Research Groups‎ > ‎

NEVERLAB (CHIM/08)

Head of Laboratory: Prof. Antonello Mai

Main research topics:

Prof Mai and his team have long and validated experience in epigenetics medicinal chemistry research and in managing collaborations for biochemical, biological and preclinical studies. Within his group various projects aimed to develop small molecules (inhibitors and/or activators) for various mainly epigenetic targets as well as modulators of protein-protein interactions, are conducted applying a multiple approach bringing synthetic organic chemistry, medicinal chemistry, chemical biology, biochemistry and biophysics together. Specifically, in the last years they focused, demonstrated in numerous publications, mainly on the design, synthesis and development of small epigenetic modulators of HDACs, SIRTs, HMTs, KDMs, DNMTs for a new approach to anticancer chemotherapy, neurodegenerative and metabolic pathologies, as well as anti-parasitic treatment.
Prof Mai’s team has not only a broad and specific experience in drug design but also in synthetic chemistry through applying low cost and eco-friendly modern synthetic chemistry such as flow- and click chemistry in order to obtain their small modulators of the aforementioned targets.
Their specific expertise in drug design helps them to assure the production of important outcomes and to overcome possible difficulties throughout the development process

National and International Collaborations:
The group of Prof Mai has more than 60 active research collaborators inside and outside Italy. The following list names just a few but is far from exhaustive:
Prof Lucia Altucci (Naples, Italy), Prof Andrea Mattevi (Pavia, Italy), Prof Gianluca Sbardella (Salerno, Italy), Dr Donatella Del Bufalo (IFO, Roma), Dr Daniela Trisciuoglio (CNR, Roma), Dr. Rossella Rota (OPBG, Roma), Prof Saverio Minucci (IEO, Milano), Prof Pier G Pelicci (IEO, Milano), Prof Clemens Steegborn (Bayreuth, Germany), Prof Manfred Jung (Freiburg, Germany), Prof Roland Schüle (Freiburg, Germany), Prof Wolfgang Sippl (Jena, Germany), Prof Gerald Spaeth (Paris, France), Dr. Paola Arimondo (Paris, France), Prof Stuart Conway (Oxford, UK), Prof Paul Brennan (Oxford, UK), Prof Kate Andrews (Brisbane, Australia), Prof Philip Cole (Boston, USA).

Facilities:
The group of Prof Mai has access to the following instruments for organic synthesis and characterization: UV Perkin-Elmer 552 Spectrophotometer, NMR Bruker AC400 Spectrometer, Thermo Fisher HPLC and Mass spectrometer, PARR Hydrogenator, Stuart melting point apparatus, Biotage microwave reactor, Biotage Automated flash chromatography and Perkin Elmer EnSpire multimode plate reader.

ERC panels:
LS (examples: LS2_8 Epigenetics and gene regulation;
LS7_3 Pharmacology, pharmacogenomics, drug discovery and design, drug therapy;
LS4_6 Cancer and its biological basis)

Grants (2015-2018):
AIRC 2016, PRIN2015, Ateneo project, EU-funding: FP7: BLUEPRINT (contract n° 282510), A-PARADDISE (contract n° 602080),

Laboratory Members:

Dr. Dante Rotili (RU)
Dr. Sergio Valente (RTD-B)
Dr. Alessia Lucidi (postdoctoral fellowship holder)
Dr. Giulia Stazi (postdoctoral fellowship holder)
Dr. Clemens Zwergel (postdoctoral fellowship holder)
Roberta Mazzone (PhD student)
Annalisa Romanelli (PhD student)
Daniela Tomaselli (PhD student)

Publications (2015-2018):

1. Fiorentino F, Mai A, Rotili D. Lysine acetyltransferase inhibitors: structure-activity relationships and potential therapeutic implications. Future Med Chem. 2018 Apr 20. doi: 10.4155/fmc-2017-0244. [Epub ahead of print] PubMed PMID: 29676588.

2. Cocco E, Leo M, Canzonetta C, Di Vito S, Mai A, Rotili D, Di Napoli A, Vecchione A, De Nunzio C, Filetici P, Stoppacciaro A. KAT3B-p300 and H3AcK18/H3AcK14 levels are prognostic markers for kidney ccRCC tumor aggressiveness and target of KAT inhibitor CPTH2. Clin Epigenetics. 2018 Apr 4;10:44. doi: 10.1186/s13148-018-0473-4. eCollection 2018. PubMed PMID: 29632619; PubMed Central PMCID: PMC5885315.

3. Buonvicino D, Felici R, Ranieri G, Caramelli R, Lapucci A, Cavone L, Muzzi M, Di Pietro L, Bernardini C, Zwergel C, Valente S, Mai A, Chiarugi A. Effects of Class II-Selective Histone Deacetylase Inhibitor on Neuromuscular Function and Disease Progression in SOD1-ALS Mice. Neuroscience. 2018 Mar 26;379:228-238. doi: 10.1016/j.neuroscience.2018.03.022. [Epub ahead of print] PubMed PMID: 29588251.

4. Carafa V, Nebbioso A, Cuomo F, Rotili D, Cobellis G, Bontempo P, Baldi A, Spugnini EP, Citro G, Chambery A, Russo R, Ruvo M, Ciana P, Maravigna L, Shaik J, Radaelli E, De Antonellis P, Tarantino D, Pirolli A, Ragno R, Zollo M, Stunnenberg HG, Mai A, Altucci L. RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer. Clin Cancer Res. 2018 Mar 13. pii: clincanres.3081.2017. doi: 10.1158/1078-0432.CCR-17-3081. [Epub ahead of print] PubMed PMID: 29535128.

5. Sabatino M, Rotili D, Patsilinakos A, Forgione M, Tomaselli D, Alby F, Arimondo PB, Mai A, Ragno R. Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non-nucleoside inhibitors by means of ligand-based and structure-based approaches. J Comput Aided Mol Des. 2018 Mar;32(3):435-458. doi: 10.1007/s10822-018-0096-z. Epub 2018 Jan 15. PubMed PMID: 29335872.

6. Kalin JH, Wu M, Gomez AV, Song Y, Das J, Hayward D, Adejola N, Wu M, Panova I, Chung HJ, Kim E, Roberts HJ, Roberts JM, Prusevich P, Jeliazkov JR, Roy Burman SS, Fairall L, Milano C, Eroglu A, Proby CM, Dinkova-Kostova AT, Hancock WW, Gray JJ, Bradner JE, Valente S, Mai A, Anders NM, Rudek MA, Hu Y, Ryu B, Schwabe JWR, Mattevi A, Alani RM, Cole PA. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nat Commun. 2018 Jan 4;9(1):53. doi: 10.1038/s41467-017-02242-4. PubMed PMID: 29302039; PubMed Central PMCID: PMC5754352.

7. Pannek M, Simic Z, Fuszard M, Meleshin M, Rotili D, Mai A, Schutkowski M, Steegborn C. Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features. Nat Commun. 2017 Nov 15;8(1):1513. doi: 10.1038/s41467-017-01701-2. PubMed PMID: 29138502; PubMed Central PMCID: PMC5686155.

8. Miele E, Valente S, Alfano V, Silvano M, Mellini P, Borovika D, Marrocco B, Po A, Besharat ZM, Catanzaro G, Battaglia G, Abballe L, Zwergel C, Stazi G, Milite C, Castellano S, Tafani M, Trapencieris P, Mai A, Ferretti E. The histone methyltransferase EZH2 as a druggable target in SHH medulloblastoma cancer stem cells. Oncotarget. 2017 Aug 2;8(40):68557-68570. doi: 10.18632/oncotarget.19782. eCollection 2017 Sep 15. PubMed PMID: 28978137; PubMed Central PMCID: PMC5620277.

9. Lapucci A, Cavone L, Buonvicino D, Felici R, Gerace E, Zwergel C, Valente S, Mai A, Chiarugi A. Effect of Class II HDAC inhibition on glutamate transporter expression and survival in SOD1-ALS mice. Neurosci Lett. 2017 Aug 24;656:120-125. doi: 10.1016/j.neulet.2017.07.033. Epub 2017 Jul 19. PubMed PMID: 28732762.

10. Mazzone R, Zwergel C, Mai A, Valente S. Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy. Clin Epigenetics. 2017 May 30;9:59. doi: 10.1186/s13148-017-0358-y. eCollection 2017. Review. PubMed PMID: 28572863; PubMed Central PMCID: PMC5450222.

11. Wapenaar H, van den Bosch T, Leus NGJ, van der Wouden PE, Eleftheriadis N, Hermans J, Hailu GS, Rotili D, Mai A, Dömling A, Bischoff R, Haisma HJ, Dekker FJ. The relevance of K(i) calculation for bi-substrate enzymes illustrated by kinetic evaluation of a novel lysine (K) acetyltransferase 8 inhibitor. Eur J Med Chem. 2017 Aug 18;136:480-486. doi: 10.1016/j.ejmech.2017.05.015. Epub 2017 May 5. PubMed PMID: 28527406; PubMed Central PMCID: PMC5720340.

12. Zwergel C, Czepukojc B, Evain-Bana E, Xu Z, Stazi G, Mori M, Patsilinakos A, Mai A, Botta B, Ragno R, Bagrel D, Kirsch G, Meiser P, Jacob C, Montenarh M, Valente S. Novel coumarin- and quinolinone-based polycycles as cell division cycle 25-A and -C phosphatases inhibitors induce proliferation arrest and apoptosis in cancer cells. Eur J Med Chem. 2017 Jul 7;134:316-333. doi: 10.1016/j.ejmech.2017.04.012. Epub 2017 Apr 10. PubMed PMID: 28431339.

13. Coni S, Mancuso AB, Di Magno L, Sdruscia G, Manni S, Serrao SM, Rotili D, Spiombi E, Bufalieri F, Petroni M, Kusio-Kobialka M, De Smaele E, Ferretti E, Capalbo C, Mai A, Niewiadomski P, Screpanti I, Di Marcotullio L, Canettieri G. Corrigendum: Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma. Sci Rep. 2017 Apr 21;7:46645. doi: 10.1038/srep46645. PubMed PMID: 28429760; PubMed Central PMCID: PMC5399352.

14. Stazi G, Zwergel C, Mai A, Valente S. EZH2 inhibitors: a patent review (2014-2016). Expert Opin Ther Pat. 2017 Jul;27(7):797-813. doi:10.1080/13543776.2017.1316976. Epub 2017 Apr 20. Review. PubMed PMID: 28394193.

15. Madia VN, Benedetti R, Barreca ML, Ngo L, Pescatori L, Messore A, Pupo G,Saccoliti F, Valente S, Mai A, Scipione L, Zheng YG, Tintori C, Botta M,Cecchetti V, Altucci L, Di Santo R, Costi R. Structure-Activity Relationships on Cinnamoyl Derivatives as Inhibitors of p300 Histone Acetyltransferase.ChemMedChem. 2017 Aug 22;12(16):1359-1368. doi: 10.1002/cmdc.201700040. Epub 2017Apr 12. PubMed PMID: 28346821.

16. Coni S, Mancuso AB, Di Magno L, Sdruscia G, Manni S, Serrao SM, Rotili D, Spiombi E, Bufalieri F, Petroni M, Kusio-Kobialka M, De Smaele E, Ferretti E, Capalbo C, Mai A, Niewiadomski P, Screpanti I, Di Marcotullio L, Canettieri G. Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma. Sci Rep. 2017 Mar 9;7:44079. doi: 10.1038/srep44079. PubMed PMID: 28276480; PubMed Central PMCID: PMC5343431.

17. Hailu GS, Robaa D, Forgione M, Sippl W, Rotili D, Mai A. Lysine Deacetylase Inhibitors in Parasites: Past, Present, and Future Perspectives. J Med Chem. 2017 Jun 22;60(12):4780-4804. doi: 10.1021/acs.jmedchem.6b01595. Epub 2017 Mar 15. Review. PubMed PMID: 28241112.

18. Moniot S, Forgione M, Lucidi A, Hailu GS, Nebbioso A, Carafa V, Baratta F, Altucci L, Giacché N, Passeri D, Pellicciari R, Mai A, Steegborn C, Rotili D. Development of 1,2,4-Oxadiazoles as Potent and Selective Inhibitors of the Human Deacetylase Sirtuin 2: Structure-Activity Relationship, X-ray Crystal Structure, and Anticancer Activity. J Med Chem. 2017 Mar 23;60(6):2344-2360. doi:10.1021/acs.jmedchem.6b01609. Epub 2017 Mar 14. PubMed PMID: 28240897.

19. Palanisamy SK, Trisciuoglio D, Zwergel C, Del Bufalo D, Mai A. Metabolite profiling of ascidian Styela plicata using LC-MS with multivariate statistical analysis and their antitumor activity. J Enzyme Inhib Med Chem. 2017Dec;32(1):614-623. doi: 10.1080/14756366.2016.1266344. PubMed PMID: 28234548.

20. Božović M, Garzoli S, Sabatino M, Pepi F, Baldisserotto A, Andreotti E, Romagnoli C, Mai A, Manfredini S, Ragno R. Essential Oil Extraction, Chemical Analysis and Anti-Candida Activity of Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball-New Approaches. Molecules. 2017 Jan 26;22(2). pii: E203. doi: 10.3390/molecules22020203. PubMed PMID: 28134788.

21. Fulci C, Rotili D, De Luca A, Stella L, Morozzo Della Rocca B, Forgione M, Di Paolo V, Mai A, Falconi M, Quintieri L, Caccuri AM. A new nitrobenzoxadiazole-based GSTP1-1 inhibitor with a previously unheard of mechanism of action and high stability. J Enzyme Inhib Med Chem. 2017Dec;32(1):240-247. doi: 10.1080/14756366.2016.1247059. PubMed PMID: 28097896.

22. You W, Rotili D, Li TM, Kambach C, Meleshin M, Schutkowski M, Chua KF, Mai A, Steegborn C. Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules. Angew Chem Int Ed Engl. 2017 Jan 19;56(4):1007-1011. doi: 10.1002/anie.201610082. Epub 2016 Dec 19. PubMed PMID: 27990725.

23. Ourailidou ME, Lenoci A, Zwergel C, Rotili D, Mai A, Dekker FJ. Towards the development of activity-based probes for detection of lysine-specific demethylase-1 activity. Bioorg Med Chem. 2017 Feb 1;25(3):847-856. doi: 10.1016/j.bmc.2016.11.043. Epub 2016 Dec 1. PubMed PMID: 27989416; PubMed Central PMCID: PMC5292237.

24. Stunnenberg HG; International Human Epigenome Consortium, Hirst M. The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery. Cell. 2016 Nov 17;167(5):1145-1149. doi: 10.1016/j.cell.2016.11.007. Erratum in: Cell. 2016 Dec 15;167(7):1897. PubMed PMID: 27863232.

25. Panella S, Marcocci ME, Celestino I, Valente S, Zwergel C, Li Puma DD, Nencioni L, Mai A, Palamara AT, Simonetti G. MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation. Future Med Chem. 2016 Oct 14. [Epub ahead of print] PubMed PMID: 27739328.

26. Milite C, Feoli A, Viviano M, Rescigno D, Cianciulli A, Balzano AL, Mai A, Castellano S, Sbardella G. The emerging role of lysine methyltransferase SETD8 in human diseases. Clin Epigenetics. 2016 Sep 22;8:102. eCollection 2016. Review. PubMed PMID: 27688818; PubMed Central PMCID: PMC5034662.

27. Speranzini V, Rotili D, Ciossani G, Pilotto S, Marrocco B, Forgione M, Lucidi A, Forneris F, Mehdipour P, Velankar S, Mai A, Mattevi A. Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features. Sci Adv. 2016 Sep 9;2(9):e1601017. doi: 10.1126/sciadv.1601017. eCollection 2016 Sep. PubMed PMID: 27626075; PubMed Central PMCID: PMC5017823.

28. Milite C, Feoli A, Viviano M, Rescigno D, Mai A, Castellano S, Sbardella G. Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors. ChemMedChem. 2016 Aug 19;11(16):1680-5. doi: 10.1002/cmdc.201600272. Epub 2016 Jul 14. Review. PubMed PMID: 27411844.

29. Carafa V, Rotili D, Forgione M, Cuomo F, Serretiello E, Hailu GS, Jarho E, Lahtela-Kakkonen M, Mai A, Altucci L. Sirtuin functions and modulation: from chemistry to the clinic. Clin Epigenetics. 2016 May 25;8:61. doi: 10.1186/s13148-016-0224-3. eCollection 2016. Review. PubMed PMID: 27226812; PubMed Central PMCID: PMC4879741.

30. Chano T, Avnet S, Kusuzaki K, Bonuccelli G, Sonveaux P, Rotili D, Mai A, Baldini N. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells. Am J Cancer Res. 2016 Mar 15;6(4):859-75. eCollection 2016. PubMed PMID: 27186436; PubMed Central PMCID: PMC4859889.

31. Stazi G, Zwergel C, Valente S, Mai A. LSD1 inhibitors: a patent review (2010-2015). Expert Opin Ther Pat. 2016 May;26(5):565-80. doi: 10.1517/13543776.2016.1165209. Epub 2016 Mar 28. Review. PubMed PMID: 27019002.

32. Di Martile M, Desideri M, De Luca T, Gabellini C, Buglioni S, Eramo A, Sette G, Milella M, Rotili D, Mai A, Carradori S, Secci D, De Maria R, Del Bufalo D, Trisciuoglio D. Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem-like cells. Oncotarget. 2016 Mar 8;7(10):11332-48. doi: 10.18632/oncotarget.7238. PubMed PMID: 26870991; PubMed Central PMCID: PMC4905477.

33. Di Liddo R, Valente S, Taurone S, Zwergel C, Marrocco B, Turchetta R, Conconi MT, Scarpa C, Bertalot T, Schrenk S, Mai A, Artico M. Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model. Autoimmunity. 2016 Jan 20:1-11. doi: 10.3109/08916934.2015.1134510. [Epub ahead of print] PubMed PMID: 26789595.

34. van den Bosch T, Boichenko A, Leus NGJ, Ourailidou ME, Wapenaar H, Rotili D, Mai A, Imhof A, Bischoff R, Haisma HJ, Dekker FJ. The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases. Biochem Pharmacol. 2016 Feb 15;102:130-140. doi: 10.1016/j.bcp.2015.12.010. Epub 2015 Dec 21. PubMed PMID: 26718586; PubMed Central PMCID: PMC4871277.

35. Vianello P, Botrugno OA, Cappa A, Dal Zuffo R, Dessanti P, Mai A, Marrocco B, Mattevi A, Meroni G, Minucci S, Stazi G, Thaler F, Trifiró P, Valente S, Villa M, Varasi M, Mercurio C. Discovery of a Novel Inhibitor of Histone Lysine-Specific Demethylase 1A (KDM1A/LSD1) as Orally Active Antitumor Agent. J Med Chem. 2016 Feb 25;59(4):1501-17. doi: 10.1021/acs.jmedchem.5b01209. Epub 2016 Jan 7. PubMed PMID: 26702542.

36. Valente S, Mellini P, Spallotta F, Carafa V, Nebbioso A, Polletta L, Carnevale I, Saladini S, Trisciuoglio D, Gabellini C, Tardugno M, Zwergel C, Cencioni C, Atlante S, Moniot S, Steegborn C, Budriesi R, Tafani M, Del Bufalo D, Altucci L, Gaetano C, Mai A. 1,4-Dihydropyridines Active on the SIRT1/AMPK Pathway Ameliorate Skin Repair and Mitochondrial Function and Exhibit Inhibition of Proliferation in Cancer Cells. J Med Chem. 2016 Feb 25;59(4):1471-91. doi: 10.1021/acs.jmedchem.5b01117. Epub 2016 Jan 5. PubMed PMID: 26689352.

37. Wapenaar H, van der Wouden PE, Groves MR, Rotili D, Mai A, Dekker FJ. Enzyme kinetics and inhibition of histone acetyltransferase KAT8. Eur J Med Chem. 2015 Nov 13;105:289-96. doi: 10.1016/j.ejmech.2015.10.016. Epub 2015 Oct 22. PubMed PMID: 26505788; PubMed Central PMCID: PMC4871228.

38. Wang Q, Rosa BA, Nare B, Powell K, Valente S, Rotili D, Mai A, Marshall GR, Mitreva M. Targeting Lysine Deacetylases (KDACs) in Parasites. PLoS Negl Trop Dis. 2015 Sep 24;9(9):e0004026. doi: 10.1371/journal.pntd.0004026. eCollection 2015. PubMed PMID: 26402733; PubMed Central PMCID: PMC4581690.

39. Piano V, Benjamin DI, Valente S, Nenci S, Marrocco B, Mai A, Aliverti A, Nomura DK, Mattevi A. Discovery of Inhibitors for the Ether Lipid-Generating Enzyme AGPS as Anti-Cancer Agents. ACS Chem Biol. 2015 Nov 20;10(11):2589-97. doi: 10.1021/acschembio.5b00466. Epub 2015 Sep 4. PubMed PMID: 26322624; PubMed Central PMCID: PMC4703096.

40. Zwergel C, Valente S, Mai A. DNA Methyltransferases Inhibitors from Natural Sources. Curr Top Med Chem. 2016;16(7):680-96. Review. PubMed PMID: 26303417.

41. Di Pompo G, Salerno M, Rotili D, Valente S, Zwergel C, Avnet S, Lattanzi G, Baldini N, Mai A. Novel histone deacetylase inhibitors induce growth arrest, apoptosis, and differentiation in sarcoma cancer stem cells. J Med Chem. 2015 May 14;58(9):4073-9. doi: 10.1021/acs.jmedchem.5b00126. Epub 2015 Apr 30. PubMed PMID: 25905694.

42. Zwergel C, Valente S, Jacob C, Mai A. Emerging approaches for histone deacetylase inhibitor drug discovery. Expert Opin Drug Discov. 2015 Jun;10(6):599-613. doi: 10.1517/17460441.2015.1038236. Epub 2015 Apr 20. Review. PubMed PMID: 25895649.

43. Graziani G, Artuso S, De Luca A, Muzi A, Rotili D, Scimeca M, Atzori MG, Ceci C, Mai A, Leonetti C, Levati L, Bonanno E, Tentori L, Caccuri AM. A new water soluble MAPK activator exerts antitumor activity in melanoma cells resistant to the BRAF inhibitor vemurafenib. Biochem Pharmacol. 2015 May 1;95(1):16-27. doi: 10.1016/j.bcp.2015.03.004. Epub 2015 Mar 17. PubMed PMID: 25795251.

44. Valente S, Rodriguez V, Mercurio C, Vianello P, Saponara B, Cirilli R, Ciossani G, Labella D, Marrocco B, Monaldi D, Ruoppolo G, Tilset M, Botrugno OA, Dessanti P, Minucci S, Mattevi A, Varasi M, Mai A. Pure enantiomers of benzoylamino-tranylcypromine: LSD1 inhibition, gene modulation in human leukemia cells and effects on clonogenic potential of murine promyelocytic blasts. Eur J Med Chem. 2015 Apr 13;94:163-74. doi: 10.1016/j.ejmech.2015.02.060. Epub 2015 Mar 3. PubMed PMID: 25768700.

45. Pilotto S, Speranzini V, Tortorici M, Durand D, Fish A, Valente S, Forneris F, Mai A, Sixma TK, Vachette P, Mattevi A. Interplay among nucleosomal DNA, histone tails, and corepressor CoREST underlies LSD1-mediated H3 demethylation. Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2752-7. doi: 10.1073/pnas.1419468112. Epub 2015 Feb 17. PubMed PMID: 25730864; PubMed Central PMCID: PMC4352788.

46. Milite C, Feoli A, Sasaki K, La Pietra V, Balzano AL, Marinelli L, Mai A, Novellino E, Castellano S, Tosco A, Sbardella G. A novel cell-permeable, selective, and noncompetitive inhibitor of KAT3 histone acetyltransferases from a combined molecular pruning/classical isosterism approach. J Med Chem. 2015 Mar 26;58(6):2779-98. doi: 10.1021/jm5019687. Epub 2015 Mar 10. PubMed PMID:25730130.

47. Polletta L, Vernucci E, Carnevale I, Arcangeli T, Rotili D, Palmerio S, Steegborn C, Nowak T, Schutkowski M, Pellegrini L, Sansone L, Villanova L, Runci A, Pucci B, Morgante E, Fini M, Mai A, Russo MA, Tafani M. SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy. 2015;11(2):253-70. doi: 10.1080/15548627.2015.1009778. PubMed PMID: 25700560; PubMed Central PMCID: PMC4502726.

48. Valente S, Rodriguez V, Mercurio C, Vianello P, Saponara B, Cirilli R, Ciossani G, Labella D, Marrocco B, Ruoppolo G, Botrugno OA, Dessanti P, Minucci S, Mattevi A, Varasi M, Mai A. Pure Diastereomers of a Tranylcypromine-Based LSD1 Inhibitor: Enzyme Selectivity and In-Cell Studies. ACS Med Chem Lett. 2014 Dec 8;6(2):173-7. doi: 10.1021/ml500424z. eCollection 2015 Feb 12. PubMed PMID: 25699146; PubMed Central PMCID: PMC4329595.

49. De Luca A, Rotili D, Carpanese D, Lenoci A, Calderan L, Scimeca M, Mai A, Bonanno E, Rosato A, Geroni C, Quintieri L, Caccuri AM. A novel orally active water-soluble inhibitor of human glutathione transferase exerts a potent andselective antitumor activity against human melanoma xenografts. Oncotarget. 2015 Feb 28;6(6):4126-43. PubMed PMID: 25595904; PubMed Central PMCID: PMC4414177.

50. Cencioni C, Spallotta F, Mai A, Martelli F, Farsetti A, Zeiher AM, Gaetano C. Sirtuin function in aging heart and vessels. J Mol Cell Cardiol. 2015 Jun;83:55-61. doi: 10.1016/j.yjmcc.2014.12.023. Epub 2015 Jan 9. Review. PubMed PMID: 25579854.

51. Gros C, Fleury L, Nahoum V, Faux C, Valente S, Labella D, Cantagrel F, Rilova E, Bouhlel MA, David-Cordonnier MH, Dufau I, Ausseil F, Mai A, Mourey L, Lacroix L, Arimondo PB. New insights on the mechanism of quinoline-based DNA Methyltransferase inhibitors. J Biol Chem. 2015 Mar 6;290(10):6293-302. doi: 10.1074/jbc.M114.594671. Epub 2014 Dec 18. PubMed PMID: 25525263; PubMed Central PMCID: PMC4358266.

52. Rotili D, De Luca A, Tarantino D, Pezzola S, Forgione M, Morozzo Della Rocca B, Falconi M, Mai A, Caccuri AM. Synthesis and structure--activity relationship of new cytotoxic agents targeting human glutathione-S-transferases. Eur J Med Chem. 2015 Jan 7;89:156-71. doi: 10.1016/j.ejmech.2014.10.033. Epub 2014 Oct 13. PubMed PMID: 25462236.

53. Mellini P, Valente S, Mai A. Sirtuin modulators: an updated patent review (2012 - 2014). Expert Opin Ther Pat. 2015 Jan;25(1):5-15. doi: 10.1517/13543776.2014.982532. Epub 2014 Nov 29. Review. PubMed PMID: 25435179.

54. Castellano S, Milite C, Feoli A, Viviano M, Mai A, Novellino E, Tosco A, Sbardella G. Identification of structural features of 2-alkylidene-1,3-dicarbonyl derivatives that induce inhibition and/or activation of histone acetyltransferases KAT3B/p300 and KAT2B/PCAF. ChemMedChem. 2015 Jan;10(1):144-57.doi: 10.1002/cmdc.201402371. Epub 2014 Oct 21. PubMed PMID: 25333655.