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Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy.
Abyar, Selda; Huang, Luojiao; Husiev, Yurii; Bretin, Ludovic; Chau, Bobby; Ramu, Vadde; Wildeman, Jacob Hendricus; Belfor, Kimberley; Wijaya, Lukas S; van der Noord, Vera E; Harms, Amy C; Siegler, Maxime A; Le Dévédec, Sylvia E; Bonnet, Sylvestre.
Afiliación
  • Abyar S; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Huang L; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Husiev Y; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Bretin L; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Chau B; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Ramu V; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Wildeman JH; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Belfor K; Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Wijaya LS; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • van der Noord VE; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Harms AC; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Siegler MA; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Le Dévédec SE; Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, PO Box 9502, Leiden 2300 RA, The Netherlands.
  • Bonnet S; Department of Chemistry, Johns Hopkins University, 3400 N Charles St, Baltimore, Maryland 21218, United States.
J Med Chem ; 67(13): 11086-11102, 2024 Jul 11.
Article en En | MEDLINE | ID: mdl-38924492
ABSTRACT
Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts the ruthenium cage and the cytotoxic inhibitor STF31. This study shows that Ru-STF31 can significantly decrease intracellular NAD+ levels in both normoxic (21% O2) and hypoxic (1% O2) U87MG cells. Strikingly, NAD+ depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD+. Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxígeno / Rutenio / Nicotinamida Fosforribosiltransferasa / NAD / Antineoplásicos Límite: Humans Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxígeno / Rutenio / Nicotinamida Fosforribosiltransferasa / NAD / Antineoplásicos Límite: Humans Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos