A novel atypical retinoid endowed with proapoptotic and antitumor activity.

Abstract

The novel atypical retinoid E-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926, 4) exhibited a potent antiproliferative activity on a large panel of human tumor cells. Despite almost complete loss of ability to activate RARs, the compound was an effective apoptosis inducer and surprisingly produced DNA damage, that likely contributes to the proapoptotic activity. Following oral administration, 4 was well tolerated and caused tumor growth inhibition in the ovarian carcinoma, A2780/DX, and in the human melanoma, MeWo, growing in nude mice, thus supporting the therapeutic interest of the novel agent.

• Authors: Raffaella Cincinelli, Sabrina Dallavalle, Lucio Merlini, Sergio Penco, Claudio Pisano, Paolo Carminati, Giuseppe Giannini, Loredana Vesci, Carlo Gaetano, Barbara Illy, Valentina Zuco, Rosanna Supino, Franco Zunino
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 46 Issue 6 Pg. 909-12 (Mar 13 2003) ISSN: 0022-2623 [Print] United States
• PMID: 12620066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
• Antineoplastic Agents
• Cinnamates
• Protein Isoforms
• Receptors, Retinoic Acid
• Retinoids
• Adamantane

Topics

• Adamantane (analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis
• Cinnamates (chemical synthesis, chemistry, pharmacology)
• DNA Damage
• Drug Screening Assays, Antitumor
• Female
• Humans
• Melanoma (drug therapy, pathology)
• Mice
• Mice, Nude
• Ovarian Neoplasms (drug therapy, pathology)
• Protein Isoforms
• Receptors, Retinoic Acid (genetics, metabolism)
• Retinoids (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Transfection
• Transplantation, Heterologous
• Tumor Cells, Cultured