ADME properties favorable for inhalation, was directed to the functionalization of the 3-position in the pyridazine core. An efficient SAR exploration, supported by a late-stage functionalization (LSF) approach, led to the identification of a small set of compounds worthy of characterization. Compound showed a persistent and lung-restricted target engagement in a pharmacodynamic model, which well-correlated with its solubility measured in simulated lung fluid (SLF). When tested in a mouse model of lung fibrosis, showed remarkable efficacy, thus representing an advanced lead candidate for the development of topical antifibrotic therapeutics. PubMed: 42152170DOI: 10.1021/acs.jmedchem.5c03825 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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