Target 2035 is a global effort or movement to discover open science,

pharmacological Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

modulator(s) for every protein in the human proteome by the year 2035. The effort is led by the

Structural Genomics Consortium The Structural Genomics Consortium (SGC) is a public-private-partnership focusing on elucidating the functions and disease relevance of all proteins encoded by the human genome, with an emphasis on those that are relatively understudied. The SGC pl ...

with the intention that this movement evolves organically. Target 2035 has been borne out of the success that

chemical probe In the field of chemical biology, a chemical probe is a small molecule that is used to study and manipulate a biological system such as a cell or an organism by reversibly binding to and altering the function of a biological target (most commonly ...

s have had in elevating or de-prioritizing the therapeutic potential of protein targets. The availability of

open access Open access (OA) is a set of principles and a range of practices through which research outputs are distributed online, free of access charges or other barriers. With open access strictly defined (according to the 2001 definition), or libre op ...

pharmacological tools is a largely unmet aspect of

drug discovery In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...

especially for the dark proteome. The first five years will include building mechanisms (Phase 1 below) which allow researchers to find collaborators with like-minded goals towards discovering a

tool for a specific protein or protein family, and make it open access (without encumbrances due to intellectual property). One strategic goal is seeding new open science programs on components of the

pipeline with the goal to bring medicines to the bedside equitably, affordably and rapidly. Phase 1 will also build a framework that welcomes new and (re-)emerging enabling technologies in hit-finding and characterization. An update on the progress was published. Target 2035 will draw on successes from past and current publicly-funded programs including

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

(NIH
Illuminating the Druggable Genome initiative
for under-explored kinases, GPCR’s and

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

Innovative Medicines Initiative The Innovative Medicines Initiative (IMI) is a European initiative to improve the competitive situation of the European Union in the field of pharmaceutical research. The IMI is a joint initiative ( public-private partnership) of the DG Researc ...

'
RESOLUTE
project on human SLCs,

'
Enabling and Unlocking Biology in the Open
(EUbOPEN), and

'
Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery
The NIH recently re-iterated their commitment to making their data open to mitigate the tens of billions due to irreproducible data. Target 2035 will collaborate with the

Chemical Probes Portal The Chemical Probes Portal is an open, online resource whose purpose is to identify and make available high quality chemical probes for use in biological research and drug discovery. While chemical probes can be valuable tools to elucidate sig ...

and open science platforms, e.g
Just One Giant Lab
in order to spread awareness and education of best practices for chemical modulators and the benefits of open science, respectively. The following draft plan has been outlined in a white paper.

Phase 1

The first phase, from 2020 to 2025, would be structured to build the foundation for a concerted global effort, and would aim to collect, characterize and make available existing pharmacological modulators for key representatives from all proteins families in the current druggable genome (~4,000 proteins), as well as to develop critical and centralized infrastructure to facilitate data collection, curation, dissemination, and mining that will power the scientific community worldwide. This phase might also create centralized facilities to provide quantitative genome-scale biochemical and cell-based profiling assays to the federated community, as well as to coordinate the development of new technologies to extend the definition of druggability. This first phase will complement and extend ongoing efforts to create chemical tools and chemogenomic libraries to blanket priority gene families, such as kinases and epigenetics families. One year into Target 2035 has so far yielded infrastructure to hous
data
on chemogenomic compounds reported in the literature. A progress update was published recently. Towards the development of new technologies, Target 2035 started a new initiativ
Critical Assessment of Computational Hit-Finding Experiments
(CACHE) aimed at benchmarking computational methods for hit-finding. The firs
competition
- finding ligands for the WD40 domain of LRRK2 - started in March 2022. The first round of predictions have been submitted. In the meantime, applications for the second CACHE benchmarking
predicting ligands for the RNA-binding domain for Nsp13
- has been posted.

Phase 2

The second phase, from 2025 to 2035, will be to apply the new technologies and infrastructure to generate a complete set of pharmacological modulators for > 90% of the ~20,000 proteins encoded by the genome. “Target 2035” sounds ambitious, but its concept and practicality is on firm ground based on a number of pilot studies, which revealed the following success parameters: * Collaborate with the pharmaceutical sector to access unparalleled expertise, experience, materials, and logistics * Establish clear and quantitative quality criteria for the output (target chemical tool profiles) to provide focus * Organize the project around protein families – it is the most efficient, practical and scientifically sound way to divide this large project into teams * Establish clear open science principles to eliminate or reduce conflicts of interest, to reduce legal encumbrances, and to encourage participation by the community.

References

External links

* {{Official, https://www.target2035.net/ Drug discovery Open science Chemical biology