opaganib   Click here for help

GtoPdb Ligand ID: 6624

Synonyms: ABC 294640 | ABC-294640 | Yeliva®
Compound class: Synthetic organic
Comment: Opaganib (ABC294640) is an orally bioavailable sphingosine kinase 2-selective inhibitor that is being investigated for clinical antiproliferative efficacy in various cancers [3]. The sphingosine kinases (SK1 and SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. Opaganib is being developed by RedHill Bio. In 2017 the FDA granted this compound orphan designation for the treatment of cholangiocarcinoma.

SARS-CoV-2 and COVID-19: A medRxiv preprint descibes the compassionate use of opaganib in a small cohort of patients with severe COVID-19 [2], predicated upon the drug's anti-inflammatory and anti-viral properties. The analysis indicated trends in favour of clinical efficacy which led to extended investigation in a Phase 2 randomised placebo-controlled trial.
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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 3
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 41.99
Molecular weight 380.17
XLogP 5.03
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 Clc1ccc(cc1)C12CC3CC(C1)CC(C2)(C3)C(=O)NCc1ccncc1
Isomeric SMILES Clc1ccc(cc1)C12CC3CC(C1)CC(C2)(C3)C(=O)NCc1ccncc1
InChI InChI=1S/C23H25ClN2O/c24-20-3-1-19(2-4-20)22-10-17-9-18(11-22)13-23(12-17,15-22)21(27)26-14-16-5-7-25-8-6-16/h1-8,17-18H,9-15H2,(H,26,27)
InChI Key CAOTVXGYTWCKQE-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
ABC294640 has advanced to clinical evaluation in patients with advanced cholangiocarcinoma, advanced hepatocellular carcinoma and refractory/relapsed multiple myeloma (to view ClinicalTrials.gov's list of ABC294640 trials click here).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04414618 A Study of Opaganib in Coronavirus Disease 2019 Pneumonia Phase 2 Interventional RedHill Biopharma Limited
NCT03377179 A Study of ABC294640 (Yeliva ®) Alone and in Combination With Hydroxychloroquine Sulfate in Treatment of Patients With Advanced Cholangiocarcinoma Phase 2 Interventional RedHill Biopharma Limited 2
NCT04435106 Compassionate Use of Opaganib in Patients With Coronavirus Disease 2019 (COVID-19) Observational Shaare Zedek Medical Center Results analysis indicated trends in favour of clinical efficacy, along with favourable safety, which led to extended investigation in a Phase 2 randomised placebo-controlled trial in patients with COVID-19 pneumonia. 2