Structural highlights
8qh9 is a 1 chain structure with sequence from Danio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 1.59Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
F8W4B7_DANRE
Publication Abstract from PubMed
Our previously reported HDAC6 inhibitor (HDAC6i) Marbostat-100 (4) has provided many arguments for further clinical evaluation. By the substitution of the acidic hydrogen of 4 for different carbon residues, we were able to generate an all-carbon stereocenter, which significantly improves the hydrolytic stability of the inhibitor. Further asymmetric synthesis has shown that the (S)-configured inhibitors preferentially bind to HDAC6. This led to the highly selective and potent methyl-substituted derivative S-29b, which elicited a long-lasting tubulin hyperacetylation in MV4-11 cells. Finally, a crystal structure of the HDAC6/S-29b complex provided mechanistic explanation for the high potency and stereoselectivity of synthesized compound series.
Biological and structural investigation of tetrahydro-beta-carboline-based selective HDAC6 inhibitors with improved stability.,Scheuerer S, Motlova L, Schaker-Hubner L, Sellmer A, Feller F, Ertl FJ, Koch P, Hansen FK, Barinka C, Mahboobi S Eur J Med Chem. 2024 Jul 26;276:116676. doi: 10.1016/j.ejmech.2024.116676. PMID:39067437[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Scheuerer S, Motlova L, Schäker-Hübner L, Sellmer A, Feller F, Ertl FJ, Koch P, Hansen FK, Barinka C, Mahboobi S. Biological and structural investigation of tetrahydro-β-carboline-based selective HDAC6 inhibitors with improved stability. Eur J Med Chem. 2024 Jul 26;276:116676. PMID:39067437 doi:10.1016/j.ejmech.2024.116676
