Target Enabling Packages (TEPs)

Overview

The Target Enabling Package (TEP) programme's foundation is built upon the recognition that genetic data is proving to be a powerful tool for target validation. As such, TEPs provide a critical mass of reagents and knowledge on a protein target to allow rapid biochemical and chemical exploration and characterisation of proteins with genetic linkage to key disease areas. TEPs provide an answer to the missing link between genomics and chemical biology, provide a starting point for chemical probe generation and therefore catalyse new biology and disease understanding with the ultimate aim of enabling translation collaborations and target/ drug discovery.

We are committed to generating and making available 27 high-quality TEPs by June 2020.

For more information regarding any aspect of TEPs and the TEP programme, please email at teps@thesgc.org.

Each TEP, as a minimum, contains:

  • Protein production methods
  • Biochemical/biophysical assays for activity, affinity
  • Structures of the protein, potentially including wild type and disease mutant proteins; full-length or domains; protein-ligand complexes; structures of close homologues
  • Initial chemical matter from a fragment or small molecule screen

Additional components of TEPs may be developed on a case-by-case basis, based upon reasonable scientific need, in collaboration with TEP target nominators:

  • An antibody or nanobody
  • Cell-based assay
  • CRISPR knockout
TEP Logo designed by Claire Strain-Damerell

Available TEPs

TEPs that have been approved by our external Evaluation Group are available via the links below.

Gene Description Therapeutic Area Version Date
ALAS2

Human 5'-Aminolevulinate synthase, erythoid-specific (ALAS2)

Metabolic diseases Version 1 2019
GALT/GALK1

Human Galactose- 1-phosphate uridylyltransferase (GALT)

Metabolic diseases Version 1 2019
KALRN/RAC1 Human Kalrin/RAC1 GEF/GTPase Complex (KARLN/RAC1) Neurological Disorders Version 1

2019

KEAP1

Human Kelch-like ECH Associated Protein 1 (KEAP1)

Neuropsychiatry Version 1 2019
KLHL20

Human Kelch-like protein 20 (KLHL20)

Cancer, Neuropsychiatry Version 1 2019
MLLT1 Human Mixed-Lineage Leukemia, Translocated to 1 (MLLT1) Cancer Version 1 2018
TASK1

Human TWIK-Related Acid-Sensitive K+ Channel 1 (TASK1)

Neurological Disorders Version 2 2019
TMEM16K

Human TMEM16K (ANO10)

Neurological Disorders Version 1 2019
HCN4 Human Hyperpolarization Activated Cyclic Nucleotide Gated Ion Channel 4 (HCN4) Cardiovascular, Inflammation, and Neuro Version 2 2018
NUDT7 Human Peroxisomal Coenzyme A Diphosphatase NUDT7 (NUDT7) Metabolic diseases Version 2 2018
PARP14 Human Poly (ADP-ribose) Polymerase Family Member 14 (PARP14) Cancer, Inflammation Version 1 2018
RIPK2 Human Receptor-Interacting Serine/Threonine-Protein Kinase 2 (RIPK2) Inflammatory diseases Version 2 2018
HAO1 Human Hydroxyacid Oxidase (HAO1) Metabolic disorders Version 2 2018
FAM83B Human Family With Sequence Similarity 83 Member B (FAM83B) Cancer Version 1 2018
LIMK1 Human LIM Domain Kinase 1 (LIMK1), Kinase Domain Neuropsychiatry Version 6 2017
DCLRE1A Human DNA Cross-Link Repair 1A (DCLRE1A, SNM1A) Cancer Version 5 2017
DPAGT1 Human Dolichyl-Phosphate Alpha-N-Acetyl glucosaminyl transferase (DPAGT1) Neuropsychiatry and neuro genetic disorders Version 4 2017
AASS Human Alpha-Aminoadipic Semialdehyde Synthase (AASS) Metabolic & Neurological disorders Version 6 2017
WNK3 Human With No Lysine Kinase 3 (WNK3) Metabolic diseases Version 6 2017
HDAC6 Human Histone Deacetylase 6 (HDAC6) Oncology Version 5 2016
KDM3B Lysine Demethylase JMJD1B (KDM3B) Cancer Version 5 2016
KDM4D Lysine Demethylase JMJD2D (KDM4D) Cancer Version 5 2016
PHIP Human Pleckstrin Homology Domain Interacting Protein (PHIP) Cancer Version 5 2016
PfBDP4 Plasmodium bormodomain PfBDP4 Malaria Version 5 2016
RECQL5 Human RECQL5 helicase Cancer Version 5 2016
SETDB1 Human SET domain bifurcated 1 (SETDB1), Tudor domain Oncology Version 6 2016
CDK12 Human Cyclin-Dependent Kinase 12 (CDK12), Kinase Domain Oncology Version 6 2016

The TEP Target List

The target list has been derived from nominations from both academia and industry with the expertise in key disease areas that are the focus of this programme: cancer, neuropsychiatry, inflammation, infectious diseases, metabolic disorders and rare diseases. Nominations are prioritised using the following criteria:

  • Robustness of available gene-disease association data
  • Significance of disease phenotype
  • Biological plausibility
  • Need for reagents to enable post-gene work (lack of structural and biochemical data)
  • Feasibility of producing a high quality TEP with our methodologies
  • Prospects for exploiting TEPs, such as existence of downstream communities or collaborators who are committed to using the TEP

Note that becuase the degree of genetic linkage with disease covers a broad spectrum ranging from monogenic (e.g. rare diseases, cancer) through to weaker polygenic (e.g. in some neurological diseases), we do not necessarily prioritise TEP targets based upon such linkages alone. Indeed, we may prioritise targets where there is weak linkage on the basis that TEP components would help to accelerate the understanding of the relevance of that linkage.

The current target list can be downloaded here.

How do I nominate targets as possible TEPs?

The SGC aims to promote exploration of new drug targets for treatment of human diseases in four broad therapeutic areas: Neuropsychiatry, Metabolic and other Rare diseases, Cancer, and Inflammation.

We are seeking nominations of new disease-linked genes, identified through genomic or gene expression research. We will then, possibly in collaboration with the nominating scientist, generate the purified proteins encoded by the disease-linked genes; functional assays; atomic-resolution structures; and chemical starting points. The data and reagents will be available to the wider research community, and in particular to our existing network of collaborators ranging from medicinal chemists to clinicians, which will ensure a rapid impact. 

Targets will be prioritised according to the following criteria:

  1. Robust disease link (Genetic or expression data)
  2. Plausible therapeutic hypothesis
  3. Need for tools (proteins, structures, assays, small molecules, antibodies)
  4. Prospects for collaborative research and downstream utilisation.

To nominate targets please download the Target nomination form and upload using the links below:

 Target nomination form (.xlsx)

How we generate and disseminate TEPs

We work closely with disease experts, clinicians, geneticists and industry experts in each of the key disease areas via our Target Prioritisation Networks (TPNs). These networks ensure that we prioritise our work on the targets which are most likely to lead to downstream utility once a TEP is released. The generation of the content of each TEP often directly involves collaborations with the nominator ensuring that that the TEP contains relevant and enabling reagents, data and knowledge.

Each TEP is carefully scrutinised by the TEP Evaluation Group, chaired by Prof. Mike Ferguson (Dundee), which makes the final decision on whether a TEP is suitable to be accepted for release to the public.

Our extensive network of partners and collaborators ensures that our TEPs are rapidly taken up and their contents used to study the biochemistry, structural and chemical biology of the target concerned.

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