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https://hdl.handle.net/123456789/1829| Τύπος: | Αναρτημένη ανακοίνωση (poster) |
| Τίτλος: | Targeting the kynurenine pathway for tumour detection and characterization by PET and SPECT |
| Συγγραφέας: | [EL] Φώσκολου, Αγγελική-Σοφία[EN] Foskolou, Angeliki-Sofia [EL] Γεωργίου, Μαρία[EN] Georgiou, Maria [EL] Γκιώνης, Στέλιος[EN] Gkionis, Stelios [EL] Ρούπα, Ιωάννα[EN] Roupa, Ioanna [EL] Πιρμεττής, Ιωάννης[EN] Pirmettis, Ioannis [EL] Παπαδόπουλος, Μηνάς[EN] Papadopoulos, Minas [EL] Χιωτέλλης, Αριστείδης[EN] Chiotellis, Aristeidis |
| Ημερομηνία: | 29/11/2021 |
| Περίληψη: | In mammals and other vertebrates, three enzymes, IDO1, IDO2 and TDO, catalyze the rate-limiting first step of tryptophan catabolism down the kynurenine pathway (KP) which accounts for >95% of tryptophan degradation. Enhanced tryptophan catabolism in human cancers, mediated by activation of these enzymes, has been shown to be fundamental in the ability of tumours to breach the defence mechanisms of the immune system. As part of immunomodulating anticancer therapies, selective inhibitors have reached late-stage clinical trials (especially for IDO1). Recently though, research in the field has been shifting towards the development of dual IDO1/TDO and or pan-inhibitors since emerging evidence indicates that TDO and IDO2 are jointly activated with IDO1 in many tumours.1 However, there are no currently available biomarkers for monitoring response to KP-targeted therapies and since patient stratification is clearly important, as these inhibitors will work only if KP is activated, the lack of appropriate clinical tools to monitor KP activity before and during treatment becomes evident. In this work, we report on the pre-clinical development of PET and SPECT tracers as possible tools for the non-invasive imaging of KP in cancer with potential applications for tumour detection and characterization.The designed 18F-PET tracers 1 and 2 and 99mTc-SPECT tracer 3 (Figure below) are based on the pharmacophore structure of diaryl hydroxylamines whose potential for dual and/or pan inhibition was recently shown.2 Reference compounds and precursors for radiolabelling were synthesized by following multi-step synthetic procedures. Enzyme-based assays identified the references of 1 and 2 as dual IDO1/TDO inhibitors (IC50: 0.37μM and 0.57μM for IDO1, 16.1μM and 9.9μM for TDO) while 3 was identified as an IDO1 inhibitor (IC50: 10μM). Cell-based assays for IDO1 support these results. Preliminary radiosynthesis showed successful 18F-radiolabelling for 1. Preliminary results show successful 18F-radiosynthesis for 1. On-going efforts are focusing on the radiosynthesis of 2 and 3 and the in vivo evaluation of 1-3 in tumour bearing mice |
| Γλώσσα: | Αγγλικά |
| Τόπος δημοσίευσης: | Virtually |
| Σελίδες: | 13 |
| Θεματική κατηγορία: | [EL] Ανακάλυψη και Ανάπτυξη φαρμάκων[EN] Drug Discovery |
| Λέξεις-κλειδιά: | PET imaging; fluorine-18; kynurenine; IDO |
| Κάτοχος πνευματικών δικαιωμάτων: | © The Author(s) 2021 |
| Όνομα εκδήλωσης: | 13th AFMC International Medicinal Chemistry Symposium (AIMECS 2021) |
| Τοποθεσία εκδήλωσης: | Online |
| Ημ/νία έναρξης εκδήλωσης: | 29/11/2021 |
| Ημ/νία λήξης εκδήλωσης: | 02/12/2021 |
| Σημειώσεις: | https://biz.knt.co.jp/tour/2021/11/aimecs/index.html “This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» (MIS 5047830).’’ |
| Εμφανίζεται στις συλλογές: | Ερευνητικές ομάδες |
Αρχεία σε αυτό το τεκμήριο:
| Αρχείο | Περιγραφή | Σελίδες | Μέγεθος | Μορφότυπος | Έκδοση | Άδεια | |
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| Chiotellis_AIMECS2021.pdf | 4.18 MB | Adobe PDF | - |  | Δείτε/ανοίξτε |