7ZUN
Crystal structure of PIM1 in complex with a Pyrrolo-Pyrazinone compound
Summary for 7ZUN
| Entry DOI | 10.2210/pdb7zun/pdb |
| Descriptor | Isoform 2 of Serine/threonine-protein kinase pim-1, (4~{S})-4-(2-azanylethyl)-6-phenyl-7-[3-(trifluoromethyloxy)phenyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1-ol (3 entities in total) |
| Functional Keywords | pim1, atp binding, kinase inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 36251.10 |
| Authors | Casale, E. (deposition date: 2022-05-12, release date: 2022-10-05, Last modification date: 2024-11-06) |
| Primary citation | Casuscelli, F.,Ardini, E.,Avanzi, N.,Badari, A.,Casale, E.,Disingrini, T.,Donati, D.,Ermoli, A.,Felder, E.R.,Galvani, A.,Isacchi, A.,Menichincheri, M.,Montemartini, M.,Orrenius, C.,Piutti, C.,Salom, B.,Papeo, G. Stereoselective synthesis of 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as PIM kinase inhibitors inspired from marine alkaloids. Chirality, 34:1437-1452, 2022 Cited by PubMed Abstract: We previously demonstrated that natural product-inspired 3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-ones derivatives delivered potent and selective PIM kinases inhibitors however with non-optimal ADME/PK properties and modest oral bioavailability. Herein, we describe a structure-based scaffold decoration and a stereoselective approach to this chemical class. The synthesis, structure-activity relationship studies, chiral analysis, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Compound 20c demonstrated excellent potency on PIM1 and PIM2 with exquisite kinases selectivity and PK properties that efficiently and dose-dependently promoted c-Myc degradation and appear to be promising lead compounds for further development. PubMed: 35959859DOI: 10.1002/chir.23501 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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