enpatoran   Click here for help

GtoPdb Ligand ID: 11307

Synonyms: compound 73 [WO2017106607A1] | M-5049 | M5049
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: This chemical structure (as the IUPAC name) was obtained from the special release of proposed INNs for COVID-related therapeutics that was published by the WHO in October 2020. The INN structure was identified as being identical to compound 73 from Merck's patent WO2017106607A1 (2017) in which it is claimed as a Toll-like receptor (TLR)7 and TLR8 antagonist for the treatment of immune disorders [3]. We speculated that this was Merck's clinical lead M5049, which is expected to prevent activation of TLR7/8 which detect single-stranded RNA from viruses including SARS-CoV-2 [1]. M5049 is administered orally. Name-to-structure was confirmed in spring 2021 [4]. The structure of M5049 was subsequently matched to the INN enpatoran.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

enpatoran is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 65.94
Molecular weight 320.12
XLogP 3.24
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES N#Cc1ccc(c2c1nccc2)N1C[C@H](N)C[C@@H](C1)C(F)(F)F
Isomeric SMILES N#Cc1ccc(c2c1nccc2)N1C[C@H](N)C[C@@H](C1)C(F)(F)F
InChI InChI=1S/C16H15F3N4/c17-16(18,19)11-6-12(21)9-23(8-11)14-4-3-10(7-20)15-13(14)2-1-5-22-15/h1-5,11-12H,6,8-9,21H2/t11-,12+/m0/s1
InChI Key BJXYHBKEQFQVES-NWDGAFQWSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Merck. 
Merck Initiates First Clinical Trial of TLR7 and 8 Inhibitor as a Potential Treatment for Severe Symptoms of Covid-19 Infection.
Accessed on 02/11/2020. Modified on 02/11/2020. www.merckgroup.com, https://www.merckgroup.com/en/news/m5049-treatment-covid-19-pneumonia.html
2. Port A, Shaw JV, Klopp-Schulze L, Bytyqi A, Vetter C, Hussey E, Mammasse N, Ona V, Bachmann A, Strugala D et al.. (2021)
Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8.
Pharmacol Res Perspect, 9 (5): e00842. [PMID:34414672]
3. Sherer BA, Brugger N. (2017)
Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders.
Patent number: WO2017106607A1. Assignee: Merck Patent Gmbh. Priority date: 17/12/2015. Publication date: 22/06/2017.
4. Vlach J, Bender AT, Przetak M, Pereira A, Deshpande A, Johnson TL, Reissig S, Tzvetkov E, Musil D, Morse NT et al.. (2021)
Discovery of M5049: A Novel Selective Toll-Like Receptor 7/8 Inhibitor for Treatment of Autoimmunity.
J Pharmacol Exp Ther, 376 (3): 397-409. [PMID:33328334]