Sphingosine kinase inhibitors: a review of patent literature (2006-2015)

Expert Opinion on Therapeutic Patents

Volumn 26, Issue 12, 2016, Pages 1409-1416

  Lynch, Kevin R ^a   Thorpe, S Brandon ^b   Santos, Webster L ^c  

^a UNIVERSITY OF VIRGINIA   (United States)

^b SphynKx Therapeutics LLC   (United States)

^c VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY   (United States)

Author keywords

cancer therapeutics; kinase inhibitor; Sphingosine kinase; sphingosine kinase 1; sphingosine kinase 2; sphingosine 1 phosphate

Indexed keywords

3 (4 CHLOROPHENYL) N (4 PYRIDINYLMETHYL)ADAMANTANE 1 CARBOXAMIDE; BML 258; PHOSPHOTRANSFERASE INHIBITOR; SLR 080801; SPHINGOSINE KINASE INHIBITOR; UNCLASSIFIED DRUG; VPC 96091; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; PHOSPHOTRANSFERASE; SPHINGOSINE KINASE; SPHINGOSINE KINASE 2, HUMAN;

DRUG EFFICACY; DRUG INDICATION; DRUG INDUSTRY; DRUG RESEARCH; HUMAN; NONHUMAN; PATENT; REVIEW; SCIENTIFIC LITERATURE; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG DESIGN; GENETICS; METABOLISM; NEOPLASMS; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; NEOPLASMS; PATENTS AS TOPIC; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR);

EID: 84996529006     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1080/13543776.2016.1226282     Document Type: Review

References (52)

1. Mizugishi K, Yamashita T, Olivera A, et al. Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol. 2005;25:11113–11121.
2. Xiong Y, Hla T., S1P control of endothelial integrity. Curr Top Microbiol Immunol. 2014;378:85–105.
3. Pappu R, Schwab SR, Cornelissen I, et al. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007;316:295–298.
4. Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720):discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Dis. 2010;9:883–897.
5. Gault CR, Obeid LM. Still benched on its way to the bedside:sphingosine kinase 1 as an emerging target in cancer chemotherapy. Crit Rev Biochem Mol Biol. 2011;46:342–351.
6. French KJ, Schrecengost RS, Lee BD, et al. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. 2003;63:5962–5969.
7. Wang Z, Min X, Xiao S-H, et al. Molecular basis of sphingosine kinase 1 substrate recognition and catalysis. Structure. 2013;21:798–809.•• This paper describes the first crystal structure of SphK1 bound to Sph and early inhibitor, allowing future rational drug design.
8. Rex K, Jeffries S, Brown ML, et al. Sphingosine kinase activity is not required for tumor cell viability. PLoS One. 2013;8:e68328.• This paper demonstrates that SphK inhibitors do not play a major role in tumor cell viability.
9. Gustin DJ, Li Y, Brown ML, et al. Structure guided design of a series of sphingosine kinase (SphK) inhibitors. Bioorg Med Chem Lett. 2013;23:4608–4616.
10. Schnute ME, McReynolds MD, Kasten T, et al. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012;444:79–88.
11. Wang J, Knapp S, Pyne NJ, et al. Crystal structure of sphingosine kinase 1 with PF-543. ACS Med Chem Let. 2014;5:1329–1333.
12. Apogee Biotechnology. Sphingosine kinase inhibitors.US 7,220,764. 2007.
13. Apogee Biotechnology. Sphingosine kinase inhibitors and methods of their use.US 7,338,961. 2008.
14. Apogee Biotechnology. Sphingosine kinase inhibitors and methods of their use.US 8,063,248. 2011.
15. Apogee Biotechnology. Sphingosine kinase inhibitors and methods of their use.US 8,557,800. 2013.
16. French KJ, Zhuang Y, Maines LW, et al. Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharm Exp Therap. 2010;333:129–139.
17. Antoon JW, White MD, Meacham WD. Antiestrogenic effects of the novel sphingosine kinase-2 inhibitor ABC294640. Endocrinol. 2010;151:5124–5135.
18. Shi Y, Rehman H, Ramshesh VK, et al. Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion. J Hepat.2012;56:137–145.
19. Maines LW, Fitzpatrick LR, Green CL, et al. Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn’s disease. Inflammopharm. 2010;18:73–85.
20. Fitzpatrick LR, Green CL, Maines LW, et al. Experimental osteoarthritis in rats is attenuated by ABC294640, a selective inhibitor of sphingosine kinase-2. Pharmacology. 2011;87:135–143.
21. Apogee Biotechnology. Sphingosine kinase inhibitor prodrugs.US 8,685,936. 2014.
22. Apogee Biotechnology. Treatment of ischemia reperfusion injury.WO129954. 2010.
23. Merck Patent GmBH. Thiazol piperidine derivatives.US 8,436,186. 2013.
24. Merck Patent GmBH. Inhibitors of sphingosine kinase.US 8,907,098. 2014.
25. Merck Patent GmBH. Inhibitors of sphingosine kinase.US 9,062,015. 2015.
26. Paugh SW, Paugh BS, Rahmani M, et al. A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia. Blood. 2008;112:1382–1391.
27. Enzo Therapeutics. Novel SphK1 inhibitors, compositions and processes.US 8,314,151. 2013.
28. Enzo Therapeutics. Compositions and methods for inhibiting sphingosine kinases.US 8,686,066. 2014.
29. University of Virginia Patent Foundation. Compositions and methods for inhibiting sphingosine kinases.US 8,686,046. 2014.
30. Mathews TP, Kennedy AJ, Kharel Y, et al. Discovery, biological evaluation, and structure-activity relationship of amidine based sphingosine kinase inhibitors. J Med Chem. 2010;53:2766–2778.
31. University of Virginia Patent Foundation. Imidamide sphingosine kinase inhibitors.WO020116. 2011.
32. Kotthaus J, Steinmetzer T, Van De Locht A, et al. Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes). J Enz Inhib Med Chem. 2011;26:115–122.
33. Kharel Y, Mathews TP, Gellett AM, et al. Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating sphingosine 1-phosphate. Biochem J. 2011;440:345–353.
34. Kennedy AJ, Mathews TP, Kharel Y, et al. Development of amidine-based sphingosine kinase 1 nanomolar inhibitors and reduction of sphingosine 1-phosphate in human leukemia cells. J Med Chem. 2011;54:3524–3548.
35. University of Virginia Patent Foundation. Long chain base sphingosine kinase inhibitors.WO119946. 2013.
36. Kharel Y, Raje MR, Gao M, et al. Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphate. Biochem J. 2012;447:149–157.
37. Patwardhan NN, Morris EA, Kharel Y, et al. Structure-activity relationship studies and in vivo activity of guanidine based sphingosine kinase inhibitors:discovery of SphK 1 and 2 selective inhibitors. J Med Chem. 2012;58:1879–1899.• This publication reports potent and selective guanidine-based inhibitors with in vivo activity that track with S1P levels in blood.
38. Sensken SC, Bode C, Nagarajan M, et al. Redistribution of sphingosine 1-phosphate by sphingosine kinase 2 contributes to lymphopenia. J Immunol. 2010;184:4133–4142.
39. Kharel Y, Morris EA, Congdon MD, et al. Sphingosine kinase 2 inhibition and blood sphingosine 1-phosphate levels. J Pharm Exp Ther. 2015;355:23–31.•• This paper describes a relationship between elevated S1P levels upon SphK2 inhibition and decreased blood clearance of S1P.
40. Sun K, Zhang Y, D’Alessandro A, et al. Sphingosine 1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nature Comm. 2016;7:12086–12099.• This paper describes S1P as an intracellular hypoxia-responsive biolipid that promotes erythrocyte glycolysis and oxygen delivery.
41. Almac Discovery Ltd. Pharmaceutical compounds as inhibitors of sphingosine kinases.WO069852. 2012.
42. City University of New York & University of Strathclyde (UK). Selective inhibitors and allosteric activators of sphingosine kinases.WO118556. 2014.
43. Byun H-S, Pyne S, Macritchie N, et al. Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells. Med Chem Comm. 2013;4:1394–1399.
44. Kuroda I, Musman M, Ohtani I, et al. Pachastrissamine, a cytotoxic anhydrophytosphingosine from a marine sponge, Pachastrissa sp. J Nat Prod. 2002;65:1505–1506.
45. Baek DJ, MacRitchie N, Pyne NJ, et al. Synthesis of selective inhibitors of sphingosine kinase 1. Chem Comm. 2013;49:2136–2138.
46. Baek DJ, MacRitchie N, Anthony NG, et al. Structure-activity relationships and molecular modeling of sphingosine kinase inhibitors. J Med Chem. 2013;56:9310–9327.
47. Ajinomoto Corp. Sphingosine kinase inhibitor.WO157382. 2014.•• This patent describes SphK inhibitors bearing Pfizer’s 2-(hydroxymethyl)pyrrolidine head group.
48. University of South Australia. Benzene sulfonamide-based inhibitors of sphingosine kinases.WO007993. 2016.
49. Pitman MR, Powell JA, Coolen C, et al. A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties. Oncotarget. 2015;6:7065–7083.
50. Genzyme Corporation. Inhibitors of sphingosine kinase type 1.WO033701. 2010.
51. Xiang Y, Asmussen G, Booker M, et al. Discovery of novel sphingosine kinase 1 inhibitors. Bioorg Med Chem Lett. 2009;19:6119–6121.
52. Xiang Y, Hirth B, Kane JL, Jr., et al. Discovery of novel sphingosine kinase-1 inhibitors. Part 2. Bioorg Med Chem Lett. 2010;20:4550–4554.