Biomedical Engineering Reference
In-Depth Information
1.
Relatively low hit rates from resource - intensive high - throughput and
secondary screens with disproportionately few lead candidates that
maintain effi cacy in humans.
2.
Insuffi cient awareness among the researchers of the need to obtain very
domain specifi c biologically relevant chemical diversity [42].
3.
Academic and other nonprofi t laboratories focused on neglected
disease research tend to be distributed across the globe and in third
world/developed nations with limited opportunities or methods for
collaborations.
4.
Independent efforts, while providing signifi cant contributions, often lack
the project management, data handling, decision gates, and pipeline inte-
gration functions that are critical to effi cient drug development.
5.
Pharmaceutical company contributions are signifi cant but rarely shared
publicly.
A new approach is needed to speed up the drug discovery and development
process for neglected diseases. This could save millions of lives per year.
Foundations such as the Medicines for Malaria Ventures (MMV), the
Worldwide Anti-Malarial Resistance Network (WWARN), and TB Alliance
have recently become aware that a new paradigm of increased collaboration
is needed if new anti-infectives for neglected diseases are to become a reality.
These groups are effectively virtual drug discovery units that outsource all
aspects of preclinical and clinical research and act as a central point of orga-
nization. For example, MMV manages over 50 antimalarial projects in collabo-
ration with over 80 pharmaceutical, academic, and endemic-country partners
in 44 countries. TB Alliance has a similar role for TB drug discovery with over
20 on - going programs.
21.4.2 CDD TB DB and CDD Malaria DB as Examples of Community
Data Sharing and Evaluation
We have created separate networks of researchers in tuberculosis (well over
100 including TB Alliance and major laboratories in the United States and
Europe), in conjunction with the Bill and Melinda Gates Foundation (BMGF)
funding, and malaria (dozens) and kinetoplastids (dozens) from many of the
top laboratories. In an attempt to obtain a greater understanding of the chemi-
cal space of molecules tested against Mtb, we have created a Collaborative
Drug Discovery Tuberculosis Database (CDD TB) for related molecular
libraries of compounds from the literature [43]. CDD has collated at least 15
public data sets on Mtb-specifi c data sets representing well over 300,000 com-
pounds derived from patents, the literature, and high throughput screening
(HTS) data (Table 21.1). In addition, many major individual academic, non-
profi t, and commercial groups have used this Web-based database system [19]
to facilitate their own research and store and share their private data. To date
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