5NGB
X-Ray Diffraction Crystal Structure of the murine PI3K p110delta in complex with a pan inhibitor
Summary for 5NGB
| Entry DOI | 10.2210/pdb5ngb/pdb |
| Descriptor | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, 3-[[4-(2-morpholin-4-yl-4-oxidanylidene-3~{H}-quinolin-8-yl)-1,2,3-triazol-1-yl]methyl]benzoic acid (2 entities in total) |
| Functional Keywords | pi3k p110, transferase |
| Biological source | Mus musculus (House Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 124744.51 |
| Authors | Berndt, A.,Williams, R.L. (deposition date: 2017-03-17, release date: 2017-09-13, Last modification date: 2024-01-17) |
| Primary citation | Pirali, T.,Ciraolo, E.,Aprile, S.,Massarotti, A.,Berndt, A.,Griglio, A.,Serafini, M.,Mercalli, V.,Landoni, C.,Campa, C.C.,Margaria, J.P.,Silva, R.L.,Grosa, G.,Sorba, G.,Williams, R.,Hirsch, E.,Tron, G.C. Identification of a Potent Phosphoinositide 3-Kinase Pan Inhibitor Displaying a Strategic Carboxylic Acid Group and Development of Its Prodrugs. ChemMedChem, 12:1542-1554, 2017 Cited by PubMed Abstract: Activation of the phosphoinositide 3-kinase (PI3K) pathway is a key signaling event in cancer, inflammation, and other proliferative diseases. PI3K inhibitors are already approved for some specific clinical indications, but their systemic on-target toxicity limits their larger use. In particular, whereas toxicity is tolerable in acute treatment of life-threatening diseases, this is less acceptable in chronic conditions. In the past, the strategy to overcome this drawback was to block selected isoforms mainly expressed in leukocytes, but redundancy within the PI3K family members challenges the effectiveness of this approach. On the other hand, decreasing exposure to selected target cells represents a so-far unexplored alternative to circumvent systemic toxicity. In this manuscript, we describe the generation of a library of triazolylquinolones and the development of the first prodrug pan-PI3K inhibitor. PubMed: 28857471DOI: 10.1002/cmdc.201700340 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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