Research
Chemical Biology, Covalent ligands, Induced Proximity, PHOSTACs, Drug Discovery, High throughput screening
Interests
Building on a track-record in covalent drug discovery (The Future of Covalent Drugs, Discovery Report Q3, C&EN, 2022), the De Vita group aims at integrating the advantages of small molecule covalent ligands to advance novel applications in Chemical Biology and Drug Discovery. We are interested in developing novel assays and techniques to discover and optimise small molecule covalent binders for challenging targets, which have potential applications in the rising field of chemically induced proximity. Furthermore, we are constantly on the look for Chemical Biology methodologies that will enable understanding of small molecule and protein function in cells with a translational perspective.
Current research lines are focused on PHOSphorylation TArgeting Chimeras (PHOSTACs), a chemically induced proximity approach that employs bifunctional ligands to recruit a protein phosphatase (PP) in the proximity of a phosphorylated protein of interest to drive targeted protein dephosphorylation. Small molecule PHOSTACs will be developed to uncover the role of the unknown phosphoproteome, which still represents the majority of all known phosphosites profiled in humans to date. Mainly focusing on cancer research, we aim to further study the mechanism of action of PHOSTACs and develop ligands with improved pharmacological properties to explore novel therapeutic opportunities in cancer, where protein hyperphosphorylation is a well-known driver of disease.
Publications
Publications of specific relevance to the Centre for Molecular Cell Biology
2024
What is chemical biology?Antolin AA, Aye Y, Bar-Peled L,
De Vita E, Dudkina N, Jewett MC, Kiely-Collins H, Mazitschek R and Zhang ZJ
Cell Chemical Biology,
Elsevier vol. 31 (9), 1562-1565.
01-09-2024Structure-Guided Design and Optimization of Covalent VHL-Targeted Sulfonyl Fluoride PROTACsShah RR,
De Vita E, Sathyamurthi PS, Conole D, Zhang X, Fellows E, Dickinson ER, Fleites CM, Queisser MA, Harling JD and Tate EW
Journal of Medicinal Chemistry,
American Chemical Society (Acs) vol. 67 (6), 4641-4654.
13-03-2024 2022
A KLK6 Activity-Based Probe Reveals a Role for KLK6 Activity in Pancreatic Cancer Cell InvasionZhang L, Lovell S,
De Vita E, Jagtap PKA, Lucy D, Grocin AG, Kjær S, Borg A, Hennig J, Miller AK and Tate EW
Journal of The American Chemical Society,
American Chemical Society (Acs) vol. 144 (49), 22493-22504.
22-11-2022 Identification of the first structurally validated covalent ligands of the small GTPase RAB27AJamshidiha M, Lanyon-Hogg T, Sutherell CL, Craven GB, Tersa M,
De Vita E, Brustur D, Pérez-Dorado I, Hassan S, Petracca R, Morgan RM, Sanz-Hernández M, Norman JC, Armstrong A, Mann DJ, Cota E and Tate EW
Rsc Medicinal Chemistry,
Royal Society of Chemistry (Rsc) vol. 13 (2), 150-155.
01-01-2022 Light-mediated multi-target protein degradation using arylazopyrazole photoswitchable PROTACs (AP-PROTACs)Zhang Q, Kounde CS, Mondal M, Greenfield JL, Baker JR, Kotelnikov S, Ignatov M, Tinworth CP, Zhang L, Conole D,
De Vita E, Kozakov D, McCluskey A, Harling JD, Fuchter MJ and Tate EW
Chemical Communications,
Royal Society of Chemistry (Rsc) vol. 58 (78), 10933-10936.
01-01-2022 2021
Blocking Kallikrein 6 promotes developmental myelinationYoon H, Triplet EM, Simon WL, Choi C, Kleppe LS,
De Vita E, Miller AK and Scarisbrick IA
Glia,
Wiley vol. 70 (3), 430-450.
09-10-2021 Beyond targeted protein degradation: LD·ATTECs clear cellular lipid dropletsDe Vita E, Lucy D and Tate EW
Cell Research,
Springer Nature vol. 31 (9), 945-946.
05-08-2021 A Suite of Activity-Based Probes To Dissect the KLK Activome in Drug-Resistant Prostate CancerLovell S, Zhang L, Kryza T, Neodo A, Bock N,
De Vita E, Williams ED, Engelsberger E, Xu C, Bakker AT, Maneiro M, Tanaka RJ, Bevan CL, Clements JA and Tate EW
Journal of The American Chemical Society,
American Chemical Society (Acs) vol. 143 (23), 8911-8924.
04-06-2021 PROTACs, molecular glues and bifunctionals from bench to bedside: Unlocking the clinical potential of catalytic drugsManeiro M,
De Vita E, Conole D, Kounde CS, Zhang Q and Tate EW
67-190.
01-01-2021 Development of a fluorogenic ADAMTS-7 substrateSantamaria S, Buemi F, Nuti E, Cuffaro D,
De Vita E, Tuccinardi T, Rossello A, Howell S, Mehmood S, Snijders AP and de Groot R
Journal of Enzyme Inhibition and Medicinal Chemistry,
Taylor & Francis vol. 36 (1), 2160-2169.
01-01-2021 2020
10 years into the resurgence of covalent drugsDe Vita E Future Medicinal Chemistry,
Taylor & Francis vol. 13 (2), 193-210.
04-12-2020 The Missing Link between (Un)druggable and Degradable KRASDe Vita E, Maneiro M and Tate EW
Acs Central Science,
American Chemical Society (Acs) vol. 6 (8), 1281-1284.
03-08-2020 2019
Synthesis and Structure‐Activity Relationships of N‐(4‐Benzamidino)‐Oxazolidinones: Potent and Selective Inhibitors of Kallikrein‐Related Peptidase 6De Vita E, Smits N, van den Hurk H, Beck EM, Hewitt J, Baillie G, Russell E, Pannifer A, Hamon V, Morrison A, McElroy SP, Jones P, Ignatenko NA, Gunkel N and Miller AK
Chemmedchem,
Wiley vol. 15 (1), 79-95.
18-11-2019 Design and Synthesis of Ionic Liquid‐Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI‐Coated Gold NanoparticlesD'Andrea F, Nuti E, Becherini S, Cuffaro D, Husanu E, Camodeca C,
De Vita E, Zocchi MR, Poggi A, D'Arrigo C, Cappello V, Gemmi M, Nencetti S, Chiappe C and Rossello A
Chemmedchem,
Wiley vol. 14 (6), 686-698.
14-02-2019 2018
Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular ActivityDe Vita E, Schüler P, Lovell S, Lohbeck J, Kullmann S, Rabinovich E, Sananes A, Heßling B, Hamon V, Papo N, Hess J, Tate EW, Gunkel N and Miller AK
Journal of Medicinal Chemistry,
American Chemical Society (Acs) vol. 61 (19), 8859-8874.
13-09-2018 A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineeringSananes A, Cohen I, Shahar A, Hockla A,
De Vita E, Miller AK, Radisky ES and Papo N
Journal of Biological Chemistry,
Elsevier vol. 293 (33), 12663-12680.
22-06-2018 Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometryLonguespée R, Wefers AK,
De Vita E, Miller AK, Reuss DE, Wick W, Herold-Mende C, Kriegsmann M, Schirmacher P, von Deimling A and Pusch S
Acta Neuropathologica Communications,
Springer Nature vol. 6 (1)
02-03-2018
