TY  - JOUR
A1  - Zaienne, Daniel
A1  - Arifi, Silvia
A1  - Marschner, Julian
A1  - Heering, Jan Peter
A1  - Merk, Daniel
T1  - Druggability Evaluation of the Neuron Derived Orphan Receptor (NOR-1) Reveals Inverse NOR-1 Agonists
T2  - ChemMedChem
N2  - The neuron derived orphan receptor (NOR-1, NR4A3) is among the least studied nuclear receptors. Its physiological role and therapeutic potential remain widely elusive which is in part due to the lack of chemical tools that can directly modulate NOR-1 activity. To probe the possibility of pharmacological NOR-1 modulation, we have tested a drug fragment library for NOR-1 activation and repression. Despite low hit-rate (<1 %), we have obtained three NOR-1 ligand chemotypes one of which could be rapidly expanded to an analogue comprising low micromolar inverse NOR-1 agonist potency and altering NOR-1 regulated gene expression in a cellular setting. It confirms druggability of the transcription factor and may serve as an early tool to assess the role and potential of NOR-1.
KW  - NR4A3
KW  - transcription factor
KW  - nuclear receptor
KW  - neurodegeneration
KW  - fragment screening
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73525
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-735252
SN  - 1860-7187
N1  - This research was financially supported by the Aventis Foundation (Life Science Bridge Award to D.M.). This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under Grant Agreement No. 875510. The JU received support from the European Union's Horizon 2020 research and innovation programme and EFPIA and Ontario Institute for Cancer Research, Royal Institution for the Advancement of Learning McGill University, Kungliga Tekniska Hoegskolan, Diamond Light Source Limited. Gal4-VP16 was a gift from Lea Sistonen (Addgene plasmid #71728). Open Access funding enabled and organized by Projekt DEAL.
VL  - 17
IS  - 16, art. e202200259
SP  - 1
EP  - 5
PB  - Wiley-VCH
CY  - Weinheim
ER  -