4AS0
Cyclometalated Phthalimides as Protein Kinase Inhibitors
Summary for 4AS0
| Entry DOI | 10.2210/pdb4as0/pdb |
| Related | 1XQZ 1XR1 1XWS 1YHS 1YI3 1YI4 1YWV 1YXS 1YXT 1YXU 1YXV 1YXX 2BIK 2BIL 2BZH 2BZI 2BZJ 2BZK 2C3I 2J2I 2XIX 2XIY 2XIZ 2XJ0 2XJ1 2XJ2 4A7C 4ALU 4ALV 4ALW |
| Descriptor | SERINE/THREONINE-PROTEIN KINASE PIM-1, PHTALIMIDE-RUTHENIUM COMPLEX (3 entities in total) |
| Functional Keywords | transferase, pim1, octasporine, ruthenium, kinase inhibitor |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309 |
| Total number of polymer chains | 1 |
| Total formula weight | 31950.29 |
| Authors | Blanck, S.,Geisselbrecht, Y.,Middel, S.,Mietke, T.,Harms, K.,Essen, L.-O.,Meggers, E. (deposition date: 2012-04-27, release date: 2012-10-03, Last modification date: 2023-12-20) |
| Primary citation | Blanck, S.,Geisselbrecht, Y.,Kraling, K.,Middel, S.,Mietke, T.,Harms, K.,Essen, L.-O.,Meggers, E. Bioactive Cyclometalated Phthalimides: Design, Synthesis and Kinase Inhibition. Dalton Trans, 41:9337-, 2012 Cited by PubMed Abstract: The regioselective cyclometalation of 4-(pyridin-2-yl)phthalimide was exploited for the economical design of organometallic protein kinase inhibitors. 4-(Pyridin-2-yl)phthalimide can be prepared from inexpensive 4-bromophthalimide in just three steps including one Pd-catalyzed Stille cross-coupling. The versatility of this new ligand was demonstrated with the synthesis of ruthenium(II) half-sandwich as well as octahedral ruthenium(II) and iridium(III) complexes. The regioselectivity of the C-H activation in the course of the cyclometalation can be influenced by the reaction conditions and the steric demand of the introduced metal complex fragment. The biological activity of this new class of metalated phthalimides was evaluated by profiling two representative members against a large panel of human protein kinases. A cocrystal structure of one metallo-phthalimide with the protein kinase Pim1 confirmed an ATP-competitive binding with the intended hydrogen bonding between the phthalimide moiety and the hinge region of the ATP-binding site. PubMed: 22733119DOI: 10.1039/C2DT30940H PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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