27. Yoshida M, Kijima M, Akita M et al (1990) Potent and specific inhibition of mammalian
histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265:17174–17179
28. Richon VM, Emiliani S, Verdin E et al (1998) A class of hybrid polar inducers of transformed
cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A 95:3003–3007
29. Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone
deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25:84–90
30. Kawai K, Nagata N (2012) Metal–ligand interactions: an analysis of zinc binding groups using
the Protein Data Bank. Eur J Med Chem 51:271–276
31. Shen S, Kozikowski AP (2016) Why hydroxamates may not be the best histone deacetylase
inhibitors – what some may have forgotten or would rather forget? ChemMedChem 11:15–21
32. Finn PW, Loza E, Carstensten E (2016) The discovery and development of belinostat. In:
Fischer J, Childers WE (eds) Successful drug discovery, vol 2. Wiley-VCH, Weinheim, pp
31–57
33. Atadja P, Perez L (2016) Discovery and development of Farydak (NVP-LBH589,
panobinostat) as an anticancer drug. In: Fischer J, Childers WE (eds) Successful drug
discovery, vol 2. Wiley-VCH, Weinheim, pp 59–88
34. Maolanon AR, Madsen AS, Olsen CA (2016) Innovative strategies for selective inhibition of
histone deacetylases. Cell Chem Biol 23:759–768
35. Novotny-Diermayr V, Sangthongpitag K, Hu CY et al (2010) SB939, a novel potent and orally
active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of
colorectal cancer. Mol Cancer Ther 9:642–652
36. Mandl-Weber S, Meinel FG, Jankowsky R et al (2010) The novel inhibitor of histone
deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple
myeloma (MM) cells. Br J Haematol 149:518–528
37. Leoni F, Fossati G, Lewis EC et al (2005) The histone deacetylase inhibitor ITF2357 reduces
production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol
Med 11:1–15
38. Buggy JJ, Cao ZA, Bass KE et al (2006) CRA-024781: a novel synthetic inhibitor of histone
deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther
5:1309–1317
39. Lu Q, Wang DS, Chen CS et al (2005) Structure-based optimization of phenylbutyrate-derived
histone deacetylase inhibitors. J Med Chem 48:5530–5535
40. Arts J, King P, Mariën A et al (2009) JNJ-26481585, a novel “second-generation” oral histone
deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res
15:6841–6851
41. Moffat D, Patel S, Day F et al (2010) Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]
amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a class I
selective orally active histone deacetylase inhibitor. J Med Chem 53:8663–8678
42. Santo L, Hideshima T, Kung AL et al (2012) Preclinical activity, pharmacodynamic, and
pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with
bortezomib in multiple myeloma. Blood 119:2579–2589
43. Huang P, Almeciga-Pinto I, Jarpe M et al (2017) Selective HDAC inhibition by ACY-241
enhances the activity of paclitaxel in solid tumor models. Oncotarget 8:2694–2707
44. Lecointre B, Narozny R, Borrello MT et al (2018) Isoform-selective HDAC1/6/8 inhibitors
with an imidazo-ketopiperazine cap containing stereochemical diversity. Philos Trans R Soc B
373:20170364
45. Gaisina IN, Tueckmantel W, Ugolkov A et al (2016) Identification of HDAC6-selective
inhibitors of low cancer cell cytotoxicity. ChemMedChem 11:81–92
46. Sellmer A, Stangl H, Beyer M et al (2018) Marbostat-100 defines a new class of potent and
selective antiinflammatory and antirheumatic histone deacetylase 6 inhibitors. J Med Chem
61:3454–3477
47. Balasubramanian S, Ramos J, Luo W et al (2008) A novel histone deacetylase 8 (HDAC8)specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. Leukemia 22:1026–1034
Targeting the Zinc-Dependent Histone Deacetylases (HDACs) for Drug Discovery
23
histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265:17174–17179
28. Richon VM, Emiliani S, Verdin E et al (1998) A class of hybrid polar inducers of transformed
cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci U S A 95:3003–3007
29. Marks PA, Breslow R (2007) Dimethyl sulfoxide to vorinostat: development of this histone
deacetylase inhibitor as an anticancer drug. Nat Biotechnol 25:84–90
30. Kawai K, Nagata N (2012) Metal–ligand interactions: an analysis of zinc binding groups using
the Protein Data Bank. Eur J Med Chem 51:271–276
31. Shen S, Kozikowski AP (2016) Why hydroxamates may not be the best histone deacetylase
inhibitors – what some may have forgotten or would rather forget? ChemMedChem 11:15–21
32. Finn PW, Loza E, Carstensten E (2016) The discovery and development of belinostat. In:
Fischer J, Childers WE (eds) Successful drug discovery, vol 2. Wiley-VCH, Weinheim, pp
31–57
33. Atadja P, Perez L (2016) Discovery and development of Farydak (NVP-LBH589,
panobinostat) as an anticancer drug. In: Fischer J, Childers WE (eds) Successful drug
discovery, vol 2. Wiley-VCH, Weinheim, pp 59–88
34. Maolanon AR, Madsen AS, Olsen CA (2016) Innovative strategies for selective inhibition of
histone deacetylases. Cell Chem Biol 23:759–768
35. Novotny-Diermayr V, Sangthongpitag K, Hu CY et al (2010) SB939, a novel potent and orally
active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of
colorectal cancer. Mol Cancer Ther 9:642–652
36. Mandl-Weber S, Meinel FG, Jankowsky R et al (2010) The novel inhibitor of histone
deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple
myeloma (MM) cells. Br J Haematol 149:518–528
37. Leoni F, Fossati G, Lewis EC et al (2005) The histone deacetylase inhibitor ITF2357 reduces
production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol
Med 11:1–15
38. Buggy JJ, Cao ZA, Bass KE et al (2006) CRA-024781: a novel synthetic inhibitor of histone
deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther
5:1309–1317
39. Lu Q, Wang DS, Chen CS et al (2005) Structure-based optimization of phenylbutyrate-derived
histone deacetylase inhibitors. J Med Chem 48:5530–5535
40. Arts J, King P, Mariën A et al (2009) JNJ-26481585, a novel “second-generation” oral histone
deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res
15:6841–6851
41. Moffat D, Patel S, Day F et al (2010) Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]
amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a class I
selective orally active histone deacetylase inhibitor. J Med Chem 53:8663–8678
42. Santo L, Hideshima T, Kung AL et al (2012) Preclinical activity, pharmacodynamic, and
pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with
bortezomib in multiple myeloma. Blood 119:2579–2589
43. Huang P, Almeciga-Pinto I, Jarpe M et al (2017) Selective HDAC inhibition by ACY-241
enhances the activity of paclitaxel in solid tumor models. Oncotarget 8:2694–2707
44. Lecointre B, Narozny R, Borrello MT et al (2018) Isoform-selective HDAC1/6/8 inhibitors
with an imidazo-ketopiperazine cap containing stereochemical diversity. Philos Trans R Soc B
373:20170364
45. Gaisina IN, Tueckmantel W, Ugolkov A et al (2016) Identification of HDAC6-selective
inhibitors of low cancer cell cytotoxicity. ChemMedChem 11:81–92
46. Sellmer A, Stangl H, Beyer M et al (2018) Marbostat-100 defines a new class of potent and
selective antiinflammatory and antirheumatic histone deacetylase 6 inhibitors. J Med Chem
61:3454–3477
47. Balasubramanian S, Ramos J, Luo W et al (2008) A novel histone deacetylase 8 (HDAC8)specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. Leukemia 22:1026–1034
Targeting the Zinc-Dependent Histone Deacetylases (HDACs) for Drug Discovery
23