The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis
Open accessAbstract
Elevated expression of members of the BCL-2 pro-survival family of proteins can confer resistance to apoptosis in cancer cells. Small molecule obatoclax (GX15-070), which is predicted to occupy a hydrophobic pocket within the BH3 binding groove of BCL-2, antagonizes these members and induces apoptosis, dependent on BAX and BAK. Reconstitution in yeast confirmed that obatoclax acts on the pathway and overcomes BCL-2-, BCL-XL-, BCL-w-, and MCL-1-mediated resistance to BAX or BAK. The compound potently interfered with the direct interaction between MCL-1 and BAK in intact mitochondrial outer membrane and inhibited the association between MCL-1 and BAK in intact cells. MCL-1 has been shown to confer resistance to the BCL-2/BCL-XL/BCL-w-selective antagonist ABT-737 and to the proteasome inhibitor bortezomib. In both cases, this resistance was overcome by obatoclax. These findings support a rational clinical development opportunity for the compound in cancer indications or treatments where MCL-1 contributes to resistance to cell killing.
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Cites
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Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
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Structural biology of the Bcl-2 family of proteins
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Mcl-1 deficiency results in peri-implantation embryonic lethality
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Cited by
ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor
Tse, C., Shoemaker, A. R., Adickes, J., Anderson, M. G., Chen, J., Jin, S., Johnson, E. F., Marsh, K. C., Mitten, M. J., Nimmer, P., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5836 · Cited by 1,992
Targeting mitochondria for cancer therapy
Fulda, S., Galluzzi, L., & Kroemer, G. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3137 · Cited by 1,629
Natural products to drugs: natural product-derived compounds in clinical trials
Butler, M. S. (2008) · Natural Product Reports · doi:10.1039/b514294f · Cited by 1,075
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032
Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy
Kang, M. H., & Reynolds, C. P. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0144 · Cited by 1,016
Metadata
- Authors
- Nguyen, M., Marcellus, R. C., Roulston, A., Watson, M., Serfass, L., Murthy Madiraju, S. R., Goulet, D., Viallet, J., Bélec, L., Billot, X., Acoca, S., Purisima, E., Wiegmans, A., Cluse, L., Johnstone, R. W., Beauparlant, P., & Shore, G. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-12-04
- Volume
- 104
- Issue
- 49
- Pages
- 19512-19517
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1986688227
- Cited by
- 659
- References
- 7
- FWCI
- 16.76
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. https://app.cochat.ai/papers/10.1073/pnas.0709443104
- The paper
- Nguyen, M., Marcellus, R. C., Roulston, A., Watson, M., Serfass, L., Murthy Madiraju, S. R., Goulet, D., Viallet, J., Bélec, L., Billot, X., Acoca, S., Purisima, E., Wiegmans, A., Cluse, L., Johnstone, R. W., Beauparlant, P., & Shore, G. C. (2007). Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0709443104
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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