ABC294640
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205806

CAS#: 915385-81-8 (free base)

Description: ABC294640, also known as Opaganib, is an orally available, aryladamantane compound and selective inhibitor of sphingosine kinase-2 (SK2) with potential antineoplastic activity. Upon administration, ABC294640 competitively binds to and inhibits SK2, thereby preventing the phosphorylation of the pro-apoptotic amino alcohol sphingosine to sphingosine 1-phosphate (S1P), the lipid mediator that is pro-survival and critical for immunomodulation. This may eventually lead to the induction of apoptosis and may result in an inhibition of cell proliferation in cancer cells overexpressing SK2.

Chemical Structure

img
ABC294640
CAS# 915385-81-8 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205806
Name: ABC294640
CAS#: 915385-81-8 (free base)
Chemical Formula: C23H25ClN2O
Exact Mass: 380.17
Molecular Weight: 380.910
Elemental Analysis:

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2450 Ready to ship
Bulk inquiry

Related CAS #: 1185157-59-8 (HCl)   915385-81-8 (free base)    

Synonym: ABC-294640; ABC294640; ABC 294640; Opaganib

IUPAC/Chemical Name: (1s,3r,5R,7S)-3-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)adamantane-1-carboxamide

InChi Key: CAOTVXGYTWCKQE-BRNYJPRKSA-N

InChi Code: 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)/t17-,18+,22+,23-

SMILES Code: O=C([C@@]12C[C@]3(C4=CC=C(Cl)C=C4)C[C@@](C2)([H])C[C@](C3)([H])C1)NCC5=CC=NC=C5

Appearance: White solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: ABC294640 selectively inhibits SK2 activity in vitro, acting as a competitive inhibitor with respect to sphingosine with a K(i) of 9.8 muM, and attenuates S1P formation in intact cells. In tissue culture, ABC294640 suppresses the proliferation of a broad panel of tumor cell lines, and inhibits tumor cell migration concomitant with loss of microfilaments. In vivo, ABC294640 has excellent oral bioavailability, and demonstrates a plasma clearance half-time of 4.5 h in mice. Oral administration of ABC294640 to mice bearing mammary adenocarcinoma xenografts results in dose-dependent antitumor activity associated with depletion of S1P levels in the tumors and progressive tumor cell apoptosis. Therefore, this newly developed SK2 inhibitor provides an orally available drug candidate for the treatment of cancer and other diseases.   (source: J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. Epub 2010 Jan 8.)      

Biological target: Opaganib (ABC294640) is a selective, competitive sphingosine kinase 2 (SK2) inhibitor with Ki of 9.8 μM.
In vitro activity: An aryladamantane compound, termed ABC294640 [3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide], was identified to selectively inhibit SK2 activity in vitro, acting as a competitive inhibitor with respect to sphingosine with a K(i) of 9.8 muM, and attenuates S1P formation in intact cells. In tissue culture, ABC294640 suppresses the proliferation of a broad panel of tumor cell lines, and inhibits tumor cell migration concomitant with loss of microfilaments. Using recombinant human SK1 and SK2, ABC294640 demonstrated dose-dependent inhibition of SK2 with an IC50 of approximately 60 μM without affecting the activity of SK1 at concentrations up to at least 100 μM (Fig. 2A). Additional studies demonstrated that ABC294640 acts as a competitive inhibitor with respect to sphingosine, making the IC50 strongly affected by the concentration of sphingosine used in the assay. Kinetic analyses of varying concentrations of ABC294640 in the presence of 2.5 to 25 μM sphingosine indicated a Ki of 9.8 ± 1.4 μM for the inhibition of SK2 (Fig. 2B). It was also important to determine the ability of ABC294640 to inhibit endogenous SK activity in an intact cell model. MDA-MB-231 cells were incubated with [3H]sphingosine at a final concentration of 1 μM to test this. In this assay, ABC294640 decreased [3H]S1P formation in a dose-dependent fashion with an IC50 value of 26 μM. The effects of ABC294640 on the proliferation of human tumor cell lines representing major tumor types were determined by use of the sulforhodamine B assay for quantifying cell number. As indicated in Table 2, ABC294640 inhibited tumor cell proliferation with IC50 values ranging from approximately 6 to 48 μM with Hep-G2 and HT-29 cells being the most and least sensitive, respectively. It is notable that the IC50 for inhibition of the proliferation of MDA-MB-231 cells closely matches the IC50 for suppression of SK activity in this cell line, i.e., 29 and 26 μM, respectively, supporting the hypotheses that the antiproliferative effects of ABC294640 are mediated by inhibition of SK activity, and that SK2, in particular, is important for cell proliferation. Reference: J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20061445/
In vivo activity: The antitumor activity of ABC294640 was tested in a syngeneic tumor model that uses the mouse JC mammary adenocarcimona cell line growing subcutaneously in immunocompetent BALB/c mice. Because of the excellent oral absorption, it was determined the ability of orally delivered ABC294640 to reduce tumor growth in vivo. The SK inhibitor was administered to fasted mice on odd days at doses ranging from 3.5 to 100 mg/kg. Body weights and tumor volumes were monitored daily. As demonstrated in Fig. 7, ABC294640 caused dose-dependent reductions in the growth of the mammary adenocarcinoma xenografts. Body weights in each treatment group remained unchanged from vehicle-treated mice during the course of the study (data not shown). Comparison with the potencies in the tumor studies with the toxicity data described above reveals that ABC294640·HCl has a therapeutic index of greater than 7 (250 mg/kg nontoxic dose / 35 mg/kg antitumor activity). Thus, this SK2 inhibitor has an excellent therapeutic index. Reference: J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20061445/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 76.0 199.52
Ethanol 28.0 73.51

Preparing Stock Solutions

The following data is based on the product molecular weight 380.91 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. doi: 10.1124/jpet.109.163444. Epub 2010 Jan 8. PMID: 20061445; PMCID: PMC2846016. 2. Beljanski V, Knaak C, Zhuang Y, Smith CD. Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. Invest New Drugs. 2011 Dec;29(6):1132-42. doi: 10.1007/s10637-010-9452-0. Epub 2010 May 18. PMID: 20473784; PMCID: PMC3089696.
In vivo protocol: 1. French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. doi: 10.1124/jpet.109.163444. Epub 2010 Jan 8. PMID: 20061445; PMCID: PMC2846016. 2. Beljanski V, Knaak C, Zhuang Y, Smith CD. Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. Invest New Drugs. 2011 Dec;29(6):1132-42. doi: 10.1007/s10637-010-9452-0. Epub 2010 May 18. PMID: 20473784; PMCID: PMC3089696.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Zhang F, Hu W, Qu L, Cang C. Sphingosine kinase 2 inhibitor ABC294640 suppresses neuronal excitability and inhibits multiple endogenously and exogenously expressed voltage-gated ion channels in cultured cells. Channels (Austin). 2020 Dec;14(1):216-230. doi: 10.1080/19336950.2020.1788364. PMID: 32615066; PMCID: PMC7515484.


2: Xu L, Jin L, Yang B, Wang L, Xia Z, Zhang Q, Xu J. The sphingosine kinase 2 inhibitor ABC294640 inhibits cervical carcinoma cell growth. Oncotarget. 2017 Dec 19;9(2):2384-2394. doi: 10.18632/oncotarget.23415. PMID: 29416779; PMCID: PMC5788647.


3: Dai L, Chen J, Lin Z, Wang Z, Mu S, Qin Z. Targeting Sphingosine Kinase by ABC294640 against Diffuse Intrinsic Pontine Glioma (DIPG). J Cancer. 2020 May 22;11(16):4683-4691. doi: 10.7150/jca.46269. PMID: 32626514; PMCID: PMC7330698.


4: Zhou J, Chen J, Yu H. Targeting sphingosine kinase 2 by ABC294640 inhibits human skin squamous cell carcinoma cell growth. Biochem Biophys Res Commun. 2018 Mar 4;497(2):535-542. doi: 10.1016/j.bbrc.2018.02.075. Epub 2018 Feb 8. PMID: 29428730.


5: Song K, Dai L, Long X, Cui X, Liu Y, Di W. Sphingosine kinase 2 inhibitor ABC294640 displays anti-epithelial ovarian cancer activities in vitro and in vivo. Onco Targets Ther. 2019 Jun 6;12:4437-4449. doi: 10.2147/OTT.S208519. PMID: 31239712; PMCID: PMC6560197.


6: Dai L, Bai A, Smith CD, Rodriguez PC, Yu F, Qin Z. ABC294640, A Novel Sphingosine Kinase 2 Inhibitor, Induces Oncogenic Virus-Infected Cell Autophagic Death and Represses Tumor Growth. Mol Cancer Ther. 2017 Dec;16(12):2724-2734. doi: 10.1158/1535-7163.MCT-17-0485. Epub 2017 Sep 22. PMID: 28939554; PMCID: PMC5716930.


7: Yang J, Yang C, Zhang S, Mei Z, Shi M, Sun S, Shi L, Wang Z, Wang Y, Li Z, Xie C. ABC294640, a sphingosine kinase 2 inhibitor, enhances the antitumor effects of TRAIL in non-small cell lung cancer. Cancer Biol Ther. 2015;16(8):1194-204. doi: 10.1080/15384047.2015.1056944. PMID: 26054751; PMCID: PMC4623419.


8: French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010 Apr;333(1):129-39. doi: 10.1124/jpet.109.163444. Epub 2010 Jan 8. PMID: 20061445; PMCID: PMC2846016.


9: Xun C, Chen MB, Qi L, Tie-Ning Z, Peng X, Ning L, Zhi-Xiao C, Li-Wei W. Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo. J Exp Clin Cancer Res. 2015 Sep 4;34(1):94. doi: 10.1186/s13046-015-0205-y. PMID: 26337959; PMCID: PMC4559903.


10: Britten CD, Garrett-Mayer E, Chin SH, Shirai K, Ogretmen B, Bentz TA, Brisendine A, Anderton K, Cusack SL, Maines LW, Zhuang Y, Smith CD, Thomas MB. A Phase I Study of ABC294640, a First-in-Class Sphingosine Kinase-2 Inhibitor, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017 Aug 15;23(16):4642-4650. doi: 10.1158/1078-0432.CCR-16-2363. Epub 2017 Apr 18. PMID: 28420720; PMCID: PMC5559328.


11: Venant H, Rahmaniyan M, Jones EE, Lu P, Lilly MB, Garrett-Mayer E, Drake RR, Kraveka JM, Smith CD, Voelkel-Johnson C. The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo. Mol Cancer Ther. 2015 Dec;14(12):2744-52. doi: 10.1158/1535-7163.MCT-15-0279. Epub 2015 Oct 22. PMID: 26494858; PMCID: PMC4674301.


12: White MD, Chan L, Antoon JW, Beckman BS. Targeting ovarian cancer and chemoresistance through selective inhibition of sphingosine kinase-2 with ABC294640. Anticancer Res. 2013 Sep;33(9):3573-9. PMID: 24023282.


13: Guan S, Liu YY, Yan T, Zhou J. Inhibition of ceramide glucosylation sensitizes lung cancer cells to ABC294640, a first-in-class small molecule SphK2 inhibitor. Biochem Biophys Res Commun. 2016 Aug 5;476(4):230-236. doi: 10.1016/j.bbrc.2016.05.102. Epub 2016 May 21. PMID: 27221045.


14: Schrecengost RS, Keller SN, Schiewer MJ, Knudsen KE, Smith CD. Downregulation of Critical Oncogenes by the Selective SK2 Inhibitor ABC294640 Hinders Prostate Cancer Progression. Mol Cancer Res. 2015 Dec;13(12):1591-601. doi: 10.1158/1541-7786.MCR-14-0626. Epub 2015 Aug 13. PMID: 26271487; PMCID: PMC4685021.


15: Fitzpatrick LR, Green C, Maines LW, Smith CD. Experimental osteoarthritis in rats is attenuated by ABC294640, a selective inhibitor of sphingosine kinase-2. Pharmacology. 2011;87(3-4):135-43. doi: 10.1159/000323911. Epub 2011 Feb 22. PMID: 21346391.


16: Beljanski V, Lewis CS, Smith CD. Antitumor activity of sphingosine kinase 2 inhibitor ABC294640 and sorafenib in hepatocellular carcinoma xenografts. Cancer Biol Ther. 2011 Mar 1;11(5):524-34. doi: 10.4161/cbt.11.5.14677. Epub 2011 Mar 1. PMID: 21258214; PMCID: PMC3087901.


17: Grbčić P, Eichmann TO, Kraljević Pavelić S, Sedić M. The Sphingosine Kinase 2 Inhibitor ABC294640 Restores the Sensitivity of BRAFV600E Mutant Colon Cancer Cells to Vemurafenib by Reducing AKT-Mediated Expression of Nucleophosmin and Translationally-Controlled Tumour Protein. Int J Mol Sci. 2021 Oct 5;22(19):10767. doi: 10.3390/ijms221910767. PMID: 34639107; PMCID: PMC8509245.


18: Ding X, Chaiteerakij R, Moser CD, Shaleh H, Boakye J, Chen G, Ndzengue A, Li Y, Zhou Y, Huang S, Sinicrope FA, Zou X, Thomas MB, Smith CD, Roberts LR. Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells. Oncotarget. 2016 Apr 12;7(15):20080-92. doi: 10.18632/oncotarget.7914. PMID: 26956050; PMCID: PMC4991440.


19: Hasanifard L, Samadi N, Rashtchizadeh N, Dastmalchi S, Karimi P. Sphingosine kinase-2 Inhibitor ABC294640 Enhances Doxorubicin-Induced Apoptosis of NSCLC Cells via Altering Survivin Expression. Drug Res (Stuttg). 2018 Jan;68(1):45-53. doi: 10.1055/s-0043-117181. Epub 2017 Sep 26. Erratum in: Drug Res (Stuttg). 2018 Jan;68(1):e1. PMID: 28950390.


20: Sundaramoorthy P, Gasparetto C, Kang Y. The combination of a sphingosine kinase 2 inhibitor (ABC294640) and a Bcl-2 inhibitor (ABT-199) displays synergistic anti-myeloma effects in myeloma cells without a t(11;14) translocation. Cancer Med. 2018 Jul;7(7):3257-3268. doi: 10.1002/cam4.1543. Epub 2018 May 15. PMID: 29761903; PMCID: PMC6051232.

1. Tran HB, Barnawi J, Ween M, Hamon R, Roscioli E, Hodge G, Reynolds PN, Pitson SM, Davies LT, Haberberger R, Hodge S. Cigarette smoke inhibits efferocytosis via deregulation of sphingosine kinase signaling: reversal with exogenous S1P and the S1P analogue FTY720. J Leukoc Biol. 2016 Jul;100(1):195-202. doi: 10.1189/jlb.3A1015-471R. Epub 2016 Jan 20. PMID: 26792820.

2. Al-Shujairi WH, Clarke JN, Davies LT, Pitman MR, Calvert JK, Aloia AL, Pitson SM, Carr JM. In vitro and in vivo roles of sphingosine kinase 2 during dengue virus infection. J Gen Virol. 2019 Apr;100(4):629-641. doi: 10.1099/jgv.0.001245. Epub 2019 Mar 14. PMID: 30869582.

3. Wallington-Beddoe CT, Bennett MK, Vandyke K, Davies L, Zebol JR, Moretti PAB, Pitman MR, Hewett DR, Zannettino ACW, Pitson SM. Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress. Oncotarget. 2017 Jul 4;8(27):43602-43616. doi: 10.18632/oncotarget.17115. PMID: 28467788; PMCID: PMC5546428

4. Gardner NM, Riley RT, Showker JL, Voss KA, Sachs AJ, Maddox JR, Gelineau-van Waes JB. Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts. Toxicol Appl Pharmacol. 2016 May 1;298:56-65. doi: 10.1016/j.taap.2016.02.018. Epub 2016 Feb 22. PMID: 26905748.

5. Xia C, Seo YJ, Studstill CJ, Vijayan M, Wolf JJ, Hahm B. Transient inhibition of sphingosine kinases confers protection to influenza A virus infected mice. Antiviral Res. 2018 Oct;158:171-177. doi: 10.1016/j.antiviral.2018.08.010. Epub 2018 Aug 17. PMID: 30125617; PMCID: PMC6190705.

6. Hasanifard L, Samadi N, Rashtchizadeh N, Dastmalchi S, Karimi P. Sphingosine kinase-2 Inhibitor ABC294640 Enhances Doxorubicin-Induced Apoptosis of NSCLC Cells via Altering Survivin Expression. Drug Res (Stuttg). 2018 Jan;68(1):45-53. doi: 10.1055/s-0043-117181. Epub 2017 Sep 26. Erratum in: Drug Res (Stuttg). 2018 Jan;68(1):e1. PMID: 28950390.

7. Bandara G, Muñoz-Cano R, Tobío A, Yin Y, Komarow HD, Desai A, Metcalfe DD, Olivera A. Targeting Sphingosine Kinase Isoforms Effectively Reduces Growth and Survival of Neoplastic Mast Cells With D816V-KIT. Front Immunol. 2018 Mar 28;9:631. doi: 10.3389/fimmu.2018.00631. PMID: 29643855; PMCID: PMC5883065.

8. Studstill CJ, Pritzl CJ, Seo YJ, Kim DY, Xia C, Wolf JJ, Nistala R, Vijayan M, Cho YB, Kang KW, Lee SM, Hahm B. Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence. J Clin Invest. 2020 Dec 1;130(12):6523-6538. doi: 10.1172/JCI125297. PMID: 32897877; PMCID: PMC7685747.

9.