Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1205 - 1214 |
| Number of pages | 10 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 58 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2015 |
Cite this
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Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold. / Devine, Shane; Mulcair, Mark; Debono, Cael; Leung, Eleanor Wai Wai; Nissink, J Willem M; Lim, San Sui; Chandrashekaran, Indu Rajmohan; Vazirani, Mansha; Mohanty, Biswaranjan; Simpson, Jamie Scott; Baell, Jonathan Bayldon; Scammells, Peter John; Norton, Raymond Stanley; Scanlon, Martin.
In: Journal of Medicinal Chemistry, Vol. 58, No. 3, 2015, p. 1205 - 1214.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold
AU - Devine, Shane
AU - Mulcair, Mark
AU - Debono, Cael
AU - Leung, Eleanor Wai Wai
AU - Nissink, J Willem M
AU - Lim, San Sui
AU - Chandrashekaran, Indu Rajmohan
AU - Vazirani, Mansha
AU - Mohanty, Biswaranjan
AU - Simpson, Jamie Scott
AU - Baell, Jonathan Bayldon
AU - Scammells, Peter John
AU - Norton, Raymond Stanley
AU - Scanlon, Martin
PY - 2015
Y1 - 2015
N2 - We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a diverse range of protein targets, suggesting that this scaffold is a poor starting point for fragment-based drug discovery. This prompted us to analyze this scaffold in the context of an academic fragment library used for fragment-based drug discovery (FBDD) and two larger compound libraries used for high-throughput screening (HTS). This analysis revealed that such promiscuous 2-aminothiazoles (PrATs) behaved as frequent hitters under both FBDD and HTS settings, although the problem was more pronounced in the fragment-based studies. As 2-ATs are present in known drugs, they cannot necessarily be deemed undesirable, but the combination of their promiscuity and difficulties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds for fragment libraries.
AB - We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a diverse range of protein targets, suggesting that this scaffold is a poor starting point for fragment-based drug discovery. This prompted us to analyze this scaffold in the context of an academic fragment library used for fragment-based drug discovery (FBDD) and two larger compound libraries used for high-throughput screening (HTS). This analysis revealed that such promiscuous 2-aminothiazoles (PrATs) behaved as frequent hitters under both FBDD and HTS settings, although the problem was more pronounced in the fragment-based studies. As 2-ATs are present in known drugs, they cannot necessarily be deemed undesirable, but the combination of their promiscuity and difficulties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds for fragment libraries.
UR - http://pubs.acs.org/doi/pdf/10.1021/jm501402x
U2 - 10.1021/jm501402x
DO - 10.1021/jm501402x
M3 - Article
VL - 58
SP - 1205
EP - 1214
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 3
ER -