5CTC

Humanized yeast ACC carboxyltransferase domain bound to tert-butyl 7-[(7-methyl-1H-indazol-5-yl)carbonyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate

Summary for 5CTC

• Entry DOI: 10.2210/pdb5ctc/pdb
• Related: 5CTB 5CTE
• Descriptor: Acetyl-CoA carboxylase, tert-butyl 7-[(7-methyl-1H-indazol-5-yl)carbonyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate, SULFATE ION, ... (4 entities in total)
• Functional Keywords: acc, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Cytoplasm: Q00955
• Total number of polymer chains: 3
• Total formula weight: 263104.14

Authors

Vajdos, F.F. (deposition date: 2015-07-23, release date: 2015-10-14, Last modification date: 2024-03-06)

Primary citation

Kung, D.W.,Griffith, D.A.,Esler, W.P.,Vajdos, F.F.,Mathiowetz, A.M.,Doran, S.D.,Amor, P.A.,Bagley, S.W.,Banks, T.,Cabral, S.,Ford, K.,Garcia-Irizarry, C.N.,Landis, M.S.,Loomis, K.,McPherson, K.,Niosi, M.,Rockwell, K.L.,Rose, C.,Smith, A.C.,Southers, J.A.,Tapley, S.,Tu, M.,Valentine, J.J.
Discovery of spirocyclic-diamine inhibitors of mammalian acetyl CoA-carboxylase.
Bioorg.Med.Chem.Lett., 25:5352-5356, 2015

PubMed Abstract: A novel series of spirocyclic-diamine based, isoform non-selective inhibitors of acetyl-CoA carboxylase (ACC) is described. These spirodiamine derivatives were discovered by design of a library to mimic the structural rigidity and hydrogen-bonding pattern observed in the co-crystal structure of spirochromanone inhibitor I. The lead compound 3.5.1 inhibited de novo lipogenesis in rat hepatocytes, with an IC50 of 0.30 μM.

PubMed: 26411795
DOI: 10.1016/j.bmcl.2015.09.035

Experimental method

X-RAY DIFFRACTION (2.7 Å)