| Autor: |
Berthel SJ; Discovery Chemistry, Roche Research Center, Hoffmann-La Roche Inc, Nutley, NJ 07110, USA., Marks IM, Yin X, Mischke SG, Orzechowski L, Pezzoni G, Sala F, Vassilev LT |
| Jazyk: |
angličtina |
| Zdroj: |
Anti-cancer drugs [Anticancer Drugs] 2002 Apr; Vol. 13 (4), pp. 359-66. |
| DOI: |
10.1097/00001813-200204000-00004 |
| Abstrakt: |
Ro 41-4439, a phenyl-pyridine-2-carboxylic acid derivative, was identified by a cell-based screening approach that exploits the differences between normal and cancer cells in their sensitivity to cytotoxic agents. This compound showed low micromolar antiproliferative activity and cytotoxicity against a broad panel of human cancer cell lines in vitro, and over 10-fold selectivity to cancer cells when tested in parallel with a panel of proliferating normal human cells. Cytotoxicity of Ro 41-4439 is due to arrest of cell cycle progression in mitosis followed by induction of apoptosis. Four-week treatment of nude mice bearing established mammary tumor xenografts (MDA-MB-435) with well-tolerated doses of the compound showed 73% inhibition of tumor growth. Limited exploration of structure-activity relationships involving side chain length, and aryl and pyridine rings allowed for the identification of more potent analogs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
