7SLX
Vanin-1 complexed with Compound 11
Summary for 7SLX
| Entry DOI | 10.2210/pdb7slx/pdb |
| Descriptor | Pantetheinase, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-6)-[beta-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | pantetheine, sbdd, pyrimdine carboxamide, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 56292.30 |
| Authors | Vajdos, F.F. (deposition date: 2021-10-25, release date: 2022-01-12, Last modification date: 2024-10-30) |
| Primary citation | Casimiro-Garcia, A.,Allais, C.,Brennan, A.,Choi, C.,Dower, G.,Farley, K.A.,Fleming, M.,Flick, A.,Frisbie, R.K.,Hall, J.,Hepworth, D.,Jones, H.,Knafels, J.D.,Kortum, S.,Lovering, F.E.,Mathias, J.P.,Mohan, S.,Morgan, P.M.,Parng, C.,Parris, K.,Pullen, N.,Schlerman, F.,Stansfield, J.,Strohbach, J.W.,Vajdos, F.F.,Vincent, F.,Wang, H.,Wang, X.,Webster, R.,Wright, S.W. Discovery of a Series of Pyrimidine Carboxamides as Inhibitors of Vanin-1. J.Med.Chem., 65:757-784, 2022 Cited by PubMed Abstract: A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1. Through optimization of potency and physicochemical and ADME properties, and guided by co-crystal structures with vanin-1, was identified with a suitable profile for advancement into preclinical development. PubMed: 34967602DOI: 10.1021/acs.jmedchem.1c01849 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.35 Å) |
Structure validation
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