3zln Citations

Structure-guided design of a selective BCL-XL inhibitor.

Abstract

The prosurvival BCL-2 family protein BCL-XL is often overexpressed in solid tumors and renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic responses by inhibiting BCL-XL will most likely have widespread utility in cancer treatment and, instead of inhibiting multiple prosurvival BCL-2 family members, a BCL-XL-selective inhibitor would be expected to minimize the toxicity to normal tissues. We describe the use of a high-throughput screen to discover a new series of small molecules targeting BCL-XL and their structure-guided development by medicinal chemistry. The optimized compound, WEHI-539 (7), has high affinity (subnanomolar) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. WEHI-539 will be an invaluable tool for distinguishing the roles of BCL-XL from those of its prosurvival relatives, both in normal cells and notably in malignant tumor cells, many of which may prove to rely upon BCL-XL for their sustained growth.

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Reviews citing this publication (38)

  1. Bcl-2 inhibitors as anti-cancer therapeutics: The impact of and on calcium signaling. Vervloessem T, Kerkhofs M, La Rovere RM, Sneyers F, Parys JB, Bultynck G. Cell Calcium 70 102-116 (2018)
  2. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Adams JM, Cory S. Cell Death Differ 25 27-36 (2018)
  3. How to unleash mitochondrial apoptotic blockades to kill cancers? Deng J. Acta Pharm Sin B 7 18-26 (2017)
  4. Influenza Virus Infection, Interferon Response, Viral Counter-Response, and Apoptosis. Shim JM, Kim J, Tenson T, Min JY, Kainov DE. Viruses 9 (2017)
  5. Progress in targeting the BCL-2 family of proteins. Garner TP, Lopez A, Reyna DE, Spitz AZ, Gavathiotis E. Curr Opin Chem Biol 39 133-142 (2017)
  6. Targeting intrinsic apoptosis and other forms of cell death by BH3-mimetics in glioblastoma. Karpel-Massler G, Ishida CT, Zhang Y, Halatsch ME, Westhoff MA, Siegelin MD. Expert Opin Drug Discov 12 1031-1040 (2017)
  7. Exploiting the pro-apoptotic function of NOXA as a therapeutic modality in cancer. Guikema JE, Amiot M, Eldering E. Expert Opin Ther Targets 21 767-779 (2017)
  8. Targeting anti-apoptotic BCL2 family proteins in haematological malignancies - from pathogenesis to treatment. Vogler M, Walter HS, Dyer MJS. Br J Haematol 178 364-379 (2017)
  9. Development of venetoclax for therapy of lymphoid malignancies. Zhu H, Almasan A. Drug Des Devel Ther 11 685-694 (2017)
  10. Splicing factors of SR and hnRNP families as regulators of apoptosis in cancer. Kędzierska H, Piekiełko-Witkowska A. Cancer Lett 396 53-65 (2017)
  11. BCL-2: Long and winding path from discovery to therapeutic target. Schenk RL, Strasser A, Dewson G. Biochem Biophys Res Commun 482 459-469 (2017)
  12. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. Nat Rev Drug Discov 16 273-284 (2017)
  13. Therapeutic inhibition of BCL-2 and related family members. Levy MA, Claxton DF. Expert Opin Investig Drugs 26 293-301 (2017)
  14. Pathways and mechanisms of venetoclax resistance. Bose P, Gandhi V, Konopleva M. Leuk Lymphoma 58 1-17 (2017)
  15. Targeting BCL-2 to enhance vulnerability to therapy in estrogen receptor-positive breast cancer. Merino D, Lok SW, Visvader JE, Lindeman GJ. Oncogene 35 1877-1887 (2016)
  16. Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation. Ludwig LM, Nassin ML, Hadji A, LaBelle JL. Front Pediatr 4 135 (2016)
  17. Mitochondrial apoptosis and BH3 mimetics. Dai H, Meng XW, Kaufmann SH. F1000Res 5 2804 (2016)
  18. BCL2 Inhibitors as Anticancer Drugs: A Plethora of Misleading BH3 Mimetics. S Soderquist R, Eastman A. Mol Cancer Ther 15 2011-2017 (2016)
  19. Physiological and Pharmacological Control of BAK, BAX, and Beyond. Luna-Vargas MPA, Chipuk JE. Trends Cell Biol 26 906-917 (2016)
  20. Survival control of malignant lymphocytes by anti-apoptotic MCL-1. Fernández-Marrero Y, Spinner S, Kaufmann T, Jost PJ. Leukemia 30 2152-2159 (2016)
  21. Regulation of platelet lifespan by apoptosis. Lebois M, Josefsson EC. Platelets 27 497-504 (2016)
  22. Targeting Cell Survival Proteins for Cancer Cell Death. Pandey MK, Prasad S, Tyagi AK, Deb L, Huang J, Karelia DN, Amin SG, Aggarwal BB. Pharmaceuticals (Basel) 9 (2016)
  23. Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies. Delbridge AR, Grabow S, Strasser A, Vaux DL. Nat Rev Cancer 16 99-109 (2016)
  24. Attacking cancer's Achilles heel: antagonism of anti-apoptotic BCL-2 family members. Opferman JT. FEBS J 283 2661-2675 (2016)
  25. Lessons from gain- and loss-of-function models of pro-survival Bcl2 family proteins: implications for targeted therapy. Sochalska M, Tuzlak S, Egle A, Villunger A. FEBS J 282 834-849 (2015)
  26. New dimension in therapeutic targeting of BCL-2 family proteins. Besbes S, Mirshahi M, Pocard M, Billard C. Oncotarget 6 12862-12871 (2015)
  27. Mitigating risk in academic preclinical drug discovery. Dahlin JL, Inglese J, Walters MA. Nat Rev Drug Discov 14 279-294 (2015)
  28. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Siddiqui WA, Ahad A, Ahsan H. Arch Toxicol 89 289-317 (2015)
  29. Targeting apoptosis pathways for new cancer therapeutics. Bai L, Wang S. Annu Rev Med 65 139-155 (2014)
  30. Targeting BCL2-Proteins for the Treatment of Solid Tumours. Vogler M. Adv Med 2014 943648 (2014)
  31. Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy? Elkholi R, Renault TT, Serasinghe MN, Chipuk JE. Cancer Metab 2 16 (2014)
  32. The essential roles of chemistry in high-throughput screening triage. Dahlin JL, Walters MA. Future Med Chem 6 1265-1290 (2014)
  33. Many players in BCL-2 family affairs. Moldoveanu T, Follis AV, Kriwacki RW, Green DR. Trends Biochem Sci 39 101-111 (2014)
  34. Apoptosis in schistosomes: toward novel targets for the treatment of schistosomiasis. Lee EF, Young ND, Lim NT, Gasser RB, Fairlie WD. Trends Parasitol 30 75-84 (2014)
  35. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Czabotar PE, Lessene G, Strasser A, Adams JM. Nat Rev Mol Cell Biol 15 49-63 (2014)
  36. Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity. Jonas EA. Biochim Biophys Acta 1842 1168-1178 (2014)
  37. Decoding and unlocking the BCL-2 dependency of cancer cells. Juin P, Geneste O, Gautier F, Depil S, Campone M. Nat Rev Cancer 13 455-465 (2013)
  38. Drug discovery and human African trypanosomiasis: a disease less neglected? Ferrins L, Rahmani R, Baell JB. Future Med Chem 5 1801-1841 (2013)

Articles citing this publication (72)

  1. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, Krager K, Ponnappan U, Hauer-Jensen M, Meng A, Zhou D. Nat Med 22 78-83 (2016)
  2. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Leverson JD, Zhang H, Chen J, Tahir SK, Phillips DC, Xue J, Nimmer P, Jin S, Smith M, Xiao Y, Kovar P, Tanaka A, Bruncko M, Sheppard GS, Wang L, Gierke S, Kategaya L, Anderson DJ, Wong C, Eastham-Anderson J, Ludlam MJ, Sampath D, Fairbrother WJ, Wertz I, Rosenberg SH, Tse C, Elmore SW, Souers AJ. Cell Death Dis 6 e1590 (2015)
  3. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Leverson JD, Phillips DC, Mitten MJ, Boghaert ER, Diaz D, Tahir SK, Belmont LD, Nimmer P, Xiao Y, Ma XM, Lowes KN, Kovar P, Chen J, Jin S, Smith M, Xue J, Zhang H, Oleksijew A, Magoc TJ, Vaidya KS, Albert DH, Tarrant JM, La N, Wang L, Tao ZF, Wendt MD, Sampath D, Rosenberg SH, Tse C, Huang DC, Fairbrother WJ, Elmore SW, Souers AJ. Sci Transl Med 7 279ra40 (2015)
  4. Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity. Tao ZF, Hasvold L, Wang L, Wang X, Petros AM, Park CH, Boghaert ER, Catron ND, Chen J, Colman PM, Czabotar PE, Deshayes K, Fairbrother WJ, Flygare JA, Hymowitz SG, Jin S, Judge RA, Koehler MF, Kovar PJ, Lessene G, Mitten MJ, Ndubaku CO, Nimmer P, Purkey HE, Oleksijew A, Phillips DC, Sleebs BE, Smith BJ, Smith ML, Tahir SK, Watson KG, Xiao Y, Xue J, Zhang H, Zobel K, Rosenberg SH, Tse C, Leverson JD, Elmore SW, Souers AJ. ACS Med Chem Lett 5 1088-1093 (2014)
  5. The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression. Wang Y, Chen D, Qian H, Tsai YS, Shao S, Liu Q, Dominguez D, Wang Z. Cancer Cell 26 374-389 (2014)
  6. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Colak S, Zimberlin CD, Fessler E, Hogdal L, Prasetyanti PR, Grandela CM, Letai A, Medema JP. Cell Death Differ 21 1170-1177 (2014)
  7. A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells. Procko E, Berguig GY, Shen BW, Song Y, Frayo S, Convertine AJ, Margineantu D, Booth G, Correia BE, Cheng Y, Schief WR, Hockenbery DM, Press OW, Stoddard BL, Stayton PS, Baker D. Cell 157 1644-1656 (2014)
  8. Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway. Roy MJ, Vom A, Czabotar PE, Lessene G. Br J Pharmacol 171 1973-1987 (2014)
  9. Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors. Waibel M, Solomon VS, Knight DA, Ralli RA, Kim SK, Banks KM, Vidacs E, Virely C, Sia KC, Bracken LS, Collins-Underwood R, Drenberg C, Ramsey LB, Meyer SC, Takiguchi M, Dickins RA, Levine R, Ghysdael J, Dawson MA, Lock RB, Mullighan CG, Johnstone RW. Cell Rep 5 1047-1059 (2013)
  10. 3-Substituted-N-(4-hydroxynaphthalen-1-yl)arylsulfonamides as a novel class of selective Mcl-1 inhibitors: structure-based design, synthesis, SAR, and biological evaluation. Abulwerdi FA, Liao C, Mady AS, Gavin J, Shen C, Cierpicki T, Stuckey JA, Showalter HD, Nikolovska-Coleska Z. J Med Chem 57 4111-4133 (2014)
  11. BM-1197: a novel and specific Bcl-2/Bcl-xL inhibitor inducing complete and long-lasting tumor regression in vivo. Bai L, Chen J, McEachern D, Liu L, Zhou H, Aguilar A, Wang S. PLoS One 9 e99404 (2014)
  12. DNMT3A and TET2 compete and cooperate to repress lineage-specific transcription factors in hematopoietic stem cells. Zhang X, Su J, Jeong M, Ko M, Huang Y, Park HJ, Guzman A, Lei Y, Huang YH, Rao A, Li W, Goodell MA. Nat Genet 48 1014-1023 (2016)
  13. Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer. Goodwin CM, Rossanese OW, Olejniczak ET, Fesik SW. Cell Death Differ 22 2098-2106 (2015)
  14. MYC Is a Major Determinant of Mitotic Cell Fate. Topham C, Tighe A, Ly P, Bennett A, Sloss O, Nelson L, Ridgway RA, Huels D, Littler S, Schandl C, Sun Y, Bechi B, Procter DJ, Sansom OJ, Cleveland DW, Taylor SS. Cancer Cell 28 129-140 (2015)
  15. Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy. Mohana-Kumaran N, Hill DS, Allen JD, Haass NK. Pigment Cell Melanoma Res 27 525-539 (2014)
  16. Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based methods and structure-based design. Burke JP, Bian Z, Shaw S, Zhao B, Goodwin CM, Belmar J, Browning CF, Vigil D, Friberg A, Camper DV, Rossanese OW, Lee T, Olejniczak ET, Fesik SW. J Med Chem 58 3794-3805 (2015)
  17. Bcl-2 antagonists kill plasmacytoid dendritic cells from lupus-prone mice and dampen interferon-α production. Zhan Y, Carrington EM, Ko HJ, Vikstrom IB, Oon S, Zhang JG, Vremec D, Brady JL, Bouillet P, Wu L, Huang DC, Wicks IP, Morand EF, Strasser A, Lew AM. Arthritis Rheumatol 67 797-808 (2015)
  18. Screening-based translation of public research encounters painful problems. Baell JB. ACS Med Chem Lett 6 229-234 (2015)
  19. Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells. Carrington EM, Zhang JG, Sutherland RM, Vikstrom IB, Brady JL, Soo P, Vremec D, Allison C, Lee EF, Fairlie WD, Bouillet P, Grabow S, Ottina E, Herold MJ, Pellegrini M, Huang DC, Tarlinton DM, Strasser A, Lew AM, Zhan Y. Proc Natl Acad Sci U S A 112 4044-4049 (2015)
  20. Mito-priming as a method to engineer Bcl-2 addiction. Lopez J, Bessou M, Riley JS, Giampazolias E, Todt F, Rochegüe T, Oberst A, Green DR, Edlich F, Ichim G, Tait SW. Nat Commun 7 10538 (2016)
  21. Orthogonal functionalisation of α-helix mimetics. Barnard A, Long K, Yeo DJ, Miles JA, Azzarito V, Burslem GM, Prabhakaran P, A Edwards T, Wilson AJ. Org Biomol Chem 12 6794-6799 (2014)
  22. Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL. Dutta S, Ryan J, Chen TS, Kougentakis C, Letai A, Keating AE. J Mol Biol 427 1241-1253 (2015)
  23. BCL-2 is dispensable for thrombopoiesis and platelet survival. Debrincat MA, Pleines I, Lebois M, Lane RM, Holmes ML, Corbin J, Vandenberg CJ, Alexander WS, Ng AP, Strasser A, Bouillet P, Sola-Visner M, Kile BT, Josefsson EC. Cell Death Dis 6 e1721 (2015)
  24. Targeted genomic sequencing of follicular dendritic cell sarcoma reveals recurrent alterations in NF-κB regulatory genes. Griffin GK, Sholl LM, Lindeman NI, Fletcher CD, Hornick JL. Mod Pathol 29 67-74 (2016)
  25. Arresting amyloid with coulomb's law: acetylation of ALS-linked SOD1 by aspirin impedes aggregation. Abdolvahabi A, Shi Y, Rhodes NR, Cook NP, Martí AA, Shaw BF. Biophys J 108 1199-1212 (2015)
  26. Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL. Koehler MF, Bergeron P, Choo EF, Lau K, Ndubaku C, Dudley D, Gibbons P, Sleebs BE, Rye CS, Nikolakopoulos G, Bui C, Kulasegaram S, Kersten WJ, Smith BJ, Czabotar PE, Colman PM, Huang DC, Baell JB, Watson KG, Hasvold L, Tao ZF, Wang L, Souers AJ, Elmore SW, Flygare JA, Fairbrother WJ, Lessene G. ACS Med Chem Lett 5 662-667 (2014)
  27. Isochamaejasmin induces apoptosis in leukemia cells through inhibiting Bcl-2 family proteins. Zhang SD, Shan L, Li W, Li HL, Zhang WD. Chin J Nat Med 13 660-666 (2015)
  28. Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin. Baranski Z, de Jong Y, Ilkova T, Peterse EF, Cleton-Jansen AM, van de Water B, Hogendoorn PC, Bovée JV, Danen EH. Oncotarget 6 36113-36125 (2015)
  29. Targeting MCL-1/BCL-XL Forestalls the Acquisition of Resistance to ABT-199 in Acute Myeloid Leukemia. Lin KH, Winter PS, Xie A, Roth C, Martz CA, Stein EM, Anderson GR, Tingley JP, Wood KC. Sci Rep 6 27696 (2016)
  30. Cancer therapeutics: Pulling the plug on BCL-X(L). Jeng PS, Cheng EH. Nat Chem Biol 9 351-352 (2013)
  31. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance. Pécot J, Maillet L, Le Pen J, Vuillier C, Trécesson SC, Fétiveau A, Sarosiek KA, Bock FJ, Braun F, Letai A, Tait SWG, Gautier F, Juin PP. Cell Rep 17 3347-3358 (2016)
  32. MCL-1 is required throughout B-cell development and its loss sensitizes specific B-cell subsets to inhibition of BCL-2 or BCL-XL. Vikström IB, Slomp A, Carrington EM, Moesbergen LM, Chang C, Kelly GL, Glaser SP, Jansen JH, Leusen JH, Strasser A, Huang DC, Lew AM, Peperzak V, Tarlinton DM. Cell Death Dis 7 e2345 (2016)
  33. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Koss B, Ryan J, Budhraja A, Szarama K, Yang X, Bathina M, Cardone MH, Nikolovska-Coleska Z, Letai A, Opferman JT. Oncotarget 7 11500-11511 (2016)
  34. Bh3 induced conformational changes in Bcl-Xl revealed by crystal structure and comparative analysis. Rajan S, Choi M, Baek K, Yoon HS. Proteins 83 1262-1272 (2015)
  35. Orthologous CRISPR-Cas9 enzymes for combinatorial genetic screens. Najm FJ, Strand C, Donovan KF, Hegde M, Sanson KR, Vaimberg EW, Sullender ME, Hartenian E, Kalani Z, Fusi N, Listgarten J, Younger ST, Bernstein BE, Root DE, Doench JG. Nat Biotechnol 36 179-189 (2018)
  36. Functional disparities among BCL-2 members in tonsillar and leukemic B-cell subsets assessed by BH3-mimetic profiling. Peperzak V, Slinger E, Ter Burg J, Eldering E. Cell Death Differ 24 111-119 (2017)
  37. De novo design, synthesis and evaluation of benzylpiperazine derivatives as highly selective binders of Mcl-1. Ding X, Li Y, Lv L, Zhou M, Han L, Zhang Z, Ba Q, Li J, Wang H, Liu H, Wang R. ChemMedChem 8 1986-2014 (2013)
  38. Rapidly inducible Cas9 and DSB-ddPCR to probe editing kinetics. Rose JC, Stephany JJ, Valente WJ, Trevillian BM, Dang HV, Bielas JH, Maly DJ, Fowler DM. Nat Methods 14 891-896 (2017)
  39. Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study. Antony P, Vijayan R. Drug Des Devel Ther 10 1399-1410 (2016)
  40. Selectivity by small-molecule inhibitors of protein interactions can be driven by protein surface fluctuations. Johnson DK, Karanicolas J. PLoS Comput Biol 11 e1004081 (2015)
  41. Development of 3-phenyl-N-(2-(3-phenylureido)ethyl)-thiophene-2-sulfonamide compounds as inhibitors of antiapoptotic Bcl-2 family proteins. Yang C, Chen S, Zhou M, Li Y, Li Y, Zhang Z, Liu Z, Ba Q, Li J, Wang H, Yan X, Ma D, Wang R. ChemMedChem 9 1436-1452 (2014)
  42. Enrichment of druggable conformations from apo protein structures using cosolvent-accelerated molecular dynamics. Kalenkiewicz A, Grant BJ, Yang CY. Biology (Basel) 4 344-366 (2015)
  43. Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity. Park HA, Licznerski P, Mnatsakanyan N, Niu Y, Sacchetti S, Wu J, Polster BM, Alavian KN, Jonas EA. Cell Death Differ 24 1963-1974 (2017)
  44. Allosteric sensitization of proapoptotic BAX. Pritz JR, Wachter F, Lee S, Luccarelli J, Wales TE, Cohen DT, Coote P, Heffron GJ, Engen JR, Massefski W, Walensky LD. Nat Chem Biol 13 961-967 (2017)
  45. Inhibition of Bcl-xL sensitizes cells to mitotic blockers, but not mitotic drivers. Bennett A, Sloss O, Topham C, Nelson L, Tighe A, Taylor SS. Open Biol 6 (2016)
  46. Rise of the selective inhibitors of anti-apoptotic Bcl-2 family proteins. Han L, Wang R. ChemMedChem 8 1437-1440 (2013)
  47. BCL-XL overexpression promotes tumor progression-associated properties. Trisciuoglio D, Tupone MG, Desideri M, Di Martile M, Gabellini C, Buglioni S, Pallocca M, Alessandrini G, D'Aguanno S, Del Bufalo D. Cell Death Dis 8 3216 (2017)
  48. Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma. Mai WX, Gosa L, Daniels VW, Ta L, Tsang JE, Higgins B, Gilmore WB, Bayley NA, Harati MD, Lee JT, Yong WH, Kornblum HI, Bensinger SJ, Mischel PS, Rao PN, Clark PM, Cloughesy TF, Letai A, Nathanson DA. Nat Med 23 1342-1351 (2017)
  49. Identification of novel small molecule Beclin 1 mimetics activating autophagy. Yu J, Lan L, Lewin SJ, Rogers SA, Roy A, Wu X, Gao P, Karanicolas J, Aubé J, Sun B, Xu L. Oncotarget 8 51355-51369 (2017)
  50. Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer. Merino D, Whittle JR, Vaillant F, Serrano A, Gong JN, Giner G, Maragno AL, Chanrion M, Schneider E, Pal B, Li X, Dewson G, Gräsel J, Liu K, Lalaoui N, Segal D, Herold MJ, Huang DCS, Smyth GK, Geneste O, Lessene G, Visvader JE, Lindeman GJ. Sci Transl Med 9 (2017)
  51. Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1. Jenson JM, Ryan JA, Grant RA, Letai A, Keating AE. Elife 6 (2017)
  52. Human Pluripotent Stem Cells and Derived Neuroprogenitors Display Differential Degrees of Susceptibility to BH3 Mimetics ABT-263, WEHI-539 and ABT-199. García CP, Videla Richardson GA, Dimopoulos NA, Fernandez Espinosa DD, Miriuka SG, Sevlever GE, Romorini L, Scassa ME. PLoS One 11 e0152607 (2016)
  53. Benzothiazole hydrazones of furylbenzamides preferentially stabilize c-MYC and c-KIT1 promoter G-quadruplex DNAs. Pany SP, Bommisetti P, Diveshkumar KV, Pradeepkumar PI. Org Biomol Chem 14 5779-5793 (2016)
  54. Pro-apoptotic meiogynin A derivatives that target Bcl-xL and Mcl-1. Desrat S, Pujals A, Colas C, Dardenne J, Gény C, Favre L, Dumontet V, Iorga BI, Litaudon M, Raphaël M, Wiels J, Roussi F. Bioorg Med Chem Lett 24 5086-5088 (2014)
  55. Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells. Levesley J, Steele L, Brüning-Richardson A, Davison A, Zhou J, Ding C, Lawler S, Short SC. Neuro Oncol 20 203-214 (2018)
  56. Interleukin 8 mediates bcl-xL-induced enhancement of human melanoma cell dissemination and angiogenesis in a zebrafish xenograft model. Gabellini C, Gómez-Abenza E, Ibáñez-Molero S, Tupone MG, Pérez-Oliva AB, de Oliveira S, Del Bufalo D, Mulero V. Int J Cancer 142 584-596 (2018)
  57. Rational design and structure-activity relationship studies of quercetin-amino acid hybrids targeting the anti-apoptotic protein Bcl-xL. Kellici TF, Chatziathanasiadou MV, Lee MS, Sayyad N, Geromichalou EG, Vrettos EI, Tsiailanis AD, Chi SW, Geromichalos GD, Mavromoustakos T, Tzakos AG. Org Biomol Chem 15 7956-7976 (2017)
  58. Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA. Subramanian A, Andronache A, Li YC, Wade M. Oncotarget 7 15986-16002 (2016)
  59. Dynamics of the BH3-Only Protein Binding Interface of Bcl-xL. Liu X, Beugelsdijk A, Chen J. Biophys J 109 1049-1057 (2015)
  60. Research Support, Non-U.S. Gov't Targeting cell death pathways with small molecules: playing with life and death at the cellular level to treat diseases. Lessene G. Future Med Chem 7 2099-2102 (2015)
  61. Development of an efficient route toward meiogynin A-inspired dual inhibitors of Bcl-xL and Mcl-1 anti-apoptotic proteins. Desrat S, Remeur C, Roussi F. Org Biomol Chem 13 5520-5531 (2015)
  62. Design, synthesis, and activity evaluation of selective inhibitors of anti-apoptotic Bcl-2 proteins: The effects on the selectivity of the P1 pockets in the active sites. Wang M, Tian W, Wang C, Lu S, Yang C, Wang J, Song Y, Zhou Y, Zhu J, Li Z, Zheng C. Bioorg Med Chem Lett 26 5207-5211 (2016)
  63. Structure of a Myeloid cell leukemia-1 (Mcl-1) inhibitor bound to drug site 3 of Human Serum Albumin. Zhao B, Sensintaffar J, Bian Z, Belmar J, Lee T, Olejniczak ET, Fesik SW. Bioorg Med Chem 25 3087-3092 (2017)
  64. Deciphering the crucial molecular properties of a series of Benzothiazole Hydrazone inhibitors that targets anti-apoptotic Bcl-xL protein. Marimuthu P, Balasubramanian PK, Singaravelu K. J Biomol Struct Dyn 1-14 (2017)
  65. Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins. Bulanova D, Ianevski A, Bugai A, Akimov Y, Kuivanen S, Paavilainen H, Kakkola L, Nandania J, Turunen L, Ohman T, Ala-Hongisto H, Pesonen HM, Kuisma MS, Honkimaa A, Walton EL, Oksenych V, Lorey MB, Guschin D, Shim J, Kim J, Than TT, Chang SY, Hukkanen V, Kulesskiy E, Marjomaki VS, Julkunen I, Nyman TA, Matikainen S, Saarela JS, Sane F, Hober D, Gabriel G, De Brabander JK, Martikainen M, Windisch MP, Min JY, Bruzzone R, Aittokallio T, Vähä-Koskela M, Vapalahti O, Pulk A, Velagapudi V, Kainov DE. Viruses 9 (2017)
  66. BH3 mimetics efficiently induce apoptosis in mouse basophils and mast cells. Reinhart R, Rohner L, Wicki S, Fux M, Kaufmann T. Cell Death Differ 25 204-216 (2018)
  67. Demethylzeylasteral inhibits cell proliferation and induces apoptosis through suppressing MCL1 in melanoma cells. Zhao Y, He J, Li J, Peng X, Wang X, Dong Z, Zhao E, Liu Y, Wu Z, Cui H. Cell Death Dis 8 e3133 (2017)
  68. Reactive Oxygen Species and Oncoprotein Signaling-A Dangerous Liaison. Chong SJF, Lai JXH, Eu JQ, Bellot GL, Pervaiz S. Antioxid Redox Signal (2018)
  69. Systems modeling accurately predicts responses to genotoxic agents and their synergism with BCL-2 inhibitors in triple negative breast cancer cells. Lucantoni F, Lindner AU, O'Donovan N, Düssmann H, Prehn JHM. Cell Death Dis 9 42 (2018)
  70. An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings. Maffucci I, Hu X, Fumagalli V, Contini A. Front Chem 6 43 (2018)
  71. Examining RAS pathway rewiring with a chemically inducible activator of RAS". Rose JC, Dieter EM, Cunningham-Bryant D, Maly DJ. Small GTPases 1-8 (2018)
  72. S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth. Casara P, Davidson J, Claperon A, Le Toumelin-Braizat G, Vogler M, Bruno A, Chanrion M, Lysiak-Auvity G, Le Diguarher T, Starck JB, Chen I, Whitehead N, Graham C, Matassova N, Dokurno P, Pedder C, Wang Y, Qiu S, Girard AM, Schneider E, Gravé F, Studeny A, Guasconi G, Rocchetti F, Maïga S, Henlin JM, Colland F, Kraus-Berthier L, Le Gouill S, Dyer MJS, Hubbard R, Wood M, Amiot M, Cohen GM, Hickman JA, Morris E, Murray J, Geneste O. Oncotarget 9 20075-20088 (2018)