20. Richon VM, Webb Y, Merger R, Sheppard T, Jursic B, Ngo L, Civoli F, Breslow R, Rifkind
RA, Marks PA (1996) Second generation hybrid polar compounds are potent inducers of
transformed cell differentiation. PNAS 93(12):5705–5708
21. Yoshida M, Kijima M, Akita M, Beppu T (1990) Potent and specific inhibition of mammalian
histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265(28):
17174–17179
22. Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T (1993) Trapoxin, an antitumor cyclic
tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem
268(30):22429–22435
23. Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this
histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25(1):84–90
24. Zagni C, Floresta G, Monciino G, Rescifina A (2017) The search for potent, small-molecule
HDAC is in cancer treatment: a decade after vorinostat. Med Res Rev 37(6):1373–1428
25. Jung M, Hoffmann K, Brosch G, Loidl P (1997) Analogues of trichosтatin A and trapoxin B as
histone deacetylase inhibitors. Bioorg Med Chem Lett 7(13):1655–1658
26. Maolanon AR, Madsen AS, Olsen CA (2016) Innovative strategies for selective inhibition of
histone deacetylases. Cell Chem Biol 23(7):759–768
27. Gantt SML, Decroos C, Lee MS, Gullett LE, Bowman CM, Christianson DW, Fierke CA
(2016) General base–general acid catalysis in human histone deacetylase 8. Biochemistry
55(5):820–832
28. Decroos C, Christianson NH, Gullett LE, Bowman CM, Christianson KE, Deardorff MA,
Christianson DW (2015) Biochemical and structural characterization of HDAC8 mutants
associated with cornelia de lange syndrome spectrum disorders. Biochemistry 54(42):
6501–6513
29. Dowling DP, Gantt SL, Gattis SG, Fierke CA, Christianson DW (2008) Structural studies of
human histone deacetylase 8 and its site-specific variants complexed with substrate and
inhibitors. Biochemistry 47(51):13554–13563
30. Lauffer BE, Mintzer R, Fong R, Mukund S, Tam C, Zilberleyb I, Flicke B, Ritscher A,
Fedorowicz G, Vallero R, Ortwine DF, Gunzner J, Modrusan Z, Neumann L, Koth CM,
Lupardus PJ, Kaminker JS, Heise CE, Steiner P (2013) Histone deacetylase (HDAC) inhibitor
kinetic rate constants correlate with cellular histone acetylation but not transcription and
cell viability. J Biol Chem 288(37):26926–26943
31. Porter NJ, Mahendran A, Breslow R, Christianson DW (2017) Unusual zinc-binding mode of
HDAC6-selective hydroxamate inhibitors. PNAS 114(51):13459–13464
32. Gupta SP (2015) QSAR studies on hydroxamic acids: a fascinating family of chemicals with a
wide spectrum of activities. Chem Rev 115(13):6427–6490
33. Chen K, Xu L, Wiest O (2013) Computational exploration of zinc binding groups for HDAC
inhibition. J Org Chem 78(10):5051–5055
34. Wang D, Helquist P, Wiest O (2007) Zinc binding in HDAC inhibitors: a DFT study. J Org
Chem 72(14):5446–5449
35. Wang D-F, Wiest O, Helquist P, Lan-Hargest H-Y, Wiech NL (2004) QSAR studies of PC-3
cell line inhibition activity of TSA and SAHA-like hydroxamic acids. Bioorg Med Chem Lett
14(3):707–711
36. Kalyaanamoorthy S, Chen Y-PP (2013) Quantum polarized ligand docking investigation to
understand the significance of protonation states in histone deacetylase inhibitors. J Mol Graph
Model 44:44–53
37. Wu R, Lu Z, Cao Z, Zhang Y (2011) Zinc chelation with hydroxamate in histone deacetylases
modulated by water access to the linker binding channel. J Am Chem Soc 133(16):6110–6113
38. Cross JB, Duca JS, Kaminski JJ, Madison VS (2002) The active site of a zinc-dependent
metalloproteinase influences the computed P K a of ligands coordinated to the catalytic zinc ion.
J Am Chem Soc 124(37):11004–11007
39. Gong W, Wu R, Zhang Y (2015) Thiol versus hydroxamate as zinc binding group in
HDAC inhibition: an Ab initio QM/MM molecular dynamics study. J Comput Chem 36(30):
2228–2235
50
C. Moreno-Yruela and C. A. Olsen
RA, Marks PA (1996) Second generation hybrid polar compounds are potent inducers of
transformed cell differentiation. PNAS 93(12):5705–5708
21. Yoshida M, Kijima M, Akita M, Beppu T (1990) Potent and specific inhibition of mammalian
histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265(28):
17174–17179
22. Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T (1993) Trapoxin, an antitumor cyclic
tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem
268(30):22429–22435
23. Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this
histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25(1):84–90
24. Zagni C, Floresta G, Monciino G, Rescifina A (2017) The search for potent, small-molecule
HDAC is in cancer treatment: a decade after vorinostat. Med Res Rev 37(6):1373–1428
25. Jung M, Hoffmann K, Brosch G, Loidl P (1997) Analogues of trichosтatin A and trapoxin B as
histone deacetylase inhibitors. Bioorg Med Chem Lett 7(13):1655–1658
26. Maolanon AR, Madsen AS, Olsen CA (2016) Innovative strategies for selective inhibition of
histone deacetylases. Cell Chem Biol 23(7):759–768
27. Gantt SML, Decroos C, Lee MS, Gullett LE, Bowman CM, Christianson DW, Fierke CA
(2016) General base–general acid catalysis in human histone deacetylase 8. Biochemistry
55(5):820–832
28. Decroos C, Christianson NH, Gullett LE, Bowman CM, Christianson KE, Deardorff MA,
Christianson DW (2015) Biochemical and structural characterization of HDAC8 mutants
associated with cornelia de lange syndrome spectrum disorders. Biochemistry 54(42):
6501–6513
29. Dowling DP, Gantt SL, Gattis SG, Fierke CA, Christianson DW (2008) Structural studies of
human histone deacetylase 8 and its site-specific variants complexed with substrate and
inhibitors. Biochemistry 47(51):13554–13563
30. Lauffer BE, Mintzer R, Fong R, Mukund S, Tam C, Zilberleyb I, Flicke B, Ritscher A,
Fedorowicz G, Vallero R, Ortwine DF, Gunzner J, Modrusan Z, Neumann L, Koth CM,
Lupardus PJ, Kaminker JS, Heise CE, Steiner P (2013) Histone deacetylase (HDAC) inhibitor
kinetic rate constants correlate with cellular histone acetylation but not transcription and
cell viability. J Biol Chem 288(37):26926–26943
31. Porter NJ, Mahendran A, Breslow R, Christianson DW (2017) Unusual zinc-binding mode of
HDAC6-selective hydroxamate inhibitors. PNAS 114(51):13459–13464
32. Gupta SP (2015) QSAR studies on hydroxamic acids: a fascinating family of chemicals with a
wide spectrum of activities. Chem Rev 115(13):6427–6490
33. Chen K, Xu L, Wiest O (2013) Computational exploration of zinc binding groups for HDAC
inhibition. J Org Chem 78(10):5051–5055
34. Wang D, Helquist P, Wiest O (2007) Zinc binding in HDAC inhibitors: a DFT study. J Org
Chem 72(14):5446–5449
35. Wang D-F, Wiest O, Helquist P, Lan-Hargest H-Y, Wiech NL (2004) QSAR studies of PC-3
cell line inhibition activity of TSA and SAHA-like hydroxamic acids. Bioorg Med Chem Lett
14(3):707–711
36. Kalyaanamoorthy S, Chen Y-PP (2013) Quantum polarized ligand docking investigation to
understand the significance of protonation states in histone deacetylase inhibitors. J Mol Graph
Model 44:44–53
37. Wu R, Lu Z, Cao Z, Zhang Y (2011) Zinc chelation with hydroxamate in histone deacetylases
modulated by water access to the linker binding channel. J Am Chem Soc 133(16):6110–6113
38. Cross JB, Duca JS, Kaminski JJ, Madison VS (2002) The active site of a zinc-dependent
metalloproteinase influences the computed P K a of ligands coordinated to the catalytic zinc ion.
J Am Chem Soc 124(37):11004–11007
39. Gong W, Wu R, Zhang Y (2015) Thiol versus hydroxamate as zinc binding group in
HDAC inhibition: an Ab initio QM/MM molecular dynamics study. J Comput Chem 36(30):
2228–2235
50
C. Moreno-Yruela and C. A. Olsen