The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.
The novel BH3 α-helix mimetic JY-1-106 induces apoptosis in a subset of cancer cells (lung cancer, colon cancer and mesothelioma) by disrupting Bcl-xL and Mcl-1 protein–protein interactions with Bak
Open accessAbstract
Background: It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-2/Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. We designed the BH3 α-helix mimetic JY-1-106 to engage the hydrophobic BH3-binding grooves on the surfaces of both Bcl-xL and Mcl-1. Methods: JY-1-106–protein complexes were studied using molecular dynamics (MD) simulations and the SILCS methodology. We have evaluated the in vitro effects of JY-1-106 by using a fluorescence polarization (FP) assay, an XTT assay, apoptosis assays, and immunoprecipitation and western-blot assays. A preclinical human cancer xenograft model was used to test the efficacy of JY-1-106 in vivo. Results: MD and SILCS simulations of the JY-1-106–protein complexes indicated the importance of the aliphatic side chains of JY-1-106 to binding and successfully predicted the improved affinity of the ligand for Bcl-xL over Mcl-1. Ligand binding affinities were measured via an FP assay using a fluorescently labeled Bak-BH3 peptide in vitro. Apoptosis induction via JY-1-106 was evidenced by TUNEL assay and PARP cleavage as well as by Bax–Bax dimerization. Release of multi-domain Bak from its inhibitory binding to Bcl-2/Bcl-xL and Mcl-1 using JY-1-106 was detected via immunoprecipitation (IP) western blotting. At the cellular level, we compared the growth proliferation IC 50 s of JY-1-106 and ABT-737 in multiple cancer cell lines with various Bcl-xL and Mcl-1 expression levels. JY-1-106 effectively induced cell death regardless of the Mcl-1 expression level in ABT-737 resistant solid tumor cells, whilst toxicity toward normal human endothelial cells was limited. Furthermore, synergistic effects were observed in A549 cells using a combination of JY-1-106 and multiple chemotherapeutic agents. We also observed that JY-1-106 was a very effective agent in inducing apoptosis in metabolically stressed tumors. Finally, JY-1-106 was evaluated in a tumor-bearing nude mouse model, and was found to effectively repress tumor growth. Strong TUNEL signals in the tumor cells demonstrated the effectiveness of JY-1-106 in this animal model. No significant side effects were observed in mouse organs after multiple injections. Conclusions: Taken together, these observations demonstrate that JY-1-106 is an effective pan-Bcl-2 inhibitor with very promising clinical potential.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Scalable molecular dynamics with NAMD
Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kalé, L., & Schulten, K. (2005) · Journal of Computational Chemistry · doi:10.1002/jcc.20289 · Cited by 16,914
All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins
MacKerell, A. D., Bashford, D., Bellott, M., Dunbrack, R. L., Evanseck, J. D., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., et al. (1998) · The Journal of Physical Chemistry B · doi:10.1021/jp973084f · Cited by 14,429
Self-citationCHARMM: The biomolecular simulation program
Brooks, B. R., Brooks, C. L., MacKerell, A. D., Nilsson, L., Petrella, R. J., Roux, B., Won, Y., Archontis, G., Bartels, C., Boresch, S., et al. (2009) · Journal of Computational Chemistry · doi:10.1002/jcc.21287 · Cited by 9,115
Self-citationVanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S. C., Zhong, S., Shim, J. Y., Darian, E., Guvench, O., Lopes, P. E. M., Vorobyov, I. V., et al. (2009) · Journal of Computational Chemistry · doi:10.1002/jcc.21367 · Cited by 7,637
Self-citationBcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990) · Nature · doi:10.1038/348334a0 · Cited by 3,720
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,407
Structure of Bcl-x L -Bak Peptide Complex: Recognition Between Regulators of Apoptosis
Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E., Eberstadt, M., Yoon, H. S., Shuker, S. B., Chang, B. S., Minn, A. J., et al. (1997) · Science · doi:10.1126/science.275.5302.983 · Cited by 1,476
Yin, X.-M., Oltvai, Z., & Korsmeyer, S. (1994) · Nature · doi:10.1038/369321a0 · Cited by 1,383
Yu, W.-B., He, X., Vanommeslaeghe, K., & MacKerell, A. D. (2012) · Journal of Computational Chemistry · doi:10.1002/jcc.23067 · Cited by 846
Self-citationScalable Molecular Dynamics with NAMD
Kale, L. V., & Bhatele, A. S. (2016) · CRC Press eBooks · doi:10.1201/b16251-15 · Cited by 645
Perciavalle, R. M., Stewart, D. P., Koss, B. S., Lynch, J., Milasta, S., Bathina, M., Temirov, J. P., Harwig, M. C., Pelletier, S. W., Schuetz, J. D., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2488 · Cited by 431
An informatics approach identifying markers of chemosensitivity in human cancer cell lines.
Amundson, S. A., Myers, T. G., Scudiero, D. A., Kitada, S., Reed, J. C., & Fornace, A. J. (2000) · PubMed · Cited by 399
Alavian, K. N., Li, H., Collis, L. P., Bonanni, L., Zeng, L., Sacchetti, S., Lazrove, E., Nabili, P., Flaherty, B., Graham, M. M., et al. (2011) · Nature Cell Biology · doi:10.1038/ncb2330 · Cited by 295
Computational Fragment-Based Binding Site Identification by Ligand Competitive Saturation
Guvench, O., & MacKerell, A. D. (2009) · PLoS Comput. Biol. · doi:10.1371/journal.pcbi.1000435 · Cited by 243
Self-citationDay, C. L., Smits, C., Fan, F. C., Lee, E. F., Fairlie, W. D., & Hinds, M. G. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.05.071 · Cited by 204
Cell metabolism: An essential link between cell growth and apoptosis
Mason, E. F., & Rathmell, J. C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.08.011 · Cited by 192
Feng, W., Huang, S., Wu, H., & Zhang, M. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.069 · Cited by 184
Mohammad, R. M., Goustin, A. S., Aboukameel, A., Chen, B., Banerjee, S., Wang, G., Nikolovska‐Coleska, Z., Wang, S., & Al-Katib, A. M. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1574 · Cited by 152
Kütük, Ö., & Letai, A. G. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1418 · Cited by 141
Raman, E. P., Yu, W.-B., Guvench, O., & MacKerell, A. D. (2011) · Journal of Chemical Information and Modeling · doi:10.1021/ci100462t · Cited by 126
Self-citationKazi, A., Sun, J., Doi, K., Sung, S., Takahashi, Y., Yin, H. H., Rodriguez, J. M., Becerril, J., Berndt, N., Hamilton, A. D., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.203638 · Cited by 125
Navitoclax (ABT-263) Reduces Bcl-xL–Mediated Chemoresistance in Ovarian Cancer Models
Wong, M., Tan, N., Zha, J., Peale, F. V., Jr., Peng, Y., Fairbrother, W. J., & Belmont, L. D. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0693 · Cited by 115
The Role of BH3-Only Proteins in Tumor Cell Development, Signaling, and Treatment
Elkholi, R., Floros, K. V., & Chipuk, J. E. (2011) · Genes & Cancer · doi:10.1177/1947601911417177 · Cited by 114
Emerging Bcl-2 inhibitors for the treatment of cancer
Azmi, A. S., Wang, Z. P., Philip, P. A., Mohammad, R. M., & Sarkar, F. H. (2010) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2010.515210 · Cited by 105
The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition
Peddaboina, C. S., Jupiter, D. C., Fletcher, S., Yap, J. L., Rai, A., Tobin, R. P., Jiang, W., Rascoe, P. A., Rogers, M. K. N., Smythe, W. R., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-541 · Cited by 78
Self-citationYap, J. L., Cao, X. X., Vanommeslaeghe, K., Jung, K., Peddaboina, C. S., Wilder, P. T., Nan, A., MacKerell, A. D., Smythe, W. R., & Fletcher, S. (2012) · Organic & Biomolecular Chemistry · doi:10.1039/c2ob07125h · Cited by 62
Self-citationCossu, A., Posadino, A. M., Giordo, R., Emanueli, C., Sanguinetti, A. M., Piscopo, A., Poiana, M., Capobianco, G., Piga, A., & Pintus, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048817 · Cited by 61
Chen, J., Zhou, H., Aguilar, A., Liu, L., Bai, L., McEachern, D., Yang, C., Meagher, J. L., Stuckey, J. A., & Wang, S. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3010306 · Cited by 58
Molecular pathogenesis of malignant mesothelioma
Rascoe, P. A., Jupiter, D. C., Cao, X. X., Littlejohn, J., & Smythe, W. R. (2012) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2012.6 · Cited by 46
Self-citationYang, C., & Wang, S. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml200301w · Cited by 37
Small Molecule Inhibitors of Bcl-2 Family Proteins for Pancreatic Cancer Therapy
Masood, A., Azmi, A. S., & Mohammad, R. M. (2011) · Cancers · doi:10.3390/cancers3021527 · Cited by 35
Site-Specific Fragment Identification Guided by Single-Step Free Energy Perturbation Calculations
Raman, E. P., Vanommeslaeghe, K., & MacKerell, A. D. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300088r · Cited by 29
Self-citationHawley, R. G., Chen, Y., Riz, I., & Zeng, C. (2012) · The Open Biology Journal · doi:10.2174/1874196701205010006 · Cited by 14
Identification of Small Molecules Affecting p53-MDM2/MDMX Interaction by Fluorescence Polarization
Zhang, Q., & Lu, H. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-236-0_8 · Cited by 7
Flagged first, then by citations
1 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Pelay‐Gimeno, M., Glas, A., Koch, O., & Grossmann, T. N. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201412070 · Cited by 738
Modulators of Protein–Protein Interactions
Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497
Mitochondria-mediated apoptosis in mammals
Xiong, S., Mu, T., Wang, G., & Jiang, X. (2014) · Protein & Cell · doi:10.1007/s13238-014-0089-1 · Cited by 409
Physiological and Pharmacological Control of BAK, BAX, and Beyond
Luna-Vargas, M. P. A., & Chipuk, J. E. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.07.002 · Cited by 142
Targeting BCL2-Proteins for the Treatment of Solid Tumours
Vogler, M. (2014) · Advances in Medicine · doi:10.1155/2014/943648 · Cited by 121
New dimension in therapeutic targeting of BCL-2 family proteins
Besbes, S., Mirshahi, M., Pocard, M. D., & Billard, C. (2015) · Oncotarget · doi:10.18632/oncotarget.3868 · Cited by 103
Yap, J. L., Chen, L., Lanning, M. E., & Fletcher, S. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01888 · Cited by 99
Self-citationSelective and Potent Proteomimetic Inhibitors of Intracellular Protein–Protein Interactions
Barnard, A., Long, K., Martin, H. L., Miles, J. A., Edwards, T. A., Tomlinson, D. C., Macdonald, A., & Wilson, A. J. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201410810 · Cited by 98
Development of Mcl-1 inhibitors for cancer therapy
Negi, A., & Murphy, P. V. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113038 · Cited by 96
Perturbation of the c-Myc–Max Protein–Protein Interaction via Synthetic α-Helix Mimetics
Jung, K., Wang, H., Teriete, P., Yap, J. L., Chen, L., Lanning, M. E., Hu, A., Lambert, L. J., Holien, T., Sundan, A., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501440q · Cited by 94
Self-citationPelay‐Gimeno, M., Glas, A., Koch, O., & Grossmann, T. N. (2015) · Angewandte Chemie · doi:10.1002/ange.201412070 · Cited by 90
Yu, W., Lakkaraju, S. K., Raman, E. P., Fang, L., & MacKerell, A. D. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/ci500691p · Cited by 90
Self-citationPeptidomimetics: A Synthetic Tool for Inhibiting Protein–Protein Interactions in Cancer
Mabonga, L., & Kappo, A. P. (2019) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-019-09831-5 · Cited by 80
Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer
Haynes, J., & Manogaran, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26051988 · Cited by 82
“For example, drugs targeting the BCL-2 family of proteins, such as BH3 mimetics, have been investigated for their ability to induce apoptosis in CRC cells [142,143].”
Site-Identification by Ligand Competitive Saturation (SILCS) assisted pharmacophore modeling
Yu, W., Lakkaraju, S. K., Raman, E. P., & MacKerell, A. D. (2014) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-014-9728-0 · Cited by 72
Self-citationNegi, A., & Voisin‐Chiret, A. S. (2022) · ChemBioChem · doi:10.1002/cbic.202100689 · Cited by 68
Lakkaraju, S. K., Yu, W., Raman, E. P., Hershfeld, A. V., Fang, L., Deshpande, D. A., & MacKerell, A. D. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/ci500729k · Cited by 66
Self-citationLi, X., Zhang, C., Zhang, X., Wang, S., Meng, Q., Wu, S., Yang, H., Xia, Y., & Chen, R. (2015) · Particle and Fibre Toxicology · doi:10.1186/s12989-016-0115-y · Cited by 62
The role of key genes and pathways involved in the tumorigenesis of Malignant Mesothelioma
de Assis, L. V. M., Locatelli, J., & Isoldi, M. C. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.01.008 · Cited by 59
Dual-Targeted Cascade-Responsive Prodrug Micelle System for Tumor Therapy in Vivo
Dai, L., Cai, R., Li, M., Luo, Z. Y., Yu, Y., Chen, W., Shen, X., Pei, Y., Zhao, X., & Cai, K. (2017) · Chemistry of Materials · doi:10.1021/acs.chemmater.7b02513 · Cited by 58
Yu, W., Raman, E. P., Lakkaraju, S. K., Fang, L., & MacKerell, A. D. (2015) · Biophysical Journal · doi:10.1016/j.bpj.2014.11.095 · Cited by 52
Self-citationMcl-1 inhibitors: a patent review
Chen, L., & Fletcher, S. (2016) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1249848 · Cited by 51
Self-citationLanning, M. E., Yu, W., Yap, J. L., Chauhan, J., Chen, L., Whiting, E., Pidugu, L. S. M., Atkinson, T., Bailey, H., Li, W., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.02.006 · Cited by 50
Self-citationNatural polyphenolic inhibitors against the antiapoptotic BCL-2
Verma, S., Singh, A. P., Kumari, A., Tyagi, C., Goyal, S., Jamal, S., & Grover, A. (2017) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2017.1298129 · Cited by 46
Poustforoosh, A., Faramarz, S., Nematollahi, M. H., Hashemipour, H., Negahdaripour, M., & Pardakhty, A. (2022) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2022.105632 · Cited by 43
Moon, H., & Lim, H. (2014) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2014.10.023 · Cited by 42
Chen, L., Wilder, P. T., Drennen, B., Tran, J., Roth, B. M., Chesko, K. L., Shapiro, P. S., & Fletcher, S. (2015) · Organic & Biomolecular Chemistry · doi:10.1039/c5ob02063h · Cited by 42
Self-citationJo, S., Xu, A. Y., Curtis, J. E., Somani, S., & MacKerell, A. D. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00775 · Cited by 40
Self-citationFrom Concepts to Inhibitors: A Blueprint for Targeting Protein–Protein Interactions
Hong, S. H., Nguyễn, T. T., Ongkingco, J. F., Nazzaro, A., & Arora, P. S. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00046 · Cited by 45
The chemical biology of apoptosis: Revisited after 17 years
Yang, S., Mao, Y., Zhang, H., Xu, Y., An, J., & Huang, Z. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.019 · Cited by 35
Hua, L., Wang, D., Wang, K., Wang, Y., Gu, J., Zhang, Q., You, Q., & Wang, L. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00881 · Cited by 33
Raman, E. P., Lakkaraju, S. K., Denny, R. A., & MacKerell, A. D. (2016) · Journal of Computational Chemistry · doi:10.1002/jcc.24522 · Cited by 33
Self-citationHelix mimetics: Recent developments
Wilson, A. J. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.05.001 · Cited by 32
Drennen, B., Scheenstra, J. A., Yap, J. L., Chen, L., Lanning, M. E., Roth, B. M., Wilder, P. T., & Fletcher, S. (2016) · ChemMedChem · doi:10.1002/cmdc.201500461 · Cited by 30
Self-citationWhiting, E., Lanning, M. E., Scheenstra, J. A., & Fletcher, S. (2014) · The Journal of Organic Chemistry · doi:10.1021/jo502396u · Cited by 28
Self-citationSomani, S., Jo, S., Thirumangalathu, R., Rodrigues, D., Tanenbaum, L. M., Amin, K., MacKerell, A. D., & Thakkar, S. V. (2020) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.10.051 · Cited by 26
Self-citationHIV Protease-Generated Casp8p41, When Bound and Inactivated by Bcl2, Is Degraded by the Proteasome
Natesampillai, S., Cummins, N. W., Nie, Z., Sampath, R., Baker, J. V., Henry, K., Pinzone, M. R., O’Doherty, U., Polley, E. C., Bren, G. D., et al. (2018) · Journal of Virology · doi:10.1128/jvi.00037-18 · Cited by 25
Ludwig, L. M., Nassin, M. L., Hadji, A., & LaBelle, J. L. (2016) · Frontiers in Pediatrics · doi:10.3389/fped.2016.00135 · Cited by 25
Selective and Potent Proteomimetic Inhibitors of Intracellular Protein–Protein Interactions
Barnard, A., Long, K., Martin, H. L., Miles, J. A., Edwards, T. A., Tomlinson, D. C., Macdonald, A., & Wilson, A. J. (2015) · Angewandte Chemie · doi:10.1002/ange.201410810 · Cited by 26
Jackson, M. R., Ashton, M., Koessinger, A. L., Dick, C., Verheij, M., & Chalmers, A. J. (2019) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2019.11.029 · Cited by 24
The disruption of protein-protein interactions as a therapeutic strategy for prostate cancer
Matos, B., Howl, J., Jerónimo, C., & Fardilha, M. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105145 · Cited by 26
Vasudevan, S., Mary, P. V., Vijayakumar, S., & Shankar, R. (2020) · Biophysical Chemistry · doi:10.1016/j.bpc.2020.106394 · Cited by 23
Gowthaman, R., Miller, S. A., Rogers, S. A., Khowsathit, J., Lan, L., Bai, N., Johnson, D. K., Liu, C., Xu, L., Anbanandam, A., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00150 · Cited by 23
Malignant pleural mesothelioma co-opts BCL-XL and autophagy to escape apoptosis
Xu, D., Liang, S., Zhang, Y., Yang, H., Bruggmann, R., Oberhaensli, S., Berezowska, S., Marti, T. M., Hall, S. R. R., Dorn, P., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03668-x · Cited by 24
Lanning, M. E., & Fletcher, S. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.176 · Cited by 19
Self-citationDrennen, B., Goodis, C. C., Bowen, N. G., Yu, W., Vickers, G. E. A., Wilder, P. T., MacKerell, A. D., & Fletcher, S. (2022) · RSC Medicinal Chemistry · doi:10.1039/d2md00095d · Cited by 20
Self-citationNifoussi, S. K., Ratcliffe, N. R., Ornstein, D. L., Kasof, G. M., Strack, S., & Craig, R. W. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.587873 · Cited by 20
Lee, J. H., Oh, M., Kim, H. S., Lee, H., Im, W., & Lim, H. (2015) · ACS Combinatorial Science · doi:10.1021/acscombsci.5b00080 · Cited by 20
Arulananda, S., Lee, E. F., Fairlie, W. D., & John, T. (2020) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2021.1856660 · Cited by 19
Verma, S., Singh, A., & Mishra, A. (2014) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2014.931823 · Cited by 19
Hoda, M. A., Pirker, C., Dong, Y., Schelch, K., Heffeter, P., Kryeziu, K., van Schoonhoven, S., Klikovits, T., László, V., Rózsás, A., et al. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0846 · Cited by 18
Lin, J. J., Qi, W., Chen, K., Yan, Y., Li, X., Feng, Z., & Pan, X. (2018) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22265 · Cited by 18
Small molecules targeting Mcl-1: the search for a silver bullet in cancer therapy
Nhu, D., Lessène, G., Huang, D. C. S., & Burns, C. J. (2016) · MedChemComm · doi:10.1039/c5md00582e · Cited by 16
Lanning, M. E., Wilder, P. T., Bailey, H., Drennen, B., Cavalier, M. C., Chen, L., Yap, J. L., Raje, M. R., & Fletcher, S. (2015) · Organic & Biomolecular Chemistry · doi:10.1039/c5ob00478k · Cited by 16
Self-citationThe first MCL-1-selective BH3 mimetics have therapeutic potential for chronic lymphocytic leukemia
Besbes, S., Pocard, M. D., Mirshahi, M., & Billard, C. (2016) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2016.02.003 · Cited by 18
Recent applications of covalent chemistries in protein–protein interaction inhibitors
Chan, A. M., Goodis, C. C., Pommier, E. G., & Fletcher, S. (2022) · RSC Medicinal Chemistry · doi:10.1039/d2md00112h · Cited by 17
Self-citationWang, T., Yang, Z., Zhang, Y., Zhang, X., Wang, L., Zhang, S., & Jia, L. (2017) · APOPTOSIS · doi:10.1007/s10495-017-1436-5 · Cited by 15
Kim, S., Park, H.-S., & Oh, B. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.06.021 · Cited by 15
Multi-Facial, Non-Peptidic α-Helix Mimetics
Lanning, M. E., & Fletcher, S. (2015) · Biology · doi:10.3390/biology4030540 · Cited by 14
Self-citationXu, D., Yang, H., Schmid, R. A., & Peng, R. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.579464 · Cited by 14
Fu, Z., Du, H., Meng, S., Yao, M., Zhao, P., Li, X., Zheng, X., Zhang, Y., Yang, H., Cai, K., et al. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100449 · Cited by 13
BCL-xL/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells
Perri, M., Yap, J. L., Yu, J., Cione, E., Fletcher, S., & Kane, M. A. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.07.024 · Cited by 12
Self-citationCavalier, M. C., Melville, Z., Aligholizadeh, E., Raman, E. P., Yu, W., Fang, L., Alasady, M. J., Pierce, A. D., Wilder, P. T., MacKerell, A. D., et al. (2016) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798316005532 · Cited by 11
Self-citationExploiting the Biginelli reaction: nitrogen-rich pyrimidine-based tercyclic α-helix mimetics
Lim, Z., Duggan, P. J., Wan, S. S., Lessène, G., Meyer, A. G., & Tuck, K. L. (2015) · Tetrahedron · doi:10.1016/j.tet.2015.12.044 · Cited by 10
Strategies targeting apoptosis proteins to improve therapy of chronic lymphocytic leukemia
Besbes, S., Mirshahi, M., Pocard, M. D., & Billard, C. (2015) · Blood Reviews · doi:10.1016/j.blre.2015.03.005 · Cited by 10
Goodis, C. C., Eberly, C. L., Chan, A. M., Kim, M., Lowe, B. D., Civin, C. I., & Fletcher, S. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.117190 · Cited by 8
Self-citationPerri, M., Yap, J. L., Fletcher, S., Cione, E., & Kane, M. A. (2018) · Oncology Letters · doi:10.3892/ol.2018.8258 · Cited by 7
Self-citationVo, D. D., Gautier, F., Barillé‐Nion, S., Juin, P. P., Levoin, N., & Gree, R. L. (2013) · Tetrahedron · doi:10.1016/j.tet.2013.11.060 · Cited by 7
Dissecting the In Vivo Leukemogenic Potency of Bclxl
Scherzer, K. S. M. T. (2014) · Journal of Leukemia · doi:10.4172/2329-6917.1000158 · Cited by 7
Wang, Z., & Ji, H. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01324 · Cited by 7
Marimuthu, P., & Singaravelu, K. (2018) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2018.1474805 · Cited by 6
Meryet‐Figuière, M., Lecerf, C., Varin, E., Coll, J., Louis, M.-H., Dutoit, S., Giffard, F., Blanc‐Fournier, C., Hedir, S., Vigneron, N., et al. (2017) · Oncology Reports · doi:10.3892/or.2017.5882 · Cited by 6
Chan, A. M., Eberly, C. L., Drennen, B., Goodis, C. C., Wuyts, Z., Civin, C. I., & Fletcher, S. (2025) · Drug Development Research · doi:10.1002/ddr.70084 · Cited by 5
Self-citationNew Entrants into Clinical Trials for Targeted Therapy of Breast Cancer: An Insight
Verma, P., Mittal, P., Singh, A. K., & Singh, I. K. (2019) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520619666191018172926 · Cited by 5
Hart, L. R., Mitchell, S. M., McCallum, P. A., Daso, R. E., & Banerjee, I. A. (2021) · Soft Materials · doi:10.1080/1539445x.2021.1926282 · Cited by 4
Marimuthu, P., Razzokov, J., Singaravelu, K., & Bogaerts, A. (2020) · Biomolecules · doi:10.3390/biom10081114 · Cited by 4
Johnson, E. M., Jayabalan, R., Patra, S. K., & Suh, J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.05.539559 · Cited by 4
The Bak core dimer focuses triacylglycerides in the membrane
Smith, N. A., Wardak, A. Z., Cowan, A. D., Colman, P. M., Czabotar, P. E., & Smith, B. J. (2021) · Biophysical Journal · doi:10.1016/j.bpj.2021.12.043 · Cited by 3
Singaravelu, K., Balasubramanian, P. K., & Marimuthu, P. (2019) · Processes · doi:10.3390/pr7040224 · Cited by 3
Expedient access to pre-organized α-helix mimetics based on an isocinchomeronic acid core
Drennen, B., MacKerell, A. D., & Fletcher, S. (2015) · Tetrahedron Letters · doi:10.1016/j.tetlet.2015.10.020 · Cited by 1
Self-citationBillard, C. (2014) · International Journal of Hematologic Oncology · doi:10.2217/ijh.14.13 · Cited by 1
Oligooxopiperazines as Topographical Helix Mimetics
Lao, B. B., & Arora, P. S. (2016) · Topics in heterocyclic chemistry · doi:10.1007/7081_2015_195 · Cited by 1
Chura‐Chambi, R. M., Arcuri, H. A., Lino, F. S. D. O., Versati, N., Palma, M. S., Favaro, D. C., & Morganti, L. (2016) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.1503
Cane Toad Skin Extracts as Anti-Inflammatory and Anti-Cancer Agents
Qi, J. (2016) · Griffith Research Online · doi:10.25904/1912/3403
Molecular Designing of Small-Molecule Inhibitors for Apoptosis Regulation
Yoshimori, A., & Tanuma, S. (2017) · Current human cell research and applications · doi:10.1007/978-981-10-7296-3_10
Yang, X., Ma, D., Sheng, E., Tang, Y., Tang, Y., Hu, L., Li, S., & Zhu, D. (2022) · Research Square · doi:10.21203/rs.3.rs-2274069/v1
BindingDB (2020) · UC San Diego · doi:10.7270/q2w3809s
BindingDB Entry 50009085: The chemical biology of apoptosis: Revisited after 17 years.
BindingDB (2021) · UC San Diego · doi:10.7270/q2r78jmk
BindingDB (2026) · UC San Diego · doi:10.7270/q2d50sw7
BindingDB (2024) · UC San Diego · doi:10.7270/q2668jc4
Metadata
- Authors
- Cao, X., Yap, J. L., Newell-Rogers, M. K., Peddaboina, C., Jiang, W., Papaconstantinou, H. T., Jupitor, D., Rai, A., Jung, K.-Y., Tubin, R. P., Yu, W., Vanommeslaeghe, K., Wilder, P. T., MacKerell, A. D., Fletcher, S., & Smythe, R. W.
- Affiliations
- Texas A&M University System (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Smythe, Roy W
- ORCID
- Venue
- Molecular Cancer
- Published
- 2013-05-16
- Volume
- 12
- Issue
- 1
- Pages
- 42-42
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC3663763
- OpenAlex
- W2113703332
- Cited by
- 87
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 14 · 2015: 19 · 2014: 12 · 2013: 2
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Samuel Waxman Cancer Research Foundation
- American Association of Colleges of Pharmacy
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- BH3 mimetics, Bcl-xL, Mcl-1, Bak, apoptosis, Bcl-2 family proteins, lung cancer, colon cancer, mesothelioma, tumor xenografts, combination chemotherapy, drug repurposing, Mcl-1 inhibitors, PARP cleavage, molecular dynamics simulation, SILCS, ligand binding affinity, aliphatic side chains
- MeSH terms
- Animals, Antineoplastic Agents, Benzamides, Colonic Neoplasms, Humans, Lung Neoplasms, Mesothelioma, Apoptosis, Protein Structure, Secondary, Protein Structure, Tertiary, Molecular Mimicry, Xenograft Model Antitumor Assays, Cell Line, Tumor, bcl-2 Homologous Antagonist-Killer Protein, bcl-X Protein, Mice, Molecular Dynamics Simulation, para-Aminobenzoates, Myeloid Cell Leukemia Sequence 1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
