praliciguat   Click here for help

GtoPdb Ligand ID: 9900

Synonyms: IW-1973 | IW1973
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Praliciguat (IW-1973) is a potent, orally available soluble guanylyl cyclase (sGC) stimulator [3]. sGC stimulators/activators have potential as heart failure therapeutics [1]. Praliciguat exhibits anti-hypertensive, reno-protective, anti-fibrotic effects and anti-inflammatory activities. Effects observed in renal fibrosis models suggests potential for the treatment of diabetic nephropathy.
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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

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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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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 5
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 101.89
Molecular weight 534.11
XLogP 5.42
No. Lipinski's rules broken 1

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 Fc1cnc(nc1NCC(C(F)(F)F)(C(F)(F)F)O)c1nn(c(c1)c1nocc1)Cc1ccccc1F
Isomeric SMILES Fc1cnc(nc1NCC(C(F)(F)F)(C(F)(F)F)O)c1nn(c(c1)c1nocc1)Cc1ccccc1F
InChI InChI=1S/C21H14F8N6O2/c22-12-4-2-1-3-11(12)9-35-16(14-5-6-37-34-14)7-15(33-35)18-30-8-13(23)17(32-18)31-10-19(36,20(24,25)26)21(27,28)29/h1-8,36H,9-10H2,(H,30,31,32)
InChI Key CYSJNTQNMDWAJV-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. Breitenstein S, Roessig L, Sandner P, Lewis KS. (2017)
Novel sGC Stimulators and sGC Activators for the Treatment of Heart Failure.
Handb Exp Pharmacol, 243: 225-247. [PMID:27900610]
2. Flores-Costa R, Alcaraz-Quiles J, Titos E, López-Vicario C, Casulleras M, Duran-Güell M, Rius B, Diaz A, Hall K, Shea C et al.. (2018)
The soluble guanylate cyclase stimulator IW-1973 prevents inflammation and fibrosis in experimental non-alcoholic steatohepatitis.
Br J Pharmacol, 175 (6): 953-967. [PMID:29281143]
3. Tobin JV, Zimmer DP, Shea C, Germano P, Bernier SG, Liu G, Long K, Miyashiro J, Ranganath S, Jacobson S et al.. (2018)
Pharmacological Characterization of IW-1973, a Novel Soluble Guanylate Cyclase Stimulator with Extensive Tissue Distribution, Antihypertensive, Anti-Inflammatory, and Antifibrotic Effects in Preclinical Models of Disease.
J Pharmacol Exp Ther, 365 (3): 664-675. [PMID:29643251]
4. Udelson JE, Lewis GD, Shah SJ, Zile MR, Redfield MM, Burnett Jr J, Parker J, Seferovic JP, Wilson P, Mittleman RS et al.. (2020)
Effect of Praliciguat on Peak Rate of Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: The CAPACITY HFpEF Randomized Clinical Trial.
JAMA, 324 (15): 1522-1531. [PMID:33079154]