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ACT-389949   Click here for help

GtoPdb Ligand ID: 9511

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: ACT-389949 is a novel potent and selective FPR2/ALX agonist [13]. Results from Phase 1 trials in healthy subjects show that ACT-389949 is well tolerated, but drug potential is hampered by several factors: it causes rapid receptor desensitisation; it elicits only a transient response; biomarker analysis suggests that the response is pro-inflammatory rather than anti-inflammatory [13].
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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.

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View interactive charts of activity data across species

ACT-389949 is commercially available from our sponsors

2D Structure
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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.

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Click here for structure editor
Physico-chemical Properties
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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.

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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 111.87
Molecular weight 428.14
XLogP 3.72
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
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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/)

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Canonical SMILES Cc1cccc(c1)c1oc(nc1C(=O)Nc1cnn(n1)Cc1occ(n1)C(F)(F)C)C
Isomeric SMILES Cc1cccc(c1)c1oc(nc1C(=O)Nc1cnn(n1)Cc1occ(n1)C(F)(F)C)C
InChI InChI=1S/C20H18F2N6O3/c1-11-5-4-6-13(7-11)18-17(24-12(2)31-18)19(29)26-15-8-23-28(27-15)9-16-25-14(10-30-16)20(3,21)22/h4-8,10H,9H2,1-3H3,(H,26,27,29)
InChI Key PBTWPEDVIMHJEO-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. Clish CB, O'Brien JA, Gronert K, Stahl GL, Petasis NA, Serhan CN. (1999)
Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo.
Proc Natl Acad Sci USA, 96 (14): 8247-52. [PMID:10393980]
2. Fiore S, Maddox JF, Perez HD, Serhan CN. (1994)
Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor.
J Exp Med, 180 (1): 253-60. [PMID:8006586]
3. Fiore S, Serhan CN. (1995)
Lipoxin A4 receptor activation is distinct from that of the formyl peptide receptor in myeloid cells: inhibition of CD11/18 expression by lipoxin A4-lipoxin A4 receptor interaction.
Biochemistry, 34 (51): 16678-86. [PMID:8527441]
4. Gabl M, Sundqvist M, Holdfeldt A, Lind S, Mårtensson J, Christenson K, Marutani T, Dahlgren C, Mukai H, Forsman H. (2018)
Mitocryptides from Human Mitochondrial DNA-Encoded Proteins Activate Neutrophil Formyl Peptide Receptors: Receptor Preference and Signaling Properties.
J Immunol, 200 (9): 3269-3282. [PMID:29602776]
5. García RA, Lupisella JA, Ito BR, Hsu MY, Fernando G, Carson NL, Allocco JJ, Ryan CS, Zhang R, Wang Z et al.. (2021)
Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction.
JACC Basic Transl Sci, 6 (8): 676-689. [PMID:34466754]
6. Gronert K, Martinsson-Niskanen T, Ravasi S, Chiang N, Serhan CN. (2001)
Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.
Am J Pathol, 158 (1): 3-9. [PMID:11141472]
7. Le Y, Gong W, Li B, Dunlop NM, Shen W, Su SB, Ye RD, Wang JM. (1999)
Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation.
J Immunol, 163 (12): 6777-84. [PMID:10586077]
8. Lin H, Ma C, Cai K, Guo L, Wang X, Lv L, Zhang C, Lin J, Zhang D, Ye C et al.. (2025)
Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis.
Science, 388 (6746): eado4188. [PMID:40080544]
9. Peng C, Vecchio EA, Nguyen ATN, De Seram M, Tang R, Keov P, Woodman OL, Chen YC, Baell J, May LT et al.. (2024)
Biased receptor signalling and intracellular trafficking profiles of structurally distinct formylpeptide receptor 2 agonists.
Br J Pharmacol, 181 (22): 4677-4692. [PMID:39154373]
10. Perretti M, Flower RJ. (1995)
Anti-inflammatory lipocortin-derived peptides.
Agents Actions Suppl, 46: 131-8. [PMID:7610983]
11. Qin CX, May LT, Li R, Cao N, Rosli S, Deo M, Alexander AE, Horlock D, Bourke JE, Yang YH et al.. (2017)
Small-molecule-biased formyl peptide receptor agonist compound 17b protects against myocardial ischaemia-reperfusion injury in mice.
Nat Commun, 8: 14232. [PMID:28169296]
12. Rabiet MJ, Huet E, Boulay F. (2005)
Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR.
Eur J Immunol, 35 (8): 2486-95. [PMID:16025565]
13. Stalder AK, Lott D, Strasser DS, Cruz HG, Krause A, Groenen PM, Dingemanse J. (2017)
Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949.
Br J Clin Pharmacol, 83 (3): 476-486. [PMID:27730665]
14. Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN. (1997)
Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors.
J Exp Med, 185 (9): 1693-704. [PMID:9151906]