Inhibitors of BCATm: A Tough Nut to Crack

Journal of Medicinal Chemistry

Volumn 58, Issue 18, 2015, Pages 7138-7139

  Scanlon, Martin ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; AMINOTRANSFERASE INHIBITOR; MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE; MITOCHONDRIAL BRANCHED CHAIN AMINOTRANSFERASE INHIBITOR; UNCLASSIFIED DRUG; MITOCHONDRIAL PROTEIN; PYRAZOLE DERIVATIVE; PYRIMIDINONE DERIVATIVE;

DRUG STRUCTURE; HIGH THROUGHPUT SCREENING; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; HUMAN;

ANIMALS; HUMANS; MITOCHONDRIAL PROTEINS; PYRAZOLES; PYRIMIDINONES; TRANSAMINASES;

EID: 84942274842     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01244     Document Type: Review

References (6)

1. Bertrand, S. M.; Ancellin, N.; Beaufils, B.; Bingham, R. P.; Borthwick, J. A.; Boullay, A.-B.; Boursier, E.; Carter, P. S.; Chung, C.-w.; Churcher, I.; Dodic, N.; Fouchet, M.-H.; Fournier, C.; Francis, P. L.; Gummer, L. A.; Herry, K.; Hobbs, A.; Hobbs, C. I.; Homes, P.; Jamieson, C.; Nicodeme, E.; Pickett, S. D.; Reid, I. H.; Simpson, G. L.; Sloan, L. A.; Smith, S. E.; Somers, D. O.; Spitzfaden, C.; Suckling, C. J.; Valko, K.; Washio, Y.; Young, R. J. The Discovery of in Vivo Active Mitochondrial Branched-Chain Aminotransferase (BCATm) Inhibitors by Hybridizing Fragment and HTS Hits J. Med. Chem. 2015, 10.1021/acs.jmedchem.5b00313
2. She, P.; Reid, T. M.; Bronson, S. K.; Vary, T. C.; Hajnal, A.; Lynch, C. J.; Hutson, S. M. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle Cell Metab. 2007, 6 (3) 181-94 10.1016/j.cmet.2007.08.003
3. Hopkins, A. L.; Keseru, G. M.; Leeson, P. D.; Rees, D. C.; Reynolds, C. H. The role of ligand efficiency metrics in drug discovery Nat. Rev. Drug Discovery 2014, 13 (2) 105-21 10.1038/nrd4163
4. Shultz, M. D. Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters Bioorg. Med. Chem. Lett. 2013, 23 (21) 5980-91 10.1016/j.bmcl.2013.08.029
5. Arrowsmith, C. H.; Audia, J. E.; Austin, C.; Baell, J.; Bennett, J.; Blagg, J.; Bountra, C.; Brennan, P. E.; Brown, P. J.; Bunnage, M. E.; Buser-Doepner, C.; Campbell, R. M.; Carter, A. J.; Cohen, P.; Copeland, R. A.; Cravatt, B.; Dahlin, J. L.; Dhanak, D.; Edwards, A. M.; Frye, S. V.; Gray, N.; Grimshaw, C. E.; Hepworth, D.; Howe, T.; Huber, K. V.; Jin, J.; Knapp, S.; Kotz, J. D.; Kruger, R. G.; Lowe, D.; Mader, M. M.; Marsden, B.; Mueller-Fahrnow, A.; Muller, S.; OHagan, R. C.; Overington, J. P.; Owen, D. R.; Rosenberg, S. H.; Roth, B.; Ross, R.; Schapira, M.; Schreiber, S. L.; Shoichet, B.; Sundstrom, M.; Superti-Furga, G.; Taunton, J.; Toledo-Sherman, L.; Walpole, C.; Walters, M. A.; Willson, T. M.; Workman, P.; Young, R. N.; Zuercher, W. J. The promise and peril of chemical probes Nat. Chem. Biol. 2015, 11 (8) 536-541 10.1038/nchembio.1867
6. Deng, H.; Zhou, J.; Sundersingh, F. S.; Summerfield, J.; Somers, D.; Messer, J. A.; Satz, A. L.; Ancellin, N.; Arico-Muendel, C. C.; Bedard, K. L.; Beljean, A.; Belyanskaya, S. L.; Bingham, R.; Smith, S. E.; Boursier, E.; Carter, P.; Centrella, P. A.; Clark, M. A.; Chung, C.-w.; Davie, C. P.; Delorey, J. L.; Ding, Y.; Franklin, G. J.; Grady, L. C.; Herry, K.; Hobbs, C.; Kollmann, C. S.; Morgan, B. A.; Kaushansky, L. J.; Zhou, Q. Discovery, SAR, and X-ray Binding Mode Study of BCATm Inhibitors from a Novel DNA-Encoded Library ACS Med. Chem. Lett. 2015, 6, 919-924 10.1021/acsmedchemlett.5b00179