Identification of Simple Compounds with Microtubule-Binding Activity That Inhibit Cancer Cell Growth with High Potency

被引：65

作者：

Yang, Wan Seok ^{[1
]}

Shimada, Kenichi ^{[1
]}

Delva, Darnelle ^{[1
]}

Patel, Milesh ^{[1
]}

Ode, Egberamwen ^{[1
]}

Skouta, Rachid ^{[2
]}

Stockwell, Brent R. ^{[1
,2
,3
]}

机构：

[1] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[2] Columbia Univ, Dept Chem, New York, NY 10027 USA

[3] Columbia Univ, Howard Hughes Med Inst, New York, NY 10027 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2012年 / 3卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Small molecules; cell-based screening; microtubule; anticancer drug leads; MULTIDRUG-RESISTANCE; TUMOR-CELLS; IN-VITRO; AGENTS; APOPTOSIS; DEATH;

D O I：

10.1021/ml200195s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We analyzed more than 1 million small molecules with the goal of finding simple synthetic compounds that potently inhibit cancer cell growth. We identified three such compounds with unknown mechanisms of action. Subsequent studies revealed that all three of these small molecules target microtubules. These three scaffolds can serve as templates for developing new microtubule-targeted agents, overcoming the limits of existing microtubule-inhibiting drugs derived from complex natural products.

引用

页码：35 / 38

页数：4

共 20 条

[1] Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells [J].

Dolma, S ;

Lessnick, SL ;

Hahn, WC ;

Stockwell, BR .

CANCER CELL, 2003, 3 (03) :285-296

[2] Microtubule-binding agents: a dynamic field of cancer therapeutics [J].

Dumontet, Charles ;

Jordan, Mary Ann .

NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (10) :790-803

[3] Microtubule targeting agents: Basic mechanisms of multidrug resistance (MDR) [J].

Fojo, AT ;

Menefee, M .

SEMINARS IN ONCOLOGY, 2005, 32 (06) :S3-S8

[4] PHARMACOLOGICAL CIRCUMVENTION OF MULTIDRUG-RESISTANCE [J].

FORD, JM ;

HAIT, WN .

CYTOTECHNOLOGY, 1993, 12 (1-3) :171-212

[5] AGENTS WHICH REVERSE MULTIDRUG-RESISTANCE ARE INHIBITORS OF [H-3] VINBLASTINE TRANSPORT BY ISOLATED VESICLES [J].

HORIO, M ;

LOVELACE, E ;

PASTAN, I ;

GOTTESMAN, MM .

BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1061 (01) :106-110

[6]

Jiang JD, 1998, CANCER RES, V58, P5389

[7] Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials [J].

Johnson, JI ;

Decker, S ;

Zaharevitz, D ;

Rubinstein, LV ;

Venditti, J ;

Schepartz, S ;

Kalyandrug, S ;

Christian, M ;

Arbuck, S ;

Hollingshead, M ;

Sausville, EA .

BRITISH JOURNAL OF CANCER, 2001, 84 (10) :1424-1431

[8] Can the pharmaceutical industry reduce attrition rates? [J].

Kola, I ;

Landis, J .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (08) :711-715

[9] A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities [J].

Li, PK ;

Pandit, B ;

Sackett, DL ;

Hu, ZG ;

Zink, J ;

Zhi, JD ;

Freeman, D ;

Robey, RW ;

Werbovetz, K ;

Lewis, A ;

Li, CL .

MOLECULAR CANCER THERAPEUTICS, 2006, 5 (02) :450-456

[10] Microtubules, microtubule-interfering agents and apoptosis [J].

Mollinedo, F ;

Gajate, C .

APOPTOSIS, 2003, 8 (05) :413-450

← 1 2 →