Biomedical Engineering Reference
In-Depth Information
TABLE 21.1.
(
Continued
)
Database Name/
Source
Description
Molecules
EthR inhibitors
Druglike inhibitors of transcriptional
repressor EthR; molecules and data from
Willand et al. [80]
5
Sacchettini review
First - and second - line anti - TB agents from
Tables 1 and 2 in Sacchettini et al. [81]
14
Makarov et al.,
NM4TB
consortia
SAR data for 1,3 - benzothiazin - 4 - ones
(BTZ); data obtained from Makarov et al.
[44] at NM4TB consortia
32
Small - molecule
patent data
Structures and patent information regarding
TB research from the U.S. Patent and
Trademark Offi ce, European Patent
Offi ce, and World Intellectual Property
Organization
20,775
Sacchettini review
additional
nonapproved
anti - TB drugs
Nonapproved anti-TB agents from Figure 1
in Sacchettini et al. [81]
18
Novartis TB data
Aerobic MTB activity (MIC
50
), anaerobic
MTB ATP activity (IC
50
), and cytotoxicity
(CC
50
) data
283
we have developed a unique community with over 20 pilot groups in the fi eld
of Mtb, including groups in the European Union (EU)-funded NM4TB initia-
tive [44] and groups funded by the BMGF tuberculosis accelerator project.
Our analysis of the public data sets [43] provided insights into molecular
properties and features that are determinants of activity in whole cells [43, 45].
This database has also been used to build novel computational machine learn-
ing and pharmacophore models that could be used to fi lter other libraries of
molecules to rapidly identify potential inhibitors [43, 45, 46].
CDD has also developed and deployed a robust preliminary public antima-
larial database from fi ve sources which hosts data on approximately 16,000
public compounds (Table 21.2). The growth of this database has fostered
several key antimalarial discovery collaborations between CDD users [19]. For
example, a substructure search for the known chemosensitizer substructure
led to the identifi cation of hundreds of compounds for laboratory evaluation
by the laboratories of Dr. Peter Smith in Cape Town to overcome the resis-
tance to chloroquine [19]. Leading candidates were identifi ed and sent from
collaborators for evaluation of effi cacy in assays using the resistant African
malarial parasite strains in human red blood cells. This process shaved months
off a project timeline relative to synthesizing new compounds from scratch.
Eighteen compounds were identifi ed from a set of U.S. Food and Drug
Administration (FDA)-approved drugs using substructure searching and half
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