A PSMA-targeted doxorubicin small-molecule drug conjugate.
Bioorg Med Chem Lett
; 104: 129712, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38521177
ABSTRACT
We developed a model small-molecule drug conjugate (SMDC) that employed doxorubicin as a representative chemotherapeutic targeted to the cell membrane biomarker PSMA (prostate-specific membrane antigen) expressed on prostate cancer cells. The strategy capitalized on the clatherin-mediated internalization of PSMA to facilitate the selective uptake and release of doxorubicin in the target cells. The SMDC was prepared and assessed for binding kinetics, plasma stability, cell toxicity, and specificity towards PSMA expressing prostate cancer cell lines. We observed high affinity of the SMDC for PSMA (IC50 5 nM) with irreversible binding, as well as specific effectiveness against PSMA(+) cells. These findings validated the strategy for a small molecule-based approach in targeted cancer therapy.
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MEDLINE
Assunto principal:
Neoplasias da Próstata
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Doxorrubicina
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Glutamato Carboxipeptidase II
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Antígenos de Superfície
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article