SPHK2 binds SPHK2 inhibitors

Stable Identifier
Reaction [binding]
Homo sapiens
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The bioactive sphingolipids ceramide, sphingosine and sphingosine-1-phosphate (S1P) are important signalling molecules whose balances can dictate cell fate. Ceramide and sphingosine enhance apoptosis and S1P promotes cell survival and proliferation. The sphingosine kinases (SPHKs) catalyse the production of S1P from sphingosine and are therefore central regulators of the sphingolipid rheostat. SPHKs are overexpressed in a variety of human cancers, making these enzymes potential molecular targets for cancer therapy.

Opaganib (ABC294640) selectively inhibits SPHK2 activity in vitro, attenuates S1P formation in intact cells and, in tissue culture, it suppresses the proliferation of a broad panel of tumor cell lines (Gao et al. 2012, French et al. 2010). Both isoforms of SPHK have been shown to regulate the replication or pathogenicity of many viruses (Wolf et al. 2019).

Other investigational SPHK2 inhibitors include ROMe (Lim et al. 2011), MP-A08 (Pitman et al. 2015) and SLM6071469 (Compound 10) (Sibley et al. 2020).
Literature References
PubMed ID Title Journal Year
25788259 A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties

Ebert, LM, Pitson, SM, Coolen, C, Powell, JA, Finnie, JW, Don, AS, Bonder, CS, Moretti, PA, Zebol, JR, Pitman, MR, Pham, DH, Gliddon, BL

Oncotarget 2015
21620961 (R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect on sphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells

Lim, KG, Bittman, R, Pyne, NJ, Sun, C, Pyne, S

Cell. Signal. 2011
31895563 Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity

Kharel, Y, Sibley, CD, Bevan, DR, Morris, EA, Brown, AM, Lynch, KR, Santos, WL, Huang, T

J. Med. Chem. 2020
31783527 Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections

Studstill, CJ, Hahm, B, Wolf, JJ

Viruses 2019
22970244 Characterization of isoenzyme-selective inhibitors of human sphingosine kinases

Smith, RA, Smith, CD, Peterson, YK, Gao, P

PLoS ONE 2012
20061445 Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2

Zhuang, Y, Wang, W, French, KJ, Green, CL, Smith, CD, Beljanski, V, Maines, LW, Upson, JJ, Keller, SN, Gao, P

J. Pharmacol. Exp. Ther. 2010
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