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

By Jia‐Lun Wang, Dongxiang Liu, Zhijia Zhang, S. Shan, Xiaobing Han, S. Srinivasula, Carlo Maria Croce, E. Alnemri, Ziwei Huang. Proceedings of the National Academy of Sciences of the United States of America, 2000

1,172 citations recorded by the source corpus.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2ea5c9d8a64eedd685a26018502154380042ed28

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Molecular Biology

Citations in the corpus

From bench to clinic with apoptosis-based therapeutic agents (2000, background): “Even so, small molecules with a high affinity for the binding cleft of the Bcl-2 homology (BH) domain BH3 on the surface of Bcl-2 seem to induce apoptosis in cultured cell”
Targeting mitochondria for cancer therapy (2010, background): “HA14-1 (2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4 H -chromene-3-carboxylate) is an organic compound that was identified as a BCL-2 interactor with specific BCL-2 inhibitory function”
The Bcl2 family: regulators of the cellular life-or-death switch (2002, background): “Several reports have already described small organic molecules that bind to Bcl2 in vitro (albeit with low affinity) and compromise cell viabilit”
Selectivity by Small-Molecule Inhibitors of Protein Interactions Can Be Driven by Protein Surface Fluctuations (2015, neutral): “Plasticity of the protein surface allows recognition of diverse chemical scaffolds There have been dozens of reported inhibitors of Bcl-2 family members (18, 19, 97-115), spanning a broad range of chemotypes.”
Apoptosis-based therapies (2002, background): “cgi?l=598">BCL-X L and promote apoptosis of cancer cell”
Apoptosis A Link between Cancer Genetics and Chemotherapy (2002, background): “Exploiting the genetic and/or physiological differences between tumor and heterodimerization leading to cytochrome c release, have now been developed (Wang et al., 2000).”
The Bcl-2 family: roles in cell survival and oncogenesis (2003, background): “The concept that this domain alone is sufficient to inactivate Bcl-2 and provoke cell death has been supported by studies delivering BH3 peptides (Cosulich et al., 1997; Holinger et al., 1999; Wang et al., 2000b; Polster et al., 2001; Letai et al., 2002; Vieira et al., 2002).”
The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. (2006, background): “In contrast, Bax/Bak-deficient cells were as sensitive as WT ones to killing by several small chemical entities reported to be BH3 mimetics: HA14-1 (Wang et al., 2000), BH3I-1 (Degterev et al., 2001), Compound 6 (Enyedy et al., 2001), Antimycin A (Tzung et al., 2001), Chelerythrine (Chan et al., 200”
Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy (2006, background): “Screening of a chemical library for compounds able to bind to the BH3 pocket of Bcl-2 proteins resulted in the identification of HA14-1, a compound that competes with Bak for the binding to Bcl-2 (Wang et al., 2000).”