What question did this study set out to answer?

Identify and characterize a nonpeptidic small molecule designed to bind the Bcl-2 surface pocket and trigger apoptosis in tumor cells.

June 20, 2000Proceedings of the National Academy of SciencesOpen Access

Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells

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Authors

JWJialun Wang DLDongxiang Liu ZZZhijia Zhang

Discussion

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Overview

Preclinical study demonstrates that the small molecule HA14-1 induces apoptosis in Bcl-2-overexpressing leukemia cells, indicating potential for structure-based cancer therapeutics.

Key Points

Identify and characterize a nonpeptidic small molecule designed to bind the Bcl-2 surface pocket and trigger apoptosis in tumor cells.
Screened candidate small molecules in silico based on the predicted three-dimensional surface pocket structure of the Bcl-2 protein.
Assayed in vitro binding of candidate molecule HA14-1 and evaluated its apoptotic effects, mitochondrial membrane potential changes, and caspase activation in HL-60 leukemia cells and Apaf-1-deficient mouse embryonic fibroblasts.
HA14-1 bound the critical Bcl-2 surface pocket and induced apoptosis in Bcl-2-overexpressing HL-60 cells alongside decreased mitochondrial membrane potential and sequential activation of caspase-9 and caspase-3.
HA14-1-mediated cell death was not inhibited by cytokine response modifier A and occurred robustly in Apaf-1(+/+) cells, but was absent in Apaf-1(-/-) cells, confirming an Apaf-1- and caspase-dependent mechanism.

Cite This Study

Wang et al. (2000) studied this question.

synapsesocial.com/papers/69dd5d517808b00a4799d287 https://doi.org/10.1073/pnas.97.13.7124

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June 20, 2000Proceedings of the National Academy of SciencesOpen Access

Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells

View Full Paper

Ask AI

Bookmark

Authors

JWJialun Wang DLDongxiang Liu ZZZhijia Zhang

Discussion

Member takes

Overview

Preclinical study demonstrates that the small molecule HA14-1 induces apoptosis in Bcl-2-overexpressing leukemia cells, indicating potential for structure-based cancer therapeutics.

Key Points

Identify and characterize a nonpeptidic small molecule designed to bind the Bcl-2 surface pocket and trigger apoptosis in tumor cells.
Screened candidate small molecules in silico based on the predicted three-dimensional surface pocket structure of the Bcl-2 protein.
Assayed in vitro binding of candidate molecule HA14-1 and evaluated its apoptotic effects, mitochondrial membrane potential changes, and caspase activation in HL-60 leukemia cells and Apaf-1-deficient mouse embryonic fibroblasts.
HA14-1 bound the critical Bcl-2 surface pocket and induced apoptosis in Bcl-2-overexpressing HL-60 cells alongside decreased mitochondrial membrane potential and sequential activation of caspase-9 and caspase-3.
HA14-1-mediated cell death was not inhibited by cytokine response modifier A and occurred robustly in Apaf-1(+/+) cells, but was absent in Apaf-1(-/-) cells, confirming an Apaf-1- and caspase-dependent mechanism.

Cite This Study

Wang et al. (2000) studied this question.

synapsesocial.com/papers/69dd5d517808b00a4799d287 https://doi.org/10.1073/pnas.97.13.7124

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