PCO371   Click here for help

GtoPdb Ligand ID: 12788

Synonyms: compound 16c [PMID: 32022560] | PCO-371
PDB Ligand
Compound class: Synthetic organic
Comment: PCO371 is an orally avaialble non-peptide parathyroid hormone receptor 1 (PTH1R) biased agonist [2-3] and was considered as a potential hypoparathyroidism treatment. This small molecule binds within the receptor intracellular cavity and stabilises the receptor-Gs interaction, thus biasing activation towards G protein signalling over β-arrestin recruitment [1].
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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

PCO371 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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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 11
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 145.86
Molecular weight 635.66
XLogP 1.75
No. Lipinski's rules broken 2

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 CC1=C(CCS(=O)(=O)N2CCC3(CC2)C(=O)NC(=N3)C4=CC=C(C=C4)OC(F)(F)F)C(=CC(=C1)N5C(=O)NC(=O)C5(C)C)C
Isomeric SMILES O=C1NC(=NC12CCN(S(=O)(CCC3=C(C=C(N4C(NC(C4(C)C)=O)=O)C=C3C)C)=O)CC2)C5=CC=C(C=C5)OC(F)(F)F
InChI InChI=1S/C29H32F3N5O6S/c1-17-15-20(37-26(40)34-24(38)27(37,3)4)16-18(2)22(17)9-14-44(41,42)36-12-10-28(11-13-36)25(39)33-23(35-28)19-5-7-21(8-6-19)43-29(30,31)32/h5-8,15-16H,9-14H2,1-4H3,(H,33,35,39)(H,34,38,40)
InChI Key LDZJFVOUPUFOHX-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/)
No information available.
Summary of Clinical Use Click here for help
Although PCO371 was advanced to clinical studies, a safety, tolerability, PK and PD study in volunteers with hypoparathyroidism, and a single ascending dose study in healthy subjects, were terminated.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04649216 Excretion Balance, PK and Metabolism of a Single Oral Dose of [14C]PCO371 Phase 1 Interventional Chugai Pharmaceutical
NCT04209179 A Clinical Study Investigating the Safety, Tolerability, PK and PD of PCO371 in Patients With Hypoparathyroidism Phase 1 Interventional Chugai Pharmaceutical
NCT02475616 A Single Ascending Dose Study of PCO371 in Healthy Volunteers Phase 1 Interventional Chugai Pharmaceutical