TY - JOUR
T1 - From hit seeking to magic bullets: The successful union of epigenetic and fragment based drug discovery (EPIDD + FBDD)
AU - Vaidergorn, Miguel M.
AU - da Silva Emery, Flavio
AU - Ganesan, A.
N1 - Funding Information: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES), Finance Code 001, by São Paulo Research Foundation (FAPESP) Grant No. 2013/50677-7 and 2017/21146-4, and by the National Council for Scientific and Technological Development (CNPq) Grant No. 313834/2018-0.
PY - 2021/10/14
Y1 - 2021/10/14
N2 - We review progress in the application of fragment-based drug discovery (FBDD) to epigenetic drug discovery (EPIDD) targeted at epigenetic writer and eraser enzymes as well as reader domains over the last 15 years. The greatest successes to date are in prospecting for bromodomain binding ligands. From a diverse array of fragment hits, multiple potent and selective compounds ensued, including the oncology clinical candidates mivebresib, ABBV-744, pelabresib, and PLX51107.
AB - We review progress in the application of fragment-based drug discovery (FBDD) to epigenetic drug discovery (EPIDD) targeted at epigenetic writer and eraser enzymes as well as reader domains over the last 15 years. The greatest successes to date are in prospecting for bromodomain binding ligands. From a diverse array of fragment hits, multiple potent and selective compounds ensued, including the oncology clinical candidates mivebresib, ABBV-744, pelabresib, and PLX51107.
UR - http://www.scopus.com/inward/record.url?scp=85117141816&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.1c00787
DO - 10.1021/acs.jmedchem.1c00787
M3 - Article
VL - 64
SP - 13980
EP - 14010
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 19
ER -