Journal article
Structure-guided rescaffolding of selective antagonists of BCL-X L
MFT Koehler, P Bergeron, EF Choo, K Lau, C Ndubaku, D Dudley, P Gibbons, BE Sleebs, CS Rye, G Nikolakopoulos, C Bui, S Kulasegaram, WJA Kersten, BJ Smith, PE Czabotar, PM Colman, DCS Huang, JB Baell, KG Watson, L Hasvold Show all
ACS Medicinal Chemistry Letters | Published : 2014
DOI: 10.1021/ml500030p
Abstract
Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds. © 2014 American Chemical Society.
Grants
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Leukemia and Lymphoma Society
Awarded by Cancer Council of Victoria
Awarded by NHMRC Independent Research Institutes Infrastructure Support Scheme
Funding Acknowledgements
Part of this work was supported by fellowships and grants from the Australian Research Council (fellowship to P.E.C.), the National Health and Medical Research Council (NHMRC, fellowships to J.M.A., J.B.B., P.M.C., and D.C.S.H.; development grant 305536 and program grants 257502, 461221, and 1016701), the Leukemia and Lymphoma Society (specialized center of research grant nos. 7015 and 7413), the Cancer Council of Victoria (fellowship to P.M.C.; grant-in-aid 461239), and the Australian Cancer Research Foundation. Infrastructure support from the NHMRC Independent Research Institutes Infrastructure Support Scheme grant no. 361646 and a Victorian State Government OIS grant are gratefully acknowledged.