5L3A
Fragment-based discovery of 6-arylindazole JAK inhibitors
Summary for 5L3A
| Entry DOI | 10.2210/pdb5l3a/pdb |
| Descriptor | Tyrosine-protein kinase JAK2, ~{N}-(1~{H}-indazol-4-yl)methanesulfonamide (3 entities in total) |
| Functional Keywords | double f mutant, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34741.77 |
| Authors | Soerensen, M.D.,Dack, K.N.,Greve, D.R.,Ritzen, A. (deposition date: 2016-04-06, release date: 2016-04-27, Last modification date: 2024-05-08) |
| Primary citation | Ritzen, A.,Srensen, M.D.,Dack, K.N.,Greve, D.R.,Jerre, A.,Carnerup, M.A.,Rytved, K.A.,Bagger-Bahnsen, J. Fragment-Based Discovery of 6-Arylindazole JAK Inhibitors. Acs Med.Chem.Lett., 7:641-646, 2016 Cited by PubMed Abstract: Janus kinase (JAK) inhibitors are emerging as novel and efficacious drugs for treating psoriasis and other inflammatory skin disorders, but their full potential is hampered by systemic side effects. To overcome this limitation, we set out to discover soft drug JAK inhibitors for topical use. A fragment screen yielded an indazole hit that was elaborated into a potent JAK inhibitor using structure-based design. Growing the fragment by installing a phenol moiety in the 6-position afforded a greatly improved potency. Fine-tuning the substituents on the phenol and sulfonamide moieties afforded a set of compounds with lead-like properties, but they were found to be phototoxic and unstable in the presence of light. PubMed: 27326341DOI: 10.1021/acsmedchemlett.6b00087 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
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