Prostate
cancer is the second most common type of cancer among
men. Its main method of treatment is chemotherapy, which has a wide
range of side effects. One of the solutions to this challenge is targeted
delivery to prostate cancer cells. Here we synthesized a novel small-molecule
PSMA-targeted conjugate based on the monomethyl auristatin E. Its
structure and conformational properties were investigated by NMR spectroscopy.
Cytotoxicity, intracellular reactive oxygen species induction, and
stability under liver microsomes and P450-cytochrome species were
investigated for this conjugate. The conjugate demonstrated 77–85%
tumor growth inhibition levels on 22Rv1 (PSMA (+)) xenografts, compared
with a 37% inhibition level on PC-3 (PSMA (−)) xenografts,
in a single dose of 0.3 mg/kg and a sufficiently high therapeutic
index of 21. Acute, chronic, and subchronic toxicities and pharmacokinetics
have shown that the synthesized conjugate is a promising potential
agent for the chemotherapy of prostate cancer.
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