Synthesis, antiproliferative, and pharmacokinetic properties of 3- and 17-double-modified analogs of 2-methoxyestradiol.
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.
Agoston
Gregory E
GE
EntreMed, Inc., 9640 Medical Center Drive, Rockville, MD 20850, USA.
Shah
Jamshed H
JH
Suwandi
Lita
L
Hanson
Arthur D
AD
Zhan
Xiaoguo
X
LaVallee
Theresa M
TM
Pribluda
Victor
V
Treston
Anthony M
AM
D000077584:2-Methoxyestradiol; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004963:Estrenes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship
C530263:2-methoxyoestra-1,3,5(10),16-tetraene-3-carboxamide; D018931:Antineoplastic Agents, Hormonal; D004963:Estrenes; D004958:Estradiol; D000077584:2-Methoxyestradiol