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.
EntreMed, Inc., 9640 Medical Center Drive, Rockville, MD 20850, USA.
Gregory E
GE
Agoston
Jamshed H
JH
Shah
Lita
L
Suwandi
Arthur D
AD
Hanson
Xiaoguo
X
Zhan
Theresa M
TM
LaVallee
Victor
V
Pribluda
Anthony M
AM
Treston
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