sitokiren   Click here for help

GtoPdb Ligand ID: 12196

Synonyms: compound 18 [PMID: 35939295] | SPH-3127 | SPH3127
Compound class: Synthetic organic
Comment: SPH3127 is an orally active direct renin inhibitor [1]. It induces a more potent antihypertensive effect in in vivo models than the approved renin inhibitor aliskiren. The chemical structure for SPH3127 matches that for the INN sitokiren (proposed INN list 130, Feb. 2024).
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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 9
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 110.61
Molecular weight 444.25
XLogP 1.75
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 COC(=O)NCCCn1nc(c2c1nc(C)cc2)[C@H](N(C(=O)[C@H]1CNCCO1)C1CC1)C
Isomeric SMILES COC(=O)NCCCn1nc([C@@H](C)N(C2CC2)C(=O)[C@H]2CNCCO2)c2ccc(C)nc12
InChI InChI=1S/C22H32N6O4/c1-14-5-8-17-19(26-27(20(17)25-14)11-4-9-24-22(30)31-3)15(2)28(16-6-7-16)21(29)18-13-23-10-12-32-18/h5,8,15-16,18,23H,4,6-7,9-13H2,1-3H3,(H,24,30)/t15-,18-/m1/s1
InChI Key GRTDDIZIUSADLD-CRAIPNDOSA-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
SPH3127 has been advanced to phase 3 clinical evaluation to determine efficacy as an anti-hypertensive agent.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05359068 Study to Evaluate the Efficacy and Safety of SPH3127 In Patients With Mild-moderate Essential Hypertension Phase 3 Interventional Shanghai Pharmaceuticals Holding Co., Ltd
NCT03756103 Safety and Efficacy of SPH3127 on Treating Mild-moderate Essential Hypertension Patients Phase 2 Interventional Shanghai Pharmaceuticals Holding Co., Ltd
NCT03255993 The Tolerability and Pharmacokinetics of Multiple Doses of SPH3127 in Chinese Healthy People Phase 1 Interventional Shanghai Pharmaceuticals Holding Co., Ltd 2
NCT03128138 Single Ascending Dose Study of Safety and Tolerability of SPH3127 Tablet in Chinese Healthy Volunteers Phase 1 Interventional Shanghai Pharmaceuticals Holding Co., Ltd 2