Home Immunology & Inflammation SPHK inhibitor Opaganib (ABC294640)

Opaganib (ABC294640)

Catalog No.S7174

For research use only.

Opaganib (ABC294640) is an orally bioavailable and selective sphingosine kinase-2 (SphK2) inhibitor with IC50 of approximately 60 μM. Phase 1/2.

Opaganib (ABC294640) Chemical Structure

CAS No. 915385-81-8

Selleck's Opaganib (ABC294640) has been cited by 13 publications

Purity & Quality Control

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Biological Activity

Description Opaganib (ABC294640) is an orally bioavailable and selective sphingosine kinase-2 (SphK2) inhibitor with IC50 of approximately 60 μM. Phase 1/2.
Targets
SphK2 [1]
(Cell-free assay)
60 μM
In vitro

ABC294640 markedly alters the ratio of ceramide/S1P consistent with inhibition of SK activity in MDA-MB-231 cells. ABC294640 inhibits tumor cell proliferation with IC50 values ranging from approximately 6 to 48 μM, and impairs tumor cell migration concomitant with loss of microfilaments. [1] ABC294640 induces nonapoptotic cell death, morphological changes in lysosomes, formation of autophagosomes, and increases in acidic vesicles in A-498, PC-3, and MDA-MB-231 cells. [2] In both MCF-7 and ER-transfected HEK293 cells, ABC294640 decreases E2-stimulated ERE-luciferase activity. [3]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 MnLVSpVv[3Srb36gZZN{[Xl? MX3Jcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KFOyaFuyJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiYYPz[ZN{\WRiYYOgdoFlcW:uYXLlcIVlKHC{b3T1Z5R{KHW|aX7nJFExKHWPIIPwbIlv\2:|aX7lJIFv\CBzMDD1UUBo[W2vYWuzNnBeSVSSIHL5JIxqeXWrZDDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCNaU25MljPxE1? NH3VSXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0N|A4PCd-MkW2OFMxPzR:L3G+
Sf9 NFnwUFZHfW6ldHnvckBie3OjeR?= NFHpeoQzKGi{cx?= Mn3qTY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDoeY1idiCodXzsMYxmdme2aDDOMZRmem2rbnHsJGhqey22YXfn[YQhW0t{IHX4dJJme3OnZDDpckBj[WO3bH;2bZJ2eyCrbn\lZ5Rm\CCVZkmgbY5{\WO2IHPlcIx{KHW|aX7nJG5DTC2VcHigZZMhe3Wkc4TyZZRmKG2nYYP1doVlKGGodHXyJFIhcHK|IHL5JIZtfW:{ZYPj[Y5k\SCkYYPl[EBJWEyFIHHuZYx6e2m|LDDLbV06NjkQvF2= MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODh6OUO1Nkc,OzB6OEmzOVI9N2F-
Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot c-Myc ; pRb / Rb ; H3K9ac / p21 ; p-STAT3 / STAT3 27517489 26956050
Growth inhibition assay Cell proliferation 25122609
In vivo In mice bearing mammary adenocarcinoma xenografts, ABC294640 (100 mg/kg, p.o.) significantly reduce tumor growth, associated with depletion of S1P levels. [1] In severe combined immunodeficient mice bearing A-498 xenografts, ABC294640 delays tumor growth and elevates autophagy markers. [2] ABC294640 protects against liver transplantation-induced inflammation and cross-talk between innate and adaptive immunities, major events precipitating and exacerbating graft injury, and improves liver function and survival. [4]

Protocol (from reference)

Kinase Assay:[1]
  • Sphingosine Kinase Assays:

    The IC50 values for ABC294640 and DMS are determined by a newly developed HPLC-based SK activity assay. In brief, the test compounds are incubated with recombinant SK1 or SK2 and NBD-Sph in the isozyme-selective assay buffers detailed below with 1 mg/ml fatty acid-free bovine serum albumin, 100 μM ATP, and 400 μM MgCl2. The product, i.e., NBD-S1P, is separated from NBD-Sph by HPLC as follows: Waters 2795 HPLC system with a Waters 2495 fluorescence detector, C8 Chromolith RP-8e column (100 × 4.6 mm), 1 ml/min mobile phase (acetonitrile/20 mM sodium phosphate buffer, pH2.5, at 45:55). Fluorescence is monitored with excitation at 465 nm and emission at 531 nm. The ratio of NBD-S1P/(NBD-Sph + NBD-S1P) is used as a measure of SK activity. SK-isozyme selective assay buffers each contained 20 mM Tris, pH7.4, 5 mM EDTA, 5 mM EGTA, 3 mM β-mercaptoethanol, 5% glycerol, 1× protease inhibitors and 1× phosphatase inhibitors. For the SK1 assay buffer, 0.25% (final) Triton X-100 is added; and for the SK2 buffer, 1 M (final) KCl is added. Assays are run for 2 h at room temperature, and then a 1.5 volume of methanol is added to terminate the kinase reaction. After 10 min, the samples are centrifuged at 20,000g to pellet the precipitated protein, and the supernatants are analyzed by HPLC. In experiments to determine the Ki for inhibition of SK2 by ABC294640, the ADP Quest assay system is used to measure kinase activity in the presence of varying concentrations of sphingosine and ABC294640. To determine the effects of ABC294640 on cellular SK activity, near-confluent MDA-MB-231 cells are serum-starved overnight, and then treated with varying concentrations of ABC294640. The cells are then incubated with [3H]sphingosine at a final concentration of 1 μM. The cells take up the exogenous sphingosine, which is converted to S1P via SK activity, and [3H]S1P is separated from [3H]sphingosine by extraction and quantified by scintillation counting.
Cell Research:[1]
  • Cell lines: 1025LU, Hep-G2, A-498, MCF-7, Caco-2, MDA-MB-231, HT-29, Panc-1, DU145, T24, and SK-OV-3 cell lines
  • Concentrations: ~50 μM
  • Incubation Time: 72 h
  • Method: To determine the effects of the test compounds on proliferation, cells are plated into 96-well microtiter plates and allowed to attach for 24 h. Varying concentrations of ABC294640 are added to individual wells and the cells are incubated for an additional 72 h. At the end of this period, the number of viable cells is determined by use of the sulforhodamine-binding assay. The percentage of cells killed is calculated as the percentage decrease in sulforhodamine-binding compared with control cultures. Regression analyses of inhibition curves are performed by use of GraphPad Prism.
Animal Research:[1]
  • Animal Models: Female BALB/c mice bearing JC tumors
  • Dosages: ~100 mg/kg
  • Administration: p.o.

Solubility (25°C)

In vitro

 DMSO 76 mg/mL warmed
(199.52 mM)
Water Insoluble
Ethanol ''28 mg/mL

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

 5mg/mL

Chemical Information

Molecular Weight 380.91
Formula

C23H25ClN2O
CAS No. 915385-81-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1C2CC3(CC1CC(C2)(C3)C(=O)NCC4=CC=NC=C4)C5=CC=C(C=C5)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02939807 Withdrawn Drug: ABC294640 Carcinoma Hepatocellular Medical University of South Carolina|National Cancer Institute (NCI)|Apogee Biotechnology Corporation September 30 2019 Phase 2
NCT03377179 Recruiting Drug: ABC294640|Drug: Hydroxychloroquine Sulfate 200 MG Cholangiocarcinoma|Cholangiocarcinoma Non-resectable|Cholangiocarcinoma Perihilar|Cholangiocarcinoma Extrahepatic|Cholangiocarcinoma Intrahepatic RedHill Biopharma Limited March 7 2018 Phase 2
NCT02757326 Terminated Drug: Opaganib Multiple Myeloma RedHill Biopharma Limited|Apogee Biotechnology Corporation|Duke University|National Cancer Institute (NCI) December 13 2016 Phase 1|Phase 2
NCT02229981 Withdrawn Drug: ABC294640 Diffuse Large B Cell Lymphoma|Kaposi Sarcoma RedHill Biopharma Limited|Louisiana State University Health Sciences Center in New Orleans|Apogee Biotechnology Corporation July 2014 Phase 1|Phase 2
NCT01488513 Completed Drug: sphingosine kinase-2 inhibitor ABC294640 Pancreatic Cancer|Unspecified Adult Solid Tumor Protocol Specific RedHill Biopharma Limited|Apogee Biotechnology Corporation|Medical University of South Carolina|FDA Office of Orphan Products Development|National Cancer Institute (NCI) August 2011 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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