navoximod   Click here for help

GtoPdb Ligand ID: 9019

Synonyms: GDC-0919 | NLG-919 | NLG919 | RG6078
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Navoximod (NLG-919) is a potent inhibitor of indoleamine-2,3-dioxygenase (IDO1) that was developed by Genentech and NewLink Genetics [2-3]. IOD1 is the first and rate-limiting component of the pathway mediating metabolism of tryptophan to kynurenine. Tryptophan depletion enhances the number and function of the Treg (suppressive) arm of the immune system and inhibits the effector T cell (stimulatory) arm. This action of IDO1 facilitates acquired local and peripheral immune tolerance in normal and pathological conditions. IOD1 inhibitors are being developed as novel therapeutics to reverse the immunosuppression associated with cancer.
The crystal structure of human IDO1 in complex with navoximod has been submitted to the PDB with ID 6O3I [2].
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

navoximod 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 2
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 38.05
Molecular weight 282.17
XLogP 4.14
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 OC(C1CCCCC1)CC1c2ccccc2c2n1cnc2
Isomeric SMILES OC(C1CCCCC1)CC1c2ccccc2c2n1cnc2
InChI InChI=1S/C18H22N2O/c21-18(13-6-2-1-3-7-13)10-16-14-8-4-5-9-15(14)17-11-19-12-20(16)17/h4-5,8-9,11-13,16,18,21H,1-3,6-7,10H2
InChI Key YTRRAUACYORZLX-UHFFFAOYSA-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. Dounay AB, Tuttle JB, Verhoest PR. (2015)
Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.
J Med Chem, 58 (22): 8762-82. [PMID:26207924]
2. Kumar S, Waldo JP, Jaipuri FA, Marcinowicz A, Van Allen C, Adams J, Kesharwani T, Zhang X, Metz R, Oh AJ et al.. (2019)
Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1.
J Med Chem, 62 (14): 6705-6733. [PMID:31264862]
3. Ma S, Suchomel J, Yanez E, Yost E, Liang X, Zhu R, Le H, Siebers N, Joas L, Morley R et al.. (2019)
Investigation of the absolute bioavailability and human mass balance of navoximod, a novel IDO1 inhibitor.
Br J Clin Pharmacol, 85 (8): 1751-1760. [PMID:30973970]
4. Nayak-Kapoor A, Hao Z, Sadek R, Dobbins R, Marshall L, Vahanian NN, Jay Ramsey W, Kennedy E, Mautino MR, Link CJ et al.. (2018)
Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors.
J Immunother Cancer, 6 (1): 61. [PMID:29921320]