Academic Journal
Exploiting PKM2-PARP1 dependency: Isoselenazolium-olaparib conjugates achieve multimodal PKM2 suppression.
| Τίτλος: | Exploiting PKM2-PARP1 dependency: Isoselenazolium-olaparib conjugates achieve multimodal PKM2 suppression. |
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| Συγγραφείς: | Dimitrijevs P; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV1006, Riga, Latvia., Makrecka-Kuka M; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV1006, Riga, Latvia., Zelencova-Gopejenko D; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV1006, Riga, Latvia., Rudevica Z; Latvian Biomedical Research and Study Centre, LV-1067, Riga, Latvia., Korotkaja K; Latvian Biomedical Research and Study Centre, LV-1067, Riga, Latvia., Zajakina A; Latvian Biomedical Research and Study Centre, LV-1067, Riga, Latvia., Rudzitis K; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV1006, Riga, Latvia., Bogucka A; Department of Biochemistry, Sanger Building, 80 Tennis Ct Rd, Cambridge, CB2 1GA, University of Cambridge, UK., Hyvönen M; Department of Biochemistry, Sanger Building, 80 Tennis Ct Rd, Cambridge, CB2 1GA, University of Cambridge, UK., Pantelejevs T; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV1006, Riga, Latvia., Arsenyan P; Latvian Institute of Organic Synthesis, Aizkraukles 21, LV1006, Riga, Latvia. Electronic address: pavel@osi.lv. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109962. Date of Electronic Publication: 2026 May 09. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Poly (ADP-Ribose) Polymerase-1*/metabolism , Poly (ADP-Ribose) Polymerase-1*/antagonists & inhibitors , Poly(ADP-ribose) Polymerase Inhibitors*/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors*/chemistry , Poly(ADP-ribose) Polymerase Inhibitors*/chemical synthesis , Carrier Proteins*/metabolism , Carrier Proteins*/antagonists & inhibitors , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/chemical synthesis , Thyroid Hormones*/metabolism , Membrane Proteins*/metabolism , Membrane Proteins*/antagonists & inhibitors , Organoselenium Compounds*/pharmacology , Organoselenium Compounds*/chemistry , Piperazines*/pharmacology , Piperazines*/chemistry, Cell Proliferation/drug effects ; Humans ; Thyroid Hormone-Binding Proteins ; Structure-Activity Relationship ; Molecular Structure ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Cell Line, Tumor |
| Περίληψη: | Pyruvate Kinase M2 (PKM2) is a central regulator of glucose metabolism in cancer cells whose function extends beyond glycolysis. PKM2 can translocate to the nucleus, where it acts as an oncogenic transcription factor. In turn, its nuclear retention is enhanced upon binding with poly(ADP-ribose), which is prevented by PARP1 inhibition. To exploit this interplay, a new class of PKM2-PARP1 inhibitor conjugates was designed and synthesized. The lead compound 9f potently inhibited PKM2 and PARP1 (IC (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest No competing interest. |
| Contributed Indexing: | Keywords: Cancer; Metabolic reprogramming; PARP; Pyruvate kinase M2; Selenium |
| Substance Nomenclature: | EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) 0 (Thyroid Hormone-Binding Proteins) EC 2.4.2.30 (PARP1 protein, human) 0 (Poly(ADP-ribose) Polymerase Inhibitors) 0 (Carrier Proteins) 0 (Antineoplastic Agents) 0 (Thyroid Hormones) 0 (Membrane Proteins) 0 (Organoselenium Compounds) 0 (Piperazines) |
| Entry Date(s): | Date Created: 20260512 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.bioorg.2026.109962 |
| PMID: | 42119206 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2026.109962 |