T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer.

Abstract:

:A chemokine receptor, CXCR4, and its endogenous ligand, stromal cell-derived factor-1 (SDF-1), have been recognized to be involved in the metastasis of several types of cancers. T140 analogs are peptidic CXCR4 antagonists composed of 14 amino acid residues that were previously developed as anti-HIV agents having inhibitory activity against HIV-entry through its co-receptor, CXCR4. Herein, we report that these compounds effectively inhibited SDF-1-induced migration of human breast cancer cells (MDA-MB-231), human leukemia T cells (Sup-T1) and human umbilical vein endothelial cells at concentrations of 10-100 nM in vitro. Furthermore, slow release administration by subcutaneous injection using an Alzet osmotic pump of a potent and bio-stable T140 analog, 4F-benzoyl-TN14003, gave a partial, but statistically significant (P

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Tamamura H,Hori A,Kanzaki N,Hiramatsu K,Mizumoto M,Nakashima H,Yamamoto N,Otaka A,Fujii N

doi

10.1016/s0014-5793(03)00824-x

keywords:

subject

Has Abstract

pub_date

2003-08-28 00:00:00

pages

79-83

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S001457930300824X

journal_volume

550

pub_type

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