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ChemoBOOM SIGNED

Development of Palladium-Labile Prodrugs for Bioorthogonally-Activated Chemotherapy

Total Cost €

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EC-Contrib. €

0

Partnership

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 ChemoBOOM project word cloud

Explore the words cloud of the ChemoBOOM project. It provides you a very rough idea of what is the project "ChemoBOOM" about.

mandatory    cancers    primary    pill    treat    bioorthogonal    functional    full    reduce    capacity    boom    treatment    pioneered    conventional    intent    unspecificity    mask    reactivation    prodrug    labile    insufficient    release    difficult    pharmacological    forms    paradigm    selective    remission    nonetheless    stage    cancer    strategies    becomes    neoplastic    aggressive    agents    synergistic    broceta    cell    medicinal    emerged    single    experimental    ineffective    strategy    molecule    site    disease    tumours    precursors    advantage    death    explore    culture    unciti    clinically    systemic    drugs    dose    activate    classic    patient    mode    biology    drug    prodrugs    inhibition    first    heterogeneous    levels    cytotoxic    propargylation    last    adverse    area    limiting    activation    tackle    scope    complete    designed    context    heterogeneity    group    evolve    responsible    originated    palladium    chemical    action    chemistry    organometallic    molecular    chemotherapeutic    catalysis    groups    msca    edinburgh   

Project "ChemoBOOM" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF EDINBURGH 

Organization address
address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL
website: www.ed.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.boomchemistry.com/
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-02-01   to  2018-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) coordinator 183˙454.00

Map

 Project objective

The heterogeneity and capacity to evolve in response to treatment of the most aggressive forms of cancer make the selective inhibition of molecular targets an insufficient strategy to reach complete neoplastic remission. In this context, the unspecificity of classic chemotherapeutic agents becomes an advantage for treatment. Nonetheless, due to dose-limiting adverse effects, chemotherapeutic drugs become ineffective against some late-stage primary tumours, which are typically responsible for the death of the patient. To tackle those difficult to treat cancers, improved chemotherapeutic strategies far beyond the one-pill paradigm are mandatory. To reduce systemic side effects while increasing the levels of drug in the disease area, a number of novel methods originated from the Chemical Biology field (rather than from conventional Medicinal Chemistry approaches) have emerged during the last year to explore the site-specific activation of cytotoxic drugs. One of those novel concepts, pioneered by the Unciti-Broceta’s group in Edinburgh, is based on the use of palladium to activate drug precursors by heterogeneous bioorthogonal organometallic (BOOM) catalysis. Using an O-propargylation strategy to mask functional groups essential for the cytotoxic mode of action of clinically-used drugs, I will investigate the development of novel bioorthogonal palladium-labile prodrugs and their reactivation in cancer cell culture by heterogeneous palladium catalysis. With the support of a MSCA-IF, I intent to explore the full scope of this exciting experimental strategy, including the first ever approach designed to release two cytotoxic drugs with synergistic pharmacological activity from a single prodrug molecule.

 Publications

year authors and title journal last update
List of publications.
2017 Ana M. Pérez-López, Belén Rubio-Ruiz, Víctor Sebastián, Lloyd Hamilton, Catherine Adam, Thomas L. Bray, Silvia Irusta, Paul M. Brennan, Guy C. Lloyd-Jones, Dirk Sieger, Jesús Santamaría, Asier Unciti-Broceta
Gold-Triggered Uncaging Chemistry in Living Systems
published pages: 12548-12552, ISSN: 1433-7851, DOI: 10.1002/anie.201705609
Angewandte Chemie International Edition 56/41 2019-06-14
2016 Belén Rubio-Ruiz, Jason T. Weiss, Asier Unciti-Broceta
Efficient Palladium-Triggered Release of Vorinostat from a Bioorthogonal Precursor
published pages: 9974-9980, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01426
Journal of Medicinal Chemistry 59/21 2019-06-14
2018 Belén Rubio-Ruiz, Ana M. Pérez-López, Thomas L. Bray, Martin Lee, Alan Serrels, Martín Prieto, Manuel Arruebo, Neil O. Carragher, Víctor Sebastián, Asier Unciti-Broceta
High-Precision Photothermal Ablation Using Biocompatible Palladium Nanoparticles and Laser Scanning Microscopy
published pages: 3341-3348, ISSN: 1944-8244, DOI: 10.1021/acsami.7b17282
ACS Applied Materials & Interfaces 10/4 2019-06-14

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