Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins

Guoping Wang; Zaneta Nikolovska-Coleska; Chao Yie Yang; Renxiao Wang; Guozhi Tang; Jie Guo; Sanjeev Shangary; Su Qiu; Wei Gao; Dajun Yang; Jennifer Meagher; Jeanne Stuckey; Krzysztof Krajewski; Sheng Jiang; Peter P. Roller; Hatice Ozel Abaan; York Tomita; Shaomeng Wang

doi:10.1021/jm060460o

Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins

Guoping Wang, Zaneta Nikolovska-Coleska, Chao Yie Yang, Renxiao Wang, Guozhi Tang, Jie Guo, Sanjeev Shangary, Su Qiu, Wei Gao, Dajun Yang, Jennifer Meagher, Jeanne Stuckey, Krzysztof Krajewski, Sheng Jiang, Peter P. Roller, Hatice Ozel Abaan, York Tomita, Shaomeng Wang

Research output: Contribution to journal › Article › peer-review

280 Scopus citations

Abstract

A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a K_i value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC₅₀ value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

Original language	English
Pages (from-to)	6139-6142
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	21
DOIs	https://doi.org/10.1021/jm060460o
State	Published - Oct 2006
Externally published	Yes

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10.1021/jm060460o

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Wang, G., Nikolovska-Coleska, Z., Yang, C. Y., Wang, R., Tang, G., Guo, J., Shangary, S., Qiu, S., Gao, W., Yang, D., Meagher, J., Stuckey, J., Krajewski, K., Jiang, S., Roller, P. P., Abaan, H. O., Tomita, Y., & Wang, S. (2006). Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. Journal of Medicinal Chemistry, 49(21), 6139-6142. https://doi.org/10.1021/jm060460o

@article{f6a8a64f501c46eda661ce7c80392f95,

title = "Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins",

abstract = "A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a Ki value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner.",

author = "Guoping Wang and Zaneta Nikolovska-Coleska and Yang, \{Chao Yie\} and Renxiao Wang and Guozhi Tang and Jie Guo and Sanjeev Shangary and Su Qiu and Wei Gao and Dajun Yang and Jennifer Meagher and Jeanne Stuckey and Krzysztof Krajewski and Sheng Jiang and Roller, \{Peter P.\} and Abaan, \{Hatice Ozel\} and York Tomita and Shaomeng Wang",

year = "2006",

month = oct,

doi = "10.1021/jm060460o",

language = "英语",

volume = "49",

pages = "6139--6142",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "21",

}

Wang, G, Nikolovska-Coleska, Z, Yang, CY, Wang, R, Tang, G, Guo, J, Shangary, S, Qiu, S, Gao, W, Yang, D, Meagher, J, Stuckey, J, Krajewski, K, Jiang, S, Roller, PP, Abaan, HO, Tomita, Y & Wang, S 2006, 'Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins', Journal of Medicinal Chemistry, vol. 49, no. 21, pp. 6139-6142. https://doi.org/10.1021/jm060460o

TY - JOUR

T1 - Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins

AU - Wang, Guoping

AU - Nikolovska-Coleska, Zaneta

AU - Yang, Chao Yie

AU - Wang, Renxiao

AU - Tang, Guozhi

AU - Guo, Jie

AU - Shangary, Sanjeev

AU - Qiu, Su

AU - Gao, Wei

AU - Yang, Dajun

AU - Meagher, Jennifer

AU - Stuckey, Jeanne

AU - Krajewski, Krzysztof

AU - Jiang, Sheng

AU - Roller, Peter P.

AU - Abaan, Hatice Ozel

AU - Tomita, York

AU - Wang, Shaomeng

PY - 2006/10

Y1 - 2006/10

N2 - A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a Ki value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

AB - A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a Ki value of 290 nM and also to Bcl-xL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner.

UR - https://www.scopus.com/pages/publications/33750112776

U2 - 10.1021/jm060460o

DO - 10.1021/jm060460o

M3 - 文章

C2 - 17034116

AN - SCOPUS:33750112776

SN - 0022-2623

VL - 49

SP - 6139

EP - 6142

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 21

ER -

Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins

Abstract

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