Our Science

Combining experience with innovation across the drug discovery process

Our Approach
Our fully integrated scientific team translates expertise in cellular and molecular biology, medicinal, computational and analytical chemistry into the discovery and development of innovative therapies.
We have a broad portfolio of drug discovery projects based on in-house research that are unlocking the potential of novel therapeutic targets, including orphan nuclear receptors.

Publications

Liscio P, Rosatelli E, Cianci M, Carotti A, Giacchè N, De Franco F, Raffaelli N, Pellicciari R.

Discovery, Properties and Structural Biology Appraisal of TES-1025 as the First In Class Potent and Selective ACMSD Inhibitor.

XXVIII EFMC-ISMC 2024, Rome, Italy - September 1-5, 2024

Manni G, Gargaro M, Ricciuti D, Fontana S, Padiglioni E, Cipolloni M, Mazza T, Rosati J, di Veroli A, Mencarelli G, Pieroni B, Silva Barcelos EC, Scalisi G, Sarnari F, di Michele A, Pascucci L, de Franco F, Zelante T, Antognelli C, Cruciani G, Talesa VN, Romani R, Fallarino F.

Amniotic fluid stem cell-derived extracellular vesicles educate type 2 conventional dendritic cells to rescue autoimmune disorders in a multiple sclerosis mouse model.

J Extracell Vesicles. 2024 Jun;13(6):e12446. doi: 10.1002/jev2.12446.

La Spada G, Miniero DV, Rullo M, Cipolloni M, Delre P, Colliva C, Colella M, Leonetti F, Liuzzi GM, Mangiatordi GF, Giacchè N, Pisani L.

Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: AChE/BChE selectivity switch and drug-like characterization.

Eur J Med Chem. 2024 Aug 5;274:116511. doi: 10.1016/j.ejmech.2024.116511.

Bartolini D, Stabile AM, Migni A, Gurrado F, Lioci G, De Franco F, Mandarano M, Svegliati-Baroni G, Di Cristina M, Bellezza G, Rende M, Galli F.

Subcellular distribution and Nrf2/Keap1-interacting properties of Glutathione S-transferase P in hepatocellular carcinoma.

Arch Biochem Biophys. 2024 Jul;757:110043. doi: 10.1016/j.abb.2024.110043.

Ceccarelli G, Goracci L, Carotti A, Paccoia F, Passeri D, Cipolloni M, Di Bona S, Cruciani G, Pellicciari R, Gioiello A.

Discovery and Structure-Activity Relationships of Novel ssDAF-12 Receptor Modulators.

J Med Chem. 2024 Mar 14;67(5):4150-4169. doi: 10.1021/acs.jmedchem.3c02421.

Gioiello A, Rosatelli E, Cerra B.

Patented Farnesoid X receptor modulators: a review (2019 - present).

Expert Opin Ther Pat. 2024 Feb 26:1-18. doi: 10.1080/13543776.2024.2314296.

Myers SH, Poppi L, Rinaldi F, Veronesi M, Ciamarone A, Previtali V, Bagnolini G, Schipani F, Ortega MartĂ­nez JA, Girotto S, Di Stefano G, Farabegoli F, Walsh N, De Franco F, Roberti M, Cavalli A.

An 19F NMR fragment-based approach for the discovery and development of BRCA2-RAD51 inhibitors to pursuit synthetic lethality in combination with PARP inhibition in pancreatic cancer.

Eur J Med Chem. 2023 Dec 31;265:116114. doi: 10.1016/j.ejmech.2023.116114.

Poonsiri T, Dell'Accantera D, Loconte V, Casnati A, Cervoni L, Arcovito A, Benini S, Ferrari A, Cipolloni M, Cacioni E, De Franco F, Giacchè N, Rinaldo S, Folli C, Sansone F, Berni R, Cianci M.

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity.

Int J Mol Sci. 2023 Dec 29;25(1):479. doi: 10.3390/ijms25010479.

Rosatelli E, Carotti A, Cerra B, De Franco F, Passeri D, Pellicciari R, Gioiello A.

Chemical exploration of TGR5 functional hot-spots: Synthesis and structure-activity relationships of C7- and C23-Substituted cholic acid derivatives.

Eur J Med Chem. 2023 Dec 5:261:115851. doi: 10.1016/j.ejmech.2023.115851.

Pérez-Gordillo FL, Serrano-Morillas N, Acosta-García LM, Aranda MT, Passeri D, Pellicciari R, Pérez de Vega MJ, González-Muñiz R, Alvarez de la Rosa D, Martín-Martínez M.

Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists.

Int J Mol Sci. 2023 Jan 26;24(3):2439. doi: 10.3390/ijms24032439.

Di Bello E, Sian V, Bontempi G, Zwergel C, Fioravanti R, Noce B, Castiello C, Tomassi S, Corinti D, Passeri D, Pellicciari R, Mercurio C, Varasi M, Altucci L, Tripodi M, Strippoli R, Nebbioso A, Valente S, Mai A.

Novel pyridine-containing histone deacetylase inhibitors strongly arrest proliferation, induce apoptosis and modulate miRNAs in cancer cells.

Eur J Med Chem. 2022 Dec 15;247:115022. doi: 10.1016/j.ejmech.2022.115022.

Marzano M, Fosso B, Colliva C, Notario E, Passeri D, Intranuovo M, Gioiello A, Adorini L, Pesole G, Pellicciari R, Moschetta A, Gadaleta RM.

Farnesoid X receptor activation by the novel agonist TC-100 (3α, 7α, 11β-Trihydroxy-6α-ethyl-5β-cholan-24-oic Acid) preserves the intestinal barrier integrity and promotes intestinal microbial reshaping in a mouse model of obstructed bile acid flow.

Biomed Pharmacother. 2022 Sep;153:113380. doi: 10.1016/j.biopha.2022.113380.

Cerra B, Venturoni F, Souma M, Ceccarelli G, Lozza AM, Passeri D, De Franco F, Baxendale IR, Pellicciari R, Macchiarulo A, Gioiello A.

Development of 3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-sulfate sodium salt (INT-767): Process optimization, synthesis and characterization of metabolites.

Eur J Med Chem. 2022 Aug 20;242:114652. doi: 10.1016/j.ejmech.2022.114652.

Bagnolini G, Balboni B, Schipani F, Gioia D, Veronesi M, De Franco F, Kaya C, Jumde RP, Ortega JA, Girotto S, Hirsch AKH, Roberti M, Cavalli A.

Identification of RAD51-BRCA2 Inhibitors Using N-Acylhydrazone-Based Dynamic Combinatorial Chemistry.

ACS Med Chem Lett. 2022 Jul 28;13(8):1262-1269. doi: 10.1021/acsmedchemlett.2c00063.

Gargaro M, Scalisi G, Manni G, Briseño CG, Bagadia P, Durai V, Theisen DJ, Kim S, Castelli M, Xu CA, Zu Hörste GM, Servillo G, Della Fazia MA, Mencarelli G, Ricciuti D, Padiglioni E, Giacchè N, Colliva C, Pellicciari R, Calvitti M, Zelante T, Fuchs D, Orabona C, Boon L, Bessede A, Colonna M, Puccetti P, Murphy TL, Murphy KM, Fallarino F.

Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication.

Immunity. 2022 Jun 14;55(6):1032-1050.e14. doi: 10.1016/j.immuni.2022.05.013.

Cianci M, Giacchè N, Cialabrini L, Carotti A, Liscio P, Rosatelli E, De Franco F, Gasparrini M, Robertson J, Amici A, Raffaelli N, Pellicciari R.

Structural Basis of Human Dimeric α-Amino-β-Carboxymuconate-ε-Semialdehyde Decarboxylase Inhibition With TES-1025.

Front Mol Biosci. 2022 Apr 7;9:834700. doi: 10.3389/fmolb.2022.834700.

Rullo M, Cipolloni M, Catto M, Colliva C, Miniero DV, Latronico T, de Candia M, Benicchi T, Linusson A, Giacchè N, Altomare CD, Pisani L.

Probing Fluorinated Motifs onto Dual AChE-MAO B Inhibitors: Rational Design, Synthesis, Biological Evaluation, and Early-ADME Studies.

J Med Chem. 2022 Mar 10;65(5):3962-3977. doi: 10.1021/acs.jmedchem.1c01784.

Nowak RP, Tumber A, Hendrix E, Ansari MSZ, Sabatino M, Antonini L, Andrijes R, Salah E, Mautone N, Pellegrini FR, Simelis K, Kawamura A, Johansson C, Passeri D, Pellicciari R, Ciogli A, Del Bufalo D, Ragno R, Coleman ML, Trisciuoglio D, Mai A, Oppermann U, Schofield CJ, Rotili D.

First-in-Class Inhibitors of the Ribosomal Oxygenase MINA53.

J Med Chem. 2021 Dec 9;64(23):17031-17050. doi: 10.1021/acs.jmedchem.1c00605.

Ijssennagger N, van Rooijen KS, MagnĂşsdĂłttir S, Ramos Pittol JM, Willemsen ECL, de Zoete MR, Baars MJD, Stege PB, Colliva C, Pellicciari R, Youssef SA, de Bruin A, Vercoulen Y, Kuipers F, van Mil SWC.

Ablation of liver Fxr results in an increased colonic mucus barrier in mice.

JHEP Rep. 2021 Aug 4;3(5):100344. doi: 10.1016/j.jhepr.2021.100344.

Mancino V, Ceccarelli G, Carotti A, Goracci L, Sardella R, Passeri D, Pellicciari R, Gioiello A.

Synthesis and biological activity of cyclopropyl Δ7-dafachronic acids as DAF-12 receptor ligands.

Org Biomol Chem. 2021 Jun 28;19(24):5403-5412. doi: 10.1039/d1ob00912e.

Perino A, Velázquez-Villegas LA, Bresciani N, Sun Y, Huang Q, Fénelon VS, Castellanos-Jankiewicz A, Zizzari P, Bruschetta G, Jin S, Baleisyte A, Gioiello A, Pellicciari R, Ivanisevic J, Schneider BL, Diano S, Cota D, Schoonjans K.

Central anorexigenic actions of bile acids are mediated by TGR5.

Nat Metab. 2021 May;3(5):595-603. doi: 10.1038/s42255-021-00398-4.

Manrique-Caballero CL, Kellum JA, Gomez H, De Franco F, Giacche N, Pellicciari R.

Innovations and emerging therapies to combat renal cell damage: NAD+ as a drug target.

Antioxid Redox Signal. 2021 Dec 10;35(17):1449-1466. doi: 10.1089/ars.2020.8066.

Ferri M, Alunno M, Greco FA, Mammoli A, Saluti G, Carotti A, Sardella R, Macchiarulo A, Camaioni E, Liscio P.

Fragment based drug design and diversity-oriented synthesis of carboxylic acid isosteres.

Bioorg Med Chem. 2020 Nov 15;28(22):115731. doi: 10.1016/j.bmc.2020.115731.

Dvorak Z, Klapholz M, Burris TP, Willing BP, Gioiello A, Pellicciari R, Galli F, March J, O'Keefe SJ, Sartor RB, Kim CH, Levy M, Mani S.

Weak Microbial Metabolites: a Treasure Trove for Using Biomimicry to Discover and Optimize Drugs.

Mol Pharmacol. 2020 Oct;98(4):343-349. doi: 10.1124/molpharm.120.000035.

Sorrentino G, Perino A, Yildiz E, El Alam G, Bou Sleiman M, Gioiello A, Pellicciari R, Schoonjans K.

Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration.

Gastroenterology. 2020 Sep;159(3):956-968.e8.

Tomassi S, Pfahler J, Mautone N, Rovere A, Esposito C, Passeri D, Pellicciari R, Novellino E, Pannek M, Steegborn C, Paiardini A, Mai A, Rotili D.

From PARP1 to TNKS2 Inhibition: A Structure-Based Approach.

ACS Med Chem Lett. 2020 Feb 3;11(5):862-868.

Bartolini D, De Franco F, Torquato P, Marinelli R, Cerra B, Ronchetti R, Schon A, Fallarino F, De Luca A, Bellezza G, Ferri I, Sidoni A, Walton WG, Pellock SJ, Redinbo MR, Mani S, Pellicciari R, Gioiello A, Galli F.

Garcinoic Acid Is a Natural and Selective Agonist of Pregnane X Receptor.

J Med Chem. 2020 Apr 9;63(7):3701-3712.

Bagnolini G, Milano D, Manerba M, Schipani F, Ortega JA, Gioia D, Falchi F, Balboni A, Farabegoli F, De Franco F, Robertson J, Pellicciari R, Pallavicini I, Peri S, Minucci S, Girotto S, Di Stefano G, Roberti M, Cavalli A.

Synthetic Lethality in Pancreatic Cancer: Discovery of a New RAD51-BRCA2 Small Molecule Disruptor That Inhibits Homologous Recombination and Synergizes with Olaparib.

J Med Chem. 2020 Mar 12;63(5):2588-2619.

Passeri D, Carotti A, Pittol JMR, Ciaccioli G, Pellicciari R, van Mil SWC, Gioiello A.

Dissecting the allosteric FXR modulation: a chemical biology approach using guggulsterone as a chemical tool.

Medchemcomm. 2019 Jun 24;10(8):1412-1419.

Cerra B, Carotti A, Passeri D, Sardella R, Moroni G, Di Michele A, Macchiarulo A, Pellicciari R, Gioiello A.

Exploiting Chemical Toolboxes for the Expedited Generation of Tetracyclic Quinolines as a Novel Class of PXR Agonists.

ACS Med Chem Lett. 2018 Dec 27;10(4):677-681.

Roberti M, Schipani F, Bagnolini G, Milano D, Giacomini E, Falchi F, Balboni A, Manerba M, Farabegoli F, De Franco F, Robertson J, Minucci S, Pallavicini I, Di Stefano G, Girotto S, Pellicciari R, Cavalli A.

Rad51/BRCA2 disruptors inhibit homologous recombination and synergize with olaparib in pancreatic cancer cells.

Eur J Med Chem. 2019 Mar 1;165:80-92.

Katsyuba E, Mottis A, Zietak M, De Franco F, van der Velpen V, Gariani K, Ryu D, Cialabrini L, Matilainen O, Liscio P, Giacchè N, Stokar-Regenscheit N, Legouis D, de Seigneux S, Ivanisevic J, Raffaelli N, Schoonjans K, Pellicciari R & Auwerx J.

De novo NAD+ synthesis enhances mitochondrial function and improves health.

Nature. 2018 Nov;563(7731):354-359.

Massafra V, Pellicciari R, Gioiello A, van Mil SWC.

Progress and challenges of selective Farnesoid X Receptor modulation

Pharmacol Ther. 2018 Nov;191:162-177. doi: 10.1016/j.pharmthera.2018.06.009.

Pellicciari R, Liscio P, Giacchè N, De Franco F, Carotti A, Robertson J, Cialabrini L, Katsyuba E, Raffaelli N, Auwerx J.

α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis.

J Med Chem. 2018 Feb 8;61(3):745-759.

Mostarda S, Passeri D, Carotti A, Cerra B, Colliva C, Benicchi T, Macchiarulo A, Pellicciari R, Gioiello A.

Synthesis, physicochemical properties, and biological activity of bile acids 3-glucuronides: Novel insights into bile acid signalling and detoxification.

Eur J Med Chem. 2018 Jan 20;144:349-358.

Ferri M, Liscio P, Carotti A, Asciutti S, Sardella R, Macchiarulo A, Camaioni E.

Targeting Wnt-driven cancers: Discovery of novel tankyrase inhibitors.

Eur J Med Chem. 2017 Dec 15;142:506-522

Falchi F, Giacomini E, Masini T, Boutard N, Di Ianni L, Manerba M, Farabegoli F, Rossini L, Robertson J, Minucci S, Pallavicini I, Di Stefano G, Roberti M, Pellicciari R, Cavalli A.

Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors.

ACS Chem Biol. 2017 Oct 20;12(10):2491-2497.

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 DeacetylaseSirtuin 2: Structure-Activity Relationship, X-ray Crystal Structure, and Anticancer Activity.

J Med Chem. 2017 Mar 23;60(6):2344-2360.

Pellicciari R, Passeri D, De Franco F, Mostarda S, Filipponi P, Colliva C, Gadaleta RM, Franco P, Carotti A, Macchiarulo A, Roda A, Moschetta A, Gioiello A.

Discovery of 3α,7α,11β-Trihydroxy-6α-ethyl-5β-cholan-24-oic Acid (TC-100), a Novel Bile Acid as Potent and Highly Selective FXR Agonist for Enterohepatic Disorders.

J Med Chem. 2016 Oct 4.

Passeri D, Camaioni E, Liscio P, Sabbatini P, Ferri M, Carotti A, Giacchè N, Pellicciari R, Gioiello A, Macchiarulo A.

Concepts and Molecular Aspects in the Polypharmacology of PARP-1 Inhibitors.

ChemMedChem. 2016 Jun 20;11(12):1219-26.

Bijsmans IT, Guercini C, Ramos Pittol JM, Omta W, Milona A, Lelieveld D, Egan DA, Pellicciari R, Gioiello A, van Mil SW.

The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression.

Sci Rep. 2015 Sep 15;5:14086.

Liscio P, Carotti A, Asciutti S, Ferri M, Pires MM, Valloscuro S, Ziff J, Clark NR, Macchiarulo A, Aaronson SA, Pellicciari R, Camaioni E.

Scaffold hopping approach on the route to selective tankyrase inhibitors.

Eur J Med Chem. 2014 Nov 24;87:611-23

Marchand JR, Carotti A, Passeri D, Filipponi P, Liscio P, Camaioni E, Pellicciari R, Gioiello A, Macchiarulo A.

Investigating the allosteric reverse signalling of PARP inhibitors with microsecond molecular dynamic simulations and fluorescence anisotropy.

Biochim Biophys Acta. 2014 Oct;1844(10):1765-72.

Gioiello A, Cerra B, Zhang W, Vallerini GP, Costantino G, De Franco F, Passeri D, Pellicciari R, Setchell KD.

Synthesis of atypical bile acids for use as investigative tools for the genetic defect of 3β-hydroxy-Δ(5)-C27-steroid oxidoreductase deficiency.

J Steroid Biochem Mol Biol. 2014 Oct;144 Pt B:348-60. doi: 10.1016/j.jsbmb.2014.06.008.

Macchiarulo A, Gioiello A, Thomas C, Pols TW, Nuti R, Ferrari C, Giacchè N, De Franco F, Pruzanski M, Auwerx J, Schoonjans K, Pellicciari R.

Probing the Binding Site of Bile Acids in TGR5.

ACS Med Chem Lett. 2013 Oct 15;4(12):1158-62. doi: 10.1021/ml400247k.

Roda A, Pellicciari R, Gioiello A, Neri F, Camborata C, Passeri D, De Franco F, Spinozzi S, Colliva C, Adorini L, Montagnani M, Aldini R.

Semisynthetic bile acid FXR and TGR5 agonists: physicochemical properties, pharmacokinetics, and metabolism in the rat.

J Pharmacol Exp Ther. 2014 Jul;350(1):56-68. doi: 10.1124/jpet.114.214650.

Castaldo C, Benicchi T, Otrocka M, Mori E, Pilli E, Ferruzzi P, Valensin S, Diamanti D, Fecke W, Varrone M, Porcari V

CXCR4 Antagonists: A Screening Strategy for Identification of Functionally Selective Ligands.

J Biomol Screen. 2014 Jul;19(6):859-69. doi: 10.1177/1087057114526283.

Sabbatini P, Filipponi P, Sardella R, Natalini B, Nuti R, Macchiarulo A, Pellicciari R, Gioiello A.

Synthesis and quantitative structure-property relationships of side chain-modified hyodeoxycholic acid derivatives.

Molecules. 2013 Aug 30;18(9):10497-513. doi: 10.3390/molecules180910497.

Bartolini D, Stabile AM, Migni A, Gurrado F, Lioci G, De Franco F, Mandarano M, Svegliati-Baroni G, Di Cristina M, Bellezza G, Rende M, Galli F.

Subcellular distribution and Nrf2/Keap1-interacting properties of Glutathione S-transferase P in hepatocellular carcinoma.

Arch Biochem Biophys. 2024 Jul;757:110043. doi: 10.1016/j.abb.2024.110043.