SAR studies of 2-methoxyestradiol and development of its analogs as probes of anti-tumor mechanisms

被引：13

作者：

Ho, Abby ^{[1
]}

Kim, Yang-eon ^{[1
]}

Lee, Hyosung ^{[1
]}

Cyrus, Kedra ^{[1
]}

Baek, Sun-Hee ^{[1
]}

Kim, Kyung-Bo ^{[1
]}

机构：

[1] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40506 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 13期

关键词：

2-methoxyestradiol; affinity matrix; biotinylation; antitumor estrogen metabolites;

D O I：

10.1016/j.bmcl.2006.04.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The major estrogen metabolite 2-methoxyestradiol (2ME) has been shown to target tumor cells without severe side effects and is currently being evaluated in clinical trials for several types of cancer. Despite its promise for use in clinical setting, the mechanism(s) by which 2ME exerts its anti-tumor activity is not clearly defined at this time. Employing organic chemistry tools, we synthesized 2ME analogs with which 2ME affinity column was prepared, enabling us to detect a protein that selectively interacts with 2ME. This 2ME analog will be useful as a probe to identify the biological target(s) of 2ME and study their functions in tumor cells. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：3383 / 3387

页数：5

共 33 条

[1] Amorino GP, 2000, RADIAT RES, V153, P384, DOI 10.1667/0033-7587(2000)153[0384:EOREIV]2.0.CO
[2] 2
[3] INTERLEUKIN-2 STIMULATION OF P70 S6 KINASE-ACTIVITY IS INHIBITED BY THE IMMUNOSUPPRESSANT RAPAMYCIN
CALVO, V
CREWS, CM
VIK, TA
BIERER, BE
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (16) : 7571 - 7575
[4] Chemical genetics: exploring and controlling cellular processes with chemical probes
Crews, CM
Splittgerber, U
[J]. TRENDS IN BIOCHEMICAL SCIENCES, 1999, 24 (08) : 317 - 320
[5] Small-molecule inhibitors of the cell cycle
Crews, CM
Mohan, R
[J]. CURRENT OPINION IN CHEMICAL BIOLOGY, 2000, 4 (01) : 47 - 53
[6] SYNTHESIS, ANTITUBULIN AND ANTIMITOTIC ACTIVITY, AND CYTOTOXICITY OF ANALOGS OF 2-METHOXYESTRADIOL, AN ENDOGENOUS MAMMALIAN METABOLITE OF ESTRADIOL THAT INHIBITS TUBULIN POLYMERIZATION BY BINDING TO THE COLCHICINE BINDING-SITE
CUSHMAN, M
HE, HM
KATZENELLENBOGEN, JA
LIN, CM
HAMEL, E
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (12) : 2041 - 2049
[7] Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on tubulin polymerization and cancer cell growth
Cushman, M
He, HM
Katzenellenbogen, JA
Varma, RK
Hamel, E
Lin, CM
Ram, S
Sachdeva, YP
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (15) : 2323 - 2334
[8] Effects of altering the electronics of 2-methoxyestradiol on cell proliferation, on cytotoxicity in human cancer cell cultures, and on tubulin polymerization
Edsall, AB
Mohanakrishnan, AK
Yang, DL
Fanwick, PE
Hamel, E
Hanson, AD
Agoston, GE
Cushman, M
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (21) : 5126 - 5139
[9] 2-methoxyestradiol and analogs as novel antiproliferative agents: Analysis of three-dimensional quantitative structure-activity relationships for DNA synthesis inhibition and estrogen receptor binding
Hughes, RA
Harris, T
Altmann, E
McAllister, D
Vlahos, R
Robertson, A
Cushman, M
Wang, ZQ
Stewart, AG
[J]. MOLECULAR PHARMACOLOGY, 2002, 61 (05) : 1053 - 1069
[10] Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer
Huober, JB
Nakamura, S
Meyn, R
Roth, JA
Mukhopadhyay, T
[J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2000, 48 (04): : 1127 - 1137

← 1 2 3 4 →