Now showing items 1-7 of 7

    • 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19. 

      Mallinger, A; Schiemann, K; Rink, C; Sejberg, J; Honey, MA; Czodrowski, P; Stubbs, M; Poeschke, O; Busch, M; Schneider, R; Schwarz, D; Musil, D; Burke, R; Urbahns, K; Workman, P; Wienke, D; Clarke, PA; Raynaud, FI; Eccles, SA; Esdar, C; Rohdich, F; Blagg, J (2016-06)
      We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid ...
    • Assessing histone demethylase inhibitors in cells: lessons learned. 

      Hatch, SB; Yapp, C; Montenegro, RC; Savitsky, P; Gamble, V; Tumber, A; Ruda, GF; Bavetsias, V; Fedorov, O; Atrash, B; Raynaud, F; Lanigan, R; Carmichael, L; Tomlin, K; Burke, R; Westaway, SM; Brown, JA; Prinjha, RK; Martinez, ED; Oppermann, U; Schofield, CJ; Bountra, C; Kawamura, A; Blagg, J; Brennan, PE; Rossanese, O; Müller, S (2017)
      BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ...
    • Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy. 

      Faisal, A; Mak, GWY; Gurden, MD; Xavier, CPR; Anderhub, SJ; Innocenti, P; Westwood, IM; Naud, S; Hayes, A; Box, G; Valenti, MR; De Haven Brandon, AK; O'Fee, L; Schmitt, J; Woodward, HL; Burke, R; vanMontfort, RLM; Blagg, J; Raynaud, FI; Eccles, SA; Hoelder, S; Linardopoulos, S (2017-04-25)
      BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ...
    • Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells. 

      Rodgers, UR; Lanyon-Hogg, T; Masumoto, N; Ritzefeld, M; Burke, R; Blagg, J; Magee, AI; Tate, EW (2016-12-16)
      The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ...
    • Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates. 

      Liu, M; Mallinger, A; Tortorici, M; Newbatt, Y; Richards, M; Mirza, A; van Montfort, RLM; Burke, R; Blagg, J; Kaserer, T (2018-09-21)
      APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate ...
    • Privileged Structures and Polypharmacology within and between Protein Families. 

      Meyers, J; Chessum, NEA; Ali, S; Mok, NY; Wilding, B; Pasqua, AE; Rowlands, M; Tucker, MJ; Evans, LE; Rye, CS; O'Fee, L; Le Bihan, Y-V; Burke, R; Carter, M; Workman, P; Blagg, J; Brown, N; van Montfort, RLM; Jones, K; Cheeseman, MD (2018-12-13)
      Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ...
    • Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach. 

      Innocenti, P; Woodward, HL; Solanki, S; Naud, S; Westwood, IM; Cronin, N; Hayes, A; Roberts, J; Henley, AT; Baker, R; Faisal, A; Mak, GW; Box, G; Valenti, M; De Haven Brandon, A; O'Fee, L; Saville, H; Schmitt, J; Matijssen, B; Burke, R; van Montfort, RL; Raynaud, FI; Eccles, SA; Linardopoulos, S; Blagg, J; Hoelder, S (2016-04-07)
      Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ...