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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2D Structure
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Physico-chemical Properties
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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
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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)
1. French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. (2010)
Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2.
J Pharmacol Exp Ther, 333 (1): 129-39. [PMID:20061445]
2. Kurd R, Ben-Chetrit E, Karameh H, Bar-Meir M. (2020)
Compassionate Use of Opaganib For Patients with Severe COVID-19.
medRxiv, Preprint. DOI: 10.1101/2020.06.20.20099010
3. Lewis CS, Voelkel-Johnson C, Smith CD. (2018)
Targeting Sphingosine Kinases for the Treatment of Cancer.
Adv Cancer Res, 140: 295-325. [PMID:30060814]