PMID- 24900343
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140605
LR  - 20211021
IS  - 1948-5875 (Print)
IS  - 1948-5875 (Electronic)
IS  - 1948-5875 (Linking)
VI  - 2
IP  - 7
DP  - 2011 Jul 14
TI  - Chemical transformations that yield compounds with distinct activity profiles.
PG  - 523-7
LID - 10.1021/ml2000609 [doi]
AB  - We have systematically searched for chemical changes that generate compounds with 
      distinct biological activity profiles. For this purpose, activity profiles were 
      generated for  approximately 42000 compounds active against human targets. Unique activity 
      profiles involving multiple target proteins were determined, and all possible 
      matched molecular pairs (MMPs) were identified for compounds representing these 
      profiles. An MMP is defined as a pair of compounds that are distinguished from 
      each other only at a single site such as an R group or ring system. For example, 
      in an MMP, a hydroxyl group might be replaced by a halogen atom or a benzene ring 
      by an amide group. From  approximately 37500 MMPs, more than 300 nonredundant chemical 
      transformations were isolated that yielded compounds with distinct activity 
      profiles. None of these transformations was found in pairs of compounds with 
      overlapping activity profiles. These transformations were ranked according to the 
      number of MMPs, the number of activity profiles, and the total number of targets 
      that they covered. In many instances, prioritized transformations involved ring 
      systems of varying complexity. All transformations that were found to switch 
      activity profiles are provided to enable further analysis and aid in compound 
      design efforts.
FAU - Hu, Ye
AU  - Hu Y
AD  - Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology 
      and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universitat , 
      Dahlmannstrasse 2, D-53113 Bonn, Germany.
FAU - Bajorath, Jurgen
AU  - Bajorath J
AD  - Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology 
      and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universitat , 
      Dahlmannstrasse 2, D-53113 Bonn, Germany.
LA  - eng
PT  - Journal Article
DEP - 20110413
PL  - United States
TA  - ACS Med Chem Lett
JT  - ACS medicinal chemistry letters
JID - 101521073
PMC - PMC4018055
OTO - NOTNLM
OT  - Active compounds
OT  - activity profiles
OT  - chemical transformations
OT  - matched molecular pairs
OT  - profile analysis
OT  - target annotations
EDAT- 2011/07/14 00:00
MHDA- 2011/07/14 00:01
PMCR- 2012/07/14
CRDT- 2014/06/06 06:00
PHST- 2011/02/24 00:00 [received]
PHST- 2011/04/13 00:00 [accepted]
PHST- 2014/06/06 06:00 [entrez]
PHST- 2011/07/14 00:00 [pubmed]
PHST- 2011/07/14 00:01 [medline]
PHST- 2012/07/14 00:00 [pmc-release]
AID - 10.1021/ml2000609 [doi]
PST - epublish
SO  - ACS Med Chem Lett. 2011 Apr 13;2(7):523-7. doi: 10.1021/ml2000609. eCollection 
      2011 Jul 14.