3DT1
P38 Complexed with a quinazoline inhibitor
Summary for 3DT1
| Entry DOI | 10.2210/pdb3dt1/pdb |
| Related | 3ds6 |
| Descriptor | Mitogen-activated protein kinase 14, N-cyclopropyl-4-methyl-3-{2-[(2-morpholin-4-ylethyl)amino]quinazolin-6-yl}benzamide (3 entities in total) |
| Functional Keywords | kinase inhibitor complex, alternative splicing, atp-binding, cytoplasm, kinase, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm (By similarity): Q16539 |
| Total number of polymer chains | 1 |
| Total formula weight | 44319.54 |
| Authors | Herberich, B.,Syed, R.,Li, V.,Tasker, A.S. (deposition date: 2008-07-14, release date: 2008-10-14, Last modification date: 2024-02-21) |
| Primary citation | Herberich, B.,Cao, G.Q.,Chakrabarti, P.P.,Falsey, J.R.,Pettus, L.,Rzasa, R.M.,Reed, A.B.,Reichelt, A.,Sham, K.,Thaman, M.,Wurz, R.P.,Xu, S.,Zhang, D.,Hsieh, F.,Lee, M.R.,Syed, R.,Li, V.,Grosfeld, D.,Plant, M.H.,Henkle, B.,Sherman, L.,Middleton, S.,Wong, L.M.,Tasker, A.S. Discovery of highly selective and potent p38 inhibitors based on a phthalazine scaffold. J.Med.Chem., 51:6271-6279, 2008 Cited by PubMed Abstract: Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic properties, of which compound 16 displayed the most desirable profile. Oral dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease in TNFalpha production. PubMed: 18817365DOI: 10.1021/jm8005417 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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