The Structure-guided Drug Discovery Coalition (SDDC) comprises the Seattle Structural Genomics Center for Infectious Disease (SSGCID), the Midwest Center for Structural Genomics, the Center for Structural Genomics of Infectious Diseases (CSGID), and drug discovery teams from academia and industry has resulted in 7 early drug leads for tuberculosis (TB), malaria, and cryptosporidiosis. The SDDC receives funding from participating academic initiatives and the Bill & Melinda Gates Foundation.
The University of North Carolina at Chapel Hill and the Eshelman Institute for Innovation, launched Rapidly Emerging Antiviral Drug Development Initiative (READDI™) and Viral Interruption to Medicines Initiative (VIMI™). REDDI™ is modelled after the non-profit drug research and development Drugs for Neglected Diseases Initiative (DNDi). READDI™ and VIMI™ are non-profit, open science initiatives that focus on developing therapeutics for all pandemic-capable viruses.
The for-profit spin-off companies M4K Pharma (Medicines for Kids), M4ND Pharma (Medicines for Neurological Diseases) and M4ID Pharma (Medicines for Infectious Diseases) do not file patents and practise open science. The M4 companies are wholly owned by a Canadian charity Agora Open Science Trust whose mandate is to share scientific knowledge and ensure affordable access to all medicines. M4K Pharma has the most advanced open drug discovery program and is supported with funding from the Ontario Institute for Cancer Research, The Brain Tumour Charity, Charles River Laboratories and Reaction Biology, and with contributions from scientists at the Universities of McGill, North Carolina, Oxford, Pennsylvania, and Toronto and in the Sant Joan de Déu hospital, the University Health Network hospitals, the Hospital for Sick Children, and The Institute for Cancer Research. M4K Pharma is developing a selective inhibitor of ALK2 for DIPG, a uniformly fatal pediatric brain tumour.
In 2000, a group of companies and Wellcome conceptualized forming a Structural Genomics Consortium to focus on determining the three-dimensional structures of human proteins. The consortium must place all structural information and supporting reagents into the public domain without restriction. This effort was designed to complement other structural genomics programs in the world.
The SGC scientific program was launched, with activities at the Universities of Oxford and Toronto, and with a mandate to contribute >350 human protein structures into the public domain. To be counted toward these goals, the proteins had to derive from a pre-defined list and the protein structures were required to meet pre-defined quality criteria. The quality of protein structures was and continues to be adjudicated by a committee of independent academic scientists. Michael Morgan was the Chair of the SGC Board, and the scientific activities were led by Cheryl Arrowsmith (Toronto) and Michael Sundstrom (Oxford). In mid 2005, VINNOVA, the Knut and Alice Wallenberg Foundation and the Foundation for Strategic Research (SSF) established the Swedish research node of the SGC. Experimental activities started at the Karolinska Institutet in Stockholm, led by Pär Nordlund and Johan Weigelt. Together, the three SGC laboratories contributed 392 human protein structures into the public domain. A pilot program in the structural biology of proteins in the malaria parasite was also initiated.
The new goal for structures was 650. The SGC focused considerable activities in the areas of ubiquitination, protein phosphorylation, small G-proteins and epigenetics, and also initiated an effort in the structural biology of integral membrane proteins. In this phase, the SGC determined the structures of 665 human proteins from its Target List. With support from Wellcome and GSK, the SGC launched a program to develop freely-available chemical probes to proteins involved in epigenetic signalling which at the time were under studied. The quality of each chemical probe was subject to two levels of review prior to their dissemination to the public. The first was internal, through a Joint Management Committee comprising representatives from each member organization. The second was provided by a group of independent experts selected from academia. This level of oversight is aimed at developing reagents that support reproducible research. It ultimately led to the creation of the Chemical Probes Portal. The SGC Memberships expanded to include Merck, Sharpe and Dohme, and Novartis. Wayne Hendrickson served as the Chair of the SGC Board.
The SGC mandate diversified to include 200 human proteins including 5 integral membrane proteins and chemical probes (30). Many of the chemical probes’ programs were undertaken in partnership with scientists in the pharmaceutical companies, which made the commitment to contribute the collaborative chemical probe into the public domain, without restriction. In Phase III, the SGC, along with the SSGCID (https://www.ssgcid.org/) and the CSGID (https://csgid.org/) launched the SDDC.
SGC Memberships: AbbVie, Bayer AG, Boehringer Ingelheim, Eli Lilly and Janssen. Merck, Sharpe and Dohme and the Canadian Institutes for Health Research left the consortium. Markus Gruetter became the Chair of the SGC Board.
This phase built on the goals of previous phases but included well-characterized antibodies to human proteins. The SGC initiated a concerted effort to develop disease-relevant, cell-based assays using (primary) cells or tissue from patients. This phase saw the launch of research activities at Goethe University in Frankfurt, at McGill University, and at the Universities of Campinas and North Carolina, and participation in ULTRADD and RESOLUTE within IMI.
SGC Memberships: Merck KGaA, the Eshelman Institute for Innovation, Merck, Sharpe and Dohme joined while GSK and Eli Lilly left. Tetsuyuki Maruyama became the Chair of the Board.
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