Dual Targeting Approach Using 4-Hydroxytamoxifen Neuropeptide Y Conjugates for Selective Addressing of Adipose Tissue.

ABSTRACT: Tamoxifen, a selective estrogen receptor modulator, reduces fat mass and induces adipose tissue browning in obese mice, suggesting its potential as an antiobesity drug. However, small-molecule therapies often cause nonspecific side effects. The goal is to transport 4-hydroxytamoxifen (4-OHT) specifically into cells using the human neuropeptide Y (NPY) receptor type 1 (hY₁R), which is highly expressed on the surface of adipocytes. NPY conjugates are generated that link 4-OHT with three enzymatically cleavable and one self-immolative diamine linkers. All conjugates exhibit similar behavior regarding receptor activation and internalization. The activity of the intracellularly released 4-OHT is measured using a luciferase reporter gene assay. The diamine linker construct is the only

SUBMITTER: Kohler A 

PROVIDER: S-EPMC12711160 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature