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124. Schiedel M, Rumpf T, Karaman B et al (2016) Aminothiazoles as potent and selective Sirt2
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org/10.1021/acs.jmedchem.5b01517
125. Yang L, Ma X, Yuan C et al (2017) Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-Nphenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors. Eur J Med
Chem 134:230–241. https://doi.org/10.1016/j.ejmech.2017.04.010
126. Schiedel M, Herp D, Hammelmann S, Swyter S, Lehotzky A, Robaa D, Oláh J, Ovádi J, Sippl
W, Jung M (2017) Chemically induced degradation of sirtuin 2 (Sirt2) by a proteolysis
targeting chimera (PROTAC) based on sirtuin rearranging ligands (SirReals). J Med Chem
61(2):482–491. https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b01872
127. Outeiro TF, Kontopoulos E, Altmann SM (2007) Sirtuin 2 inhibitors rescue alpha-synucleinmediated toxicity in models of Parkinson’s disease. Science 317(5837):516–519. https://doi.
org/10.1126/science.1143780
128. Zhang X, Smith DL, Meriin AB et al (2005) A potent small molecule inhibits polyglutamine
aggregation in Huntington’s disease neurons and suppresses neurodegeneration in vivo. Proc
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129. Bodner RA, Outeiro TF, Atlmann S et al (2006) Pharmacological promotion of inclusion
formation: a therapeutic approach for Huntington’s and Parkinson’s diseases. Proc Natl Acad
Sci U S A 103(11):4246–4251. https://doi.org/10.1073/pnas.0511256103
88
M. Rahnasto-Rilla et al.
and suppresses tumour growth through activation of p53. EMBO Mol Med 4(4):298–312.
https://doi.org/10.1002/emmm.201100211
115. Panathur N, Dalimba U, Koushik PV et al (2013) Identification and characterization of novel
indole based small molecules as anticancer agents through SIRT1 inhibition. Eur J Med Chem
69:125–138. https://doi.org/10.1016/j.ejmech.2013.08.018
116. Panathur N, Gokhale N, Dalimba U et al (2015) New indole-isoxazolone derivatives:
synthesis, characterisation and in vitro SIRT1 inhibition studies. Bioorg Med Chem Lett
25(14):2768–2772. https://doi.org/10.1016/j.bmcl.2015.05.015
117. Therrien E, Laourche G, Nguyen N et al (2015) Discovery of bicyclic pyrazoles as class III
histone deacetylase SIRT1 and SIRT2 inhibitors. Bioorg Med Chem Lett 25(12):2514–2518.
https://doi.org/10.1016/j.bmcl.2015.04.068
118. Fridén-Saxin M, Seifert T, Landergren MR (2012) Synthesis and evaluation of substituted
chroman-4-one and chromone derivatives as sirtuin 2-selective inhibitors. J Med Chem
55(16):7104–7113. https://doi.org/10.1021/jm3005288
119. Seifert T, Malo M, Kokkola T et al (2014) Chroman-4-one- and chromone-based sirtuin
2 inhibitors with antiproliferative properties in cancer cells. J Med Chem 57(23):9870–9888.
https://doi.org/10.1021/jm500930h
120. Seifert T, Malo M, Lengqvist J et al (2016) Identification of the binding site of chroman-4-onebased Sirtuin 2-Sselective inhibitors using photoaffinity labeling in combination with tandem
mass spectrometry. J Med Chem 59(23):10794–10799. https://doi.org/10.1021/acs.jmedchem.
6b01117
121. Schnekenburger M, Goffin E, Lee JY et al (2017) Discovery and characterization of R/S-N-3cyanophenyl-N
0 -(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4yl)urea, a new histone deacetylase class III inhibitor exerting antiproliferative activity against
cancer cell lines. J Med Chem 60(11):4714–4733. https://doi.org/10.1021/acs.jmedchem.
7b00533
122. Rumpf T, Schiedel M, Karaman B et al (2015) Selective Sirt2 inhibition by ligand-induced
rearrangement of the active site. Nat Commun 6:6263. https://doi.org/10.1038/ncomms7263
123. Kiviranta PH, Salo HS, Leppänen J et al (2008) Characterization of the binding properties of
SIRT2 inhibitors with a N-(3-phenylpropenoyl)-glycine tryptamide backbone. Bioorg Med
Chem 16(17):8054–8062. https://doi.org/10.1016/j.bmc.2008.07.059
124. Schiedel M, Rumpf T, Karaman B et al (2016) Aminothiazoles as potent and selective Sirt2
inhibitors: a structure-activity relationship study. J Med Chem 59(4):1599–1612. https://doi.
org/10.1021/acs.jmedchem.5b01517
125. Yang L, Ma X, Yuan C et al (2017) Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)-Nphenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors. Eur J Med
Chem 134:230–241. https://doi.org/10.1016/j.ejmech.2017.04.010
126. Schiedel M, Herp D, Hammelmann S, Swyter S, Lehotzky A, Robaa D, Oláh J, Ovádi J, Sippl
W, Jung M (2017) Chemically induced degradation of sirtuin 2 (Sirt2) by a proteolysis
targeting chimera (PROTAC) based on sirtuin rearranging ligands (SirReals). J Med Chem
61(2):482–491. https://pubs.acs.org/doi/10.1021/acs.jmedchem.6b01872
127. Outeiro TF, Kontopoulos E, Altmann SM (2007) Sirtuin 2 inhibitors rescue alpha-synucleinmediated toxicity in models of Parkinson’s disease. Science 317(5837):516–519. https://doi.
org/10.1126/science.1143780
128. Zhang X, Smith DL, Meriin AB et al (2005) A potent small molecule inhibits polyglutamine
aggregation in Huntington’s disease neurons and suppresses neurodegeneration in vivo. Proc
Natl Acad Sci U S A 102(3):892–897. https://doi.org/10.1073/pnas.0408936102
129. Bodner RA, Outeiro TF, Atlmann S et al (2006) Pharmacological promotion of inclusion
formation: a therapeutic approach for Huntington’s and Parkinson’s diseases. Proc Natl Acad
Sci U S A 103(11):4246–4251. https://doi.org/10.1073/pnas.0511256103
88
M. Rahnasto-Rilla et al.