PF-00489791   Click here for help

GtoPdb Ligand ID: 8377

Synonyms: PF-489,791 | PF-489791
Compound class: Synthetic organic
Comment: PF-00489791 is a long-acting, selective and competitive inhibitor of phosphodiesterase 5 (gene symbol PDE5A) inhibitor which is reported to reduce systemic blood pressure in patients with hypertension [2].
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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
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 CDK toolkit. 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 11
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 152.61
Molecular weight 476.2
XLogP 2.11
No. Lipinski's rules broken 1
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.

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Canonical SMILES CCOCCn1nc(c2c1c(Nc1nccc(c1)C)nc(n2)N(CC)C)C(=O)NS(=O)(=O)C
Isomeric SMILES CCOCCn1nc(c2c1c(Nc1nccc(c1)C)nc(n2)N(CC)C)C(=O)NS(=O)(=O)C
InChI InChI=1S/C20H28N8O4S/c1-6-27(4)20-23-15-16(19(29)26-33(5,30)31)25-28(10-11-32-7-2)17(15)18(24-20)22-14-12-13(3)8-9-21-14/h8-9,12H,6-7,10-11H2,1-5H3,(H,26,29)(H,21,22,23,24)
InChI Key ZUHZNKJIJDAJFD-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
PF-00489791 has been evaluated in Phase 2 clinical trials as a potential treatment for hypertension, diabetic nephropathies and Raynaud's disease (a peripheral vascular disease).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
PDE5 in arterial and venous vascular smooth muscle (VSM) cells is responsible for metabolising cyclic GMP (cGMP) to inactive 5'-GMP, in the control of arterial vascular resistance. Inhibition of PDE5 effectively increases cGMP levels, which results in reduced intracellular calcium in VSM cells and leads to arterial and venous vasorelaxation and a reduction in systemic blood pressure. The hypothesis underlying the use of PDE5 inhibition in diabetic nephropathy, is that reducing blood pressure in the kidney will improve renal function thereby increasing the removal of the toxins responsible for kidney damage. PDE5 inhibition may also act to restore the integrity of the nitrous oxide (NO) signalling pathway, which may be impaired in chronic kidney disease.