ACS Medicinal Chemistry Letters
Page 6 of 7
2. Yang, L.; Xie, G.; Fan, Q.; Xie, J. Activation of the hedgehogꢀ
signaling pathway in human cancer and the clinical implications.
Oncogene 2010, 29, 469ꢀ481.
3. Peukert, S. and MillerꢀMoslin, K. Smallꢀmolecule inhibitors of the
hedgehog signaling pathway as cancer therapeutics. ChemMedChem
2010, 5, 500ꢀ512.
4. Corcoran, R.B.; Scott, M.P. Oxysterols stimulate sonic hedgehog
signal transduction and proliferation of medulloblastoma cells. Proc.
Natl. Acad. Sci. 2006, 103, 8408ꢀ8413.
5. Dwyer, J.R.; Sever, N.; Carlson, M.; Nelson, S.F.; Beachy, P.A.;
Parhami, F. Oxysterols and novel activators of the hedgehog signaling
pathway in pluripotent mesenchymal cells. J. Bio. Chem. 2007, 282,
8959ꢀ8968.
compound squalamine: 6βꢀhydroxyꢀ3ꢀaminosterols synthesized from
1
2
3
4
5
6
7
8
hyodeoxycholic acid. Steroids, 1996, 61, 565ꢀ571.
23. Bharucha, K.R.; Buckley, G.C.; Cross, C.K.; Rubin, L.J.; Ziegler,
P. The conversion of hyodesoxycholic acid to progesterone. Can. J.
Chem., 1956, 34, 982ꢀ990.
24. Shen, Y.; Wen,J; A new route for synthesizing cholesterol analogs
with fluorocarbon side chains and their liquidꢀcrystalline aliphatic
esters. J. Fluor. Chem. 2002, 113, 13ꢀ15.
25. Hirano, Y.; Eguchi, T; Ishiguor, M.; Ikekawa, N. 23,25ꢀ
Dihydroxycholesterols. Chem. Pharm. Bull. 1983, 31, 394ꢀ400.
26. Honda, T.; Katoh, M.; Yamane, SꢀI. Stereoselective synthesis of
petrosterol and a formal synthesis of aragusterols, JCS Perkin I, 1996,
2291ꢀ2296.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6. Kha, H.T.; Basseri, B.; Shouhed, D.; Richardson, J.; Tetradis, S.;
Hahn, T.J.; Parhami, F. Oxysterols regulate differentiation of mesenꢀ
chymal stem cells: proꢀbone and antiꢀfat. J. Bone Miner. Res. 2004,
19, 830ꢀ840.
7. Aghaloo, T. L.; Amantea, C. M.; Cowan, C. M.; Richardson, J. A.;
Wu, B.M. Parhami, F.; Tetradis, S. Oxysterols enhance osteoblast
differentiation in vitro and bone healing in vivo. J. Orthop. Res. 2007,
25, 1488ꢀ1497.
8. Giannoudis, P. V.; Dinopoulos, H.; Tsiridis, E. Bone substitutes: an
update. Injury 2005, 36, S20ꢀS27.
9. Olkkonen, V.A.; Beaslas, O.; Nissila, E. Oxysterols and their celluꢀ
lar effectors. Biomolecules 2012, 2, 76ꢀ103.
10. Johnson, J.S.; Meliton, V.; Kim, W.K.; Lee, K.ꢀB.; Wang, J.C.;
Nguyen, K.; Yoo, D.; Jung, M.E.; Atti, E.; Tetradis, S.; Pereira, R.C.;
Magyar, C.; Nargizyan, T.; Hahn, T.J.; Farouz, F.; Thies, S.; Parhami,
F. Novel oxysterols have proꢀosteogenic and antiꢀadipogenic effects
in vitro and induce spinal fusion in vivo. J. Cell. Biochem. 2011, 112,
1673ꢀ1684.
11. LeBlanc, M. A. and McMaster, C. R. Lipid binding requirements
for oxysterolꢀbinding protein Kes1 inhibition of autophagy and endoꢀ
someꢀtransꢀGlogi trafficking pathways. J. Biol. Chem. 2010, 285,
33875ꢀ33884.
12. Peet, D.J.; Janowski, B.A.; Mangelsdorf, D.J. The LXRs: a new
class of oxysterol receptors. Curr. Opin. Genet. Dev. 2008, 8, 571ꢀ
575.
13. Liu, C.; Yang, X. V.; Wu, J.; Kuei, C.; Mani, N. S.; Zhang, L.;
Yu, J.; Sutton, S. W.; Qin, N.; Banie, H.; Karlsson, L.; Sun, S.; Lovꢀ
enberg, T. W. Oxysterols direct Bꢀcell migration through EBI2. Na-
ture 2011, 475, 519ꢀ523.
14. Peet, D.J.; Janowski, B.A.; Mangelsdorf, D.J. The LXRs: a new
class of oxysterol receptors. Curr. Opin. Genet. Dev. 2008, 8, 571ꢀ
575.
15. Kim, W.ꢀK.; Meliton, V.; Park, K.W.; Hong, C.H.; Tontonoz, P.;
Niewiadomski, P.; Waschek, J.A.; Tetradis, S.; Parhami, F. Negative
regulation of hedgehog signaling by liver X receptors. Mol. Endo-
crinol. 2009, 23, 1532ꢀ1543.
16. Janowski, B.A.; Willy, P.J.; Devi, T.R.; Falck, J.R.; Mangelsdorf,
D.J. An oxysterol signaling pathway mediated by the nuclear receptor
LXRα. Nature 1996, 383, 728ꢀ731.
17. Janowski, B.A.; Grogan, M.J.; Jones, S.A.; Wisely, G.B.; Kliewer,
S.A.; Corey, E.J.; Mangelsdorf, D.J. Structural requirements of ligꢀ
ands for the oxysterol liver X receptors LXRα and LXRβ. Proc. Natl.
Acad. Sci. 1999, 96, 266ꢀ271.
27. Parhami, F.; Jung, M.E.; Nguyen, K.T.; Matsui, W.; Yoo, D. Meꢀ
liton, V. Oxysterols that activate liver X receptor signaling and inhibit
hedgehog signaling. WO 2011103175. 2011.
28. Nachtergaele, S.; Mydock, L.K.; Krishnan, K.; Rammohan, J.;
Schlesinger, P.H.; Covey, D.F.; Rohatgi, R. Oxysterols are allosteric
activators of the oncoprotein smoothened. Nat. Chem. Biol. 2012, 8,
211ꢀ220.
18. Baggiolini, E.G.; Baggiolini, B.J.; Hennessy, B.M.; Shiuey, SꢀJ.:
Truitt, G.A. Uskokovic, M.R.; Vitamin D3 analogs, U.S. Patent
5,087,619, 1992.
19. DeLuca, H.F.; Bulli, P.T.; Plum, L.A.; ClagettꢀDame, M. 2ꢀ
Methyleneꢀ(20E)ꢀ20(22)ꢀdehydroꢀ19ꢀnorꢀvitamin
D analogs. U.S.
Patent Application 2010/009940A1, 2010.
20. Kametani, T.; Katoh, T.; Tsubuki, M.; Honda, T. A facile preparaꢀ
tion of ecdysone side chain by utilizing furan derivative. Chemistry
Letters, 1985, 485ꢀ488.
21. Kametani, T.; Tsubuki, M.; Nemoto, H. A novel synthetic apꢀ
proach to the exdysone sideꢀchain via furan derivatives. JCS Perkin I,
1981, 3077ꢀ3082.
22. Jones, S.R.; Kinney, W.A.; Zhang, X; Jones, L.M.; Selinsky, B.S.
The synthesis and characterization of analogs of the antimicrobial
ACS Paragon Plus Environment