2. Academic Validation
  3. Synthesis, antiproliferative, and pharmacokinetic properties of 3- and 17-double-modified analogs of 2-methoxyestradiol

Synthesis, antiproliferative, and pharmacokinetic properties of 3- and 17-double-modified analogs of 2-methoxyestradiol

  • Bioorg Med Chem Lett. 2009 Nov 1;19(21):6241-4. doi: 10.1016/j.bmcl.2009.08.020.
Gregory E Agoston 1,  Jamshed H Shah,  Lita Suwandi,  Arthur D Hanson,  Xiaoguo Zhan,  Theresa M LaVallee,  Victor Pribluda,  Anthony M Treston
Affiliations

Affiliation

  • 1 EntreMed, Inc., 9640 Medical Center Drive, Rockville, MD 20850, USA.
PMID: 19782564 DOI: 10.1016/j.bmcl.2009.08.020
Abstract

The syntheses of 21 analogs of 2-methoxyestradiol are presented, including ENMD-1198 which was selected for advancement into Phase 1 clinical trials in oncology. These analogs were evaluated for antiproliferative activity using breast tumor MDA-MB-231 cells, for antiangiogenic activity in HUVEC proliferation assays, and for estrogenic activity in MCF-7 cell proliferation. The most active analogs were evaluated for iv and oral pharmacokinetic properties via cassette dosing in rat and in mice pharmacokinetic models.

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