Conjugates of Cryptophycin and RGD or isoDGR Peptidomimetics for Targeted Drug Delivery.
Borbély A, Figueras E, Martins A, Bodero L, Raposo Moreira Dias A, López Rivas P, Pina A, Arosio D, Gallinari P, Frese M, Steinkühler C, Gennari C, Piarulli U, Sewald N.
ChemistryOpen. 8: 737-742 (2019)
Octreotide Conjugates for Tumor Targeting and Imaging.
Figueras E, Martins A, Borbély A, Le Joncour V, Cordella P, Perego R, Modena D, Pagani P, Esposito S, Auciello G, Frese M, Gallinari P, Laakkonen P, Steinkühler C, Sewald N.
Pharmaceutics. 11(5). pii: E220 (2019)
Synthesis and Biological Evaluation of RGD⁻Cryptophycin Conjugates for Targeted Drug Delivery.
Borbély A, Figueras E, Martins A, Esposito S, Auciello G, Monteagudo E, Di Marco A, Summa V, Cordella P, Perego R, Kemker I, Frese M, Gallinari P, Steinkühler C, Sewald N.
Pharmaceutics. 11(4) pii: E151 (2019)
Synthesis and Biological Evaluation of RGD and isoDGR-Monomethyl Auristatin Conjugates Targeting Integrin αV β3.
Raposo Moreira Dias A, Bodero L, Martins A, Arosio D, Gazzola S, Belvisi L, Pignataro L, Steinkühler C, Dal Corso A, Gennari C, Piarulli U.
ChemMedChem. 14(9):938-942 (2019)
In Vivo Antitumor Activity of a Novel Acetazolamide-Cryptophycin Conjugate for the Treatment of Renal Cell Carcinomas.
Cazzamalli S, Figueras E, Pethő L, Borbély A, Steinkühler C, Neri D, Sewald N.
ACS Omega. 3 (11):14726-14731 (2018)
MK-4101 – a potent inhibitor of the hedgehog pathway – is highly active against medulloblastoma and basal cell carcinoma.
Filocamo G, Brunetti M, Colaceci F, Sasso R, Tanori M, Pasquali E, Alfonsi R, Mancuso M, Saran A, Lahm A, Di Marcotullio L, Steinkuhler C, Pazzaglia S.
Molecular Cancer Therapeutics 2016. Published Online First March 9, 2016; doi: 10.1158/1535-7163.MCT-15-0371
Blocking the association of HDAC4 with MAP1S accelerates autophagy clearance of mutant Huntingtin.
Yue F, Li W, Zou J, Chen Q, Xu G, Huang H, Xu Z, Zhang S, Gallinari P, Wang F, McKeehan WL, Liu L.
Aging (Albany NY). 7: 839-53 (2015)
Critical role of zinc finger protein 521 in the control of growth, clonogenicity and tumorigenic potential of medulloblastoma cells.
Spina R, Filocamo G, Iaccino E, Scicchitano S, Lupia M, Chiarella E, Mega T, Bernaudo F, Pelaggi D, Mesuraca M, Pazzaglia S, Semenkow S, Bar EE, Kool M, Pfister S, Bond HM, Eberhart CG, Steinkühler C, Morrone G.
Oncotarget. 2013 Aug;4(8):1280-92.
Skin equivalents: a tool for the discovery and validation of pharmacodynamic biomarkers.
Paolini C, Orecchia A, Failla CM, Gallinari P, Zambruno G, Steinkühler C.
Cancer Invest. 2013 Jan;31(1):60-6. doi: 10.3109/07357907.2012.749269.
Discovery of salermide-related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells.
Rotili D, Tarantino D, Nebbioso A, Paolini C, Huidobro C, Lara E, Mellini P, Lenoci A, Pezzi R, Botta G, Lahtela-Kakkonen M, Poso A, Steinkühler C, Gallinari P, De Maria R, Fraga M, Esteller M, Altucci L, Mai A.
J Med Chem. 2012 Dec 27;55(24):10937-47. doi: 10.1021/jm3011614. Epub 2012 Dec 12.
Benzodeazaoxaflavins as sirtuin inhibitors with antiproliferative properties in cancer stem cells.
Rotili D, Tarantino D, Carafa V, Paolini C, Schemies J, Jung M, Botta G, Di Maro S, Novellino E, Steinkühler C, De Maria R, Gallinari P, Altucci L, Mai A.
J Med Chem. 2012 Sep 27;55(18):8193-7. Epub 2012 Sep 7.
Antibody-drug conjugates in tumor therapy.
Sammet B, Steinkühler C, Sewald N.
Pharm Pat Anal. 2012 Mar;1(1):65-73. doi: 10.4155/ppa.12.4. Review.
Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors.
Ontoria JM, Bufi LL, Torrisi C, Bresciani A, Giomini C, Rowley M, Serafini S, Bin H, Hao W, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5274-82. doi: 10.1016/j.bmcl.2011.07.031. Epub 2011 Jul 14.
N-(2-alkylaminoethyl)-4-(1,2,4-oxadiazol-5-yl)piperazine-1-carboxamides as highly potent smoothened antagonists.
Muraglia E, Ontoria JM, Branca D, Dessole G, Bresciani A, Fonsi M, Giuliano C, Llauger Bufi L, Monteagudo E, Palumbi MC, Torrisi C, Rowley M, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5283-8. doi: 10.1016/j.bmcl.2011.07.030. Epub 2011 Jul 14.
Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimid azo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, part 1.
Malancona S, Altamura S, Filocamo G, Kinzel O, Hernando JI, Rowley M, Scarpelli R, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2011 Aug 1;21(15):4422-8. doi: 10.1016/j.bmcl.2011.06.024. Epub 2011 Jun 16.
Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, part 2.
Kinzel O, Alfieri A, Altamura S, Brunetti M, Bufali S, Colaceci F, Ferrigno F, Filocamo G, Fonsi M, Gallinari P, Malancona S, Hernando JI, Monteagudo E, Orsale MV, Palumbi MC, Pucci V, Rowley M, Sasso R, Scarpelli R, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2011 Aug 1;21(15):4429-35. doi: 10.1016/j.bmcl.2011.06.023. Epub 2011 Jun 16.
Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation.
Canettieri G, Di Marcotullio L, Greco A, Coni S, Antonucci L, Infante P, Pietrosanti L, De Smaele E, Ferretti E, Miele E, Pelloni M, De Simone G, Pedone EM, Gallinari P, Giorgi A, Steinkühler C, Vitagliano L, Pedone C, Schinin ME, Screpanti I, Gulino A.
Nat Cell Biol. 2010 Feb;12(2):132-42.
Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy.
Ontoria JM, Altamura S, Di Marco A, Ferrigno F, Laufer R, Muraglia E, Palumbi MC, Rowley M, Scarpelli R, Schultz-Fademrecht C, Serafini S, Steinkühler C, Jones P.
J Med Chem. 2009 Nov 12;52(21):6782-9.
Loss of histone deacetylase 4 causes segregation defects during mitosis of p53-deficient human tumor cells.
Cadot B, Brunetti M, Coppari S, Fedeli S, de Rinaldis E, Dello Russo C, Gallinari P, De Francesco R, Steinkühler C, Filocamo G.
Cancer Res. 2009 Aug 1;69(15):6074-82.
Smoothened Antagonists: A Promising new Class of Antitumor Agents.
Gallinari P, Filocamo G, Jones P, Pazzaglia S, Steinkühler C.
Expert Opinion on Drug Discovery 2009 4(5), 525-544
Discovery of N-[(1-aryl-1H-indazol-5-yl)methyl]amides derivatives as smoothened antagonists for inhibition of the hedgehog pathway.
Dessole G, Branca D, Ferrigno F, Kinzel O, Muraglia E, Palumbi MC, Rowley M, Serafini S, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2009 Aug 1;19(15):4191-5.
Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties.
Kinzel O, Llauger-Bufi L, Pescatore G, Rowley M, Schultz-Fademrecht C, Monteagudo E, Fonsi M, Gonzalez Paz O, Fiore F, Steinkühler C, Jones P.
J Med Chem. 2009 Jun 11;52(11):3453-6.
Histone deacetylase inhibitors with a primary amide zinc binding group display antitumor activity in xenograft model.
Attenni B, Ontoria JM, Cruz JC, Rowley M, Schultz-Fademrecht C, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2009 Jun 1;19(11):3081-4.
HDAC2 blockade by nitric oxide and histone deacetylase inhibitors reveals a common target in Duchenne muscular dystrophy treatment.
Colussi C, Mozzetta C, Gurtner A, Illi B, Rosati J, Straino S, Ragone G, Pescatori M, Zaccagnini G, Antonini A, Minetti G, Martelli F, Piaggio G, Gallinari P, Steinkuhler C, Clementi E, Dell’Aversana C, Altucci L, Mai A, Capogrossi MC, Puri PL, Gaetano C.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19183-7.
Studies of the metabolic stability in cells of 5-(trifluoroacetyl)thiophene-2-carboxamides and identification of more stable class II histone deacetylase (HDAC) inhibitors.
Scarpelli R, Di Marco A, Ferrigno F, Laufer R, Marcucci I, Muraglia E, Ontoria JM, Rowley M, Serafini S, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6078-82.
2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors.
Muraglia E, Altamura S, Branca D, Cecchetti O, Ferrigno F, Orsale MV, Palumbi MC, Rowley M, Scarpelli R, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6083-7.
Optimization of a series of potent and selective ketone histone deacetylase inhibitors.
Pescatore G, Kinzel O, Attenni B, Cecchetti O, Fiore F, Fonsi M, Rowley M, Schultz-Fademrecht C, Serafini S, Steinkühler C, Jones P.
Bioorg Med Chem Lett. 2008 Oct 15;18(20):5528-32.
Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure.
Gallo P, Latronico MV, Gallo P, Grimaldi S, Borgia F, Todaro M, Jones P, Gallinari P, De Francesco R, Ciliberto G, Steinkühler C, Esposito G, Condorelli G.
Cardiovasc Res. 2008 Dec 1;80(3):416-24.
Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.
Bottomley MJ, Lo Surdo P, Di Giovine P, Cirillo A, Scarpelli R, Ferrigno F, Jones P, Neddermann P, De Francesco R, Steinkühler C, Gallinari P, Carfí A.
J Biol Chem. 2008 Sep 26;283(39):26694-704.
2-Trifluoroacetylthiophenes, a novel series of potent and selective class II histone deacetylase inhibitors.
Jones P, Bottomley MJ, Carfí A, Cecchetti O, Ferrigno F, Lo Surdo P, Ontoria JM, Rowley M, Scarpelli R, Schultz-Fademrecht C, Steinkühler C.
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3456-61.
Development and optimization of a binding assay for histone deacetylase 4 using surface plasmon resonance.
Mattu M, Di Giovine P, Steinkuhler C, De Francesco R, Altamura S, Cecchetti O, Carfì A, Barbato G.
Anal Biochem. 2008 Jun 15;377(2):267-9.
A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo.
Jones P, Altamura S, De Francesco R, Paz OG, Kinzel O, Mesiti G, Monteagudo E, Pescatore G, Rowley M, Verdirame M, Steinkühler C.
J Med Chem. 2008 Apr 24;51(8):2350-3.
From natural products to small molecule ketone histone deacetylase inhibitors: development of new class specific agents.
Jones P, Steinkühler C.
Curr Pharm Des. 2008;14(6):545-61. Review.
Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases.
Jones P, Altamura S, De Francesco R, Gallinari P, Lahm A, Neddermann P, Rowley M, Serafini S, Steinkühler C.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):1814-9
PP2A regulates HDAC4 nuclear import.
Paroni G, Cernotta N, Dello Russo C, Gallinari P, Pallaoro M, Foti C, Talamo F, Orsatti L, Steinkühler C, Brancolini C.
Mol Biol Cell. 2008 Feb;19(2):655-67.
Nitric oxide modulates chromatin folding in human endothelial cells via protein phosphatase 2A activation and class II histone deacetylases nuclear shuttling.
Illi B, Dello Russo C, Colussi C, Rosati J, Pallaoro M, Spallotta F, Rotili D, Valente S, Ragone G, Martelli F, Biglioli P, Steinkuhler C, Gallinari P, Mai A, Capogrossi MC, Gaetano C
Circ Res. 2008 Jan 4;102(1):51-8.
Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases.
Lahm A, Paolini C, Pallaoro M, Nardi MC, Jones P, Neddermann P, Sambucini S, Bottomley MJ, Lo Surdo P, Carfí A, Koch U, De Francesco R, Steinkühler C, Gallinari P.
Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17335-40.
Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex.
Vannini A, Volpari C, Gallinari P, Jones P, Mattu M, Carfí A, De Francesco R, Steinkühler C, Di Marco S.
EMBO Rep. 2007 Sep;8(9):879-84.
HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics.
Gallinari P, Di Marco S, Jones P, Pallaoro M, Steinkühler C.
Cell Res. 2007 Mar;17(3):195-211.
A series of novel, potent, and selective histone deacetylase inhibitors.
Jones P, Altamura S, Chakravarty PK, Cecchetti O, De Francesco R, Gallinari P, Ingenito R, Meinke PT, Petrocchi A, Rowley M, Scarpelli R, Serafini S., Steinkühler C.
Bioorg Med Chem Lett. 2006 Dec 1;16(23):5948-52.
Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors.
Minetti GC, Colussi C, Adami R, Serra C, Mozzetta C, Parente V, Fortuni S, Straino S, Sampaolesi M, Di Padova M, Illi B, Gallinari P, Steinkühler C, Capogrossi MC, Sartorelli V, Bottinelli R, Gaetano C, Puri PL.
Nat Med. 2006 Oct;12(10):1147-50.
Dissecting the biological functions of Drosophila histone deacetylases by RNA interference and transcriptional profiling.
Foglietti C, Filocamo G, Cundari E, De Rinaldis E, Lahm A, Cortese R, Steinkühler C.
J Biol Chem. 2006 Jun 30;281(26):17968-76.
The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease.
Ontoria JM, Di Marco S, Conte I, Di Francesco ME, Gardelli C, Koch U, Matassa VG, Poma M, Steinkühler C, Volpari C, Harper S.
J Med Chem. 2004 Dec 16;47(26):6443-6.
Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor.
Vannini A, Volpari C, Filocamo G, Casavola EC, Brunetti M, Renzoni D, Chakravarty P, Paolini C, De Francesco R, Gallinari P, Steinkühler C, Di Marco S.
Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15064-9
Patents:
WO2016146638: Cryptophycin-Based Antibody-Drug Conjugates with Novel Self-Immolative Linkers.
Steinkühler C., Gallinari P., Osswald B., Sewald N., Ritzefeld M., Frese M.
WO2019034427A1: MONOCLONAL ANTIBODY ANTI-FGFR4.
Gallinari P, Paolini C, Filocamo G, Brunetti M, Lahm A, Grunert F, Thompson J, Ricci-Vitiani L, Biffoni M