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Discovery of potent and selective benzothiazole hydrazone inhibitors of Bcl-XL.

Sleebs BE, Kersten WJ, Kulasegaram S, Nikolakopoulos G, Hatzis E, Moss RM, Parisot JP, Yang H, Czabotar PE, Fairlie WD, Lee EF, Adams JM, Chen L, van Delft MF, Lowes KN, Wei A, Huang DC, Colman PM, Street IP, Baell JB, Watson K, Lessene G.

J Med Chem. 2013 Jul 11;56(13):5514-40. doi: 10.1021/jm400556w.


Pseudomonas exotoxin A-mediated apoptosis is Bak dependent and preceded by the degradation of Mcl-1.

Du X, Youle RJ, FitzGerald DJ, Pastan I.

Mol Cell Biol. 2010 Jul;30(14):3444-52. doi: 10.1128/MCB.00813-09.


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.

Cao X, Yap JL, Newell-Rogers MK, Peddaboina C, Jiang W, Papaconstantinou HT, Jupitor D, Rai A, Jung KY, Tubin RP, Yu W, Vanommeslaeghe K, Wilder PT, MacKerell AD Jr, Fletcher S, Smythe RW.

Mol Cancer. 2013 May 16;12(1):42. doi: 10.1186/1476-4598-12-42.


Endogenous Bak inhibitors Mcl-1 and Bcl-xL: differential impact on TRAIL resistance in Bax-deficient carcinoma.

Gillissen B, Wendt J, Richter A, Richter A, Müer A, Overkamp T, Gebhardt N, Preissner R, Belka C, Dörken B, Daniel PT.

J Cell Biol. 2010 Mar 22;188(6):851-62. doi: 10.1083/jcb.200912070.


Mcl-1 and Bcl-xL regulate Bak/Bax-dependent apoptosis of the megakaryocytic lineage at multistages.

Kodama T, Hikita H, Kawaguchi T, Shigekawa M, Shimizu S, Hayashi Y, Li W, Miyagi T, Hosui A, Tatsumi T, Kanto T, Hiramatsu N, Kiyomizu K, Tadokoro S, Tomiyama Y, Hayashi N, Takehara T.

Cell Death Differ. 2012 Nov;19(11):1856-69. doi: 10.1038/cdd.2012.88.


Regulation of stress-induced nuclear protein redistribution: a new function of Bax and Bak uncoupled from Bcl-x(L).

Lindenboim L, Blacher E, Borner C, Stein R.

Cell Death Differ. 2010 Feb;17(2):346-59. doi: 10.1038/cdd.2009.145.


Discovery of potent Mcl-1/Bcl-xL dual inhibitors by using a hybridization strategy based on structural analysis of target proteins.

Tanaka Y, Aikawa K, Nishida G, Homma M, Sogabe S, Igaki S, Hayano Y, Sameshima T, Miyahisa I, Kawamoto T, Tawada M, Imai Y, Inazuka M, Cho N, Imaeda Y, Ishikawa T.

J Med Chem. 2013 Dec 12;56(23):9635-45. doi: 10.1021/jm401170c.


Inhibition of the ER Ca2+ pump forces multidrug-resistant cells deficient in Bak and Bax into necrosis.

Janssen K, Horn S, Niemann MT, Daniel PT, Schulze-Osthoff K, Fischer U.

J Cell Sci. 2009 Dec 15;122(Pt 24):4481-91. doi: 10.1242/jcs.055772.


A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo.

Abulwerdi F, Liao C, Liu M, Azmi AS, Aboukameel A, Mady AS, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z.

Mol Cancer Ther. 2014 Mar;13(3):565-75. doi: 10.1158/1535-7163.MCT-12-0767.


Structure-guided design of a selective BCL-X(L) inhibitor.

Lessene G, Czabotar PE, Sleebs BE, Zobel K, Lowes KN, Adams JM, Baell JB, Colman PM, Deshayes K, Fairbrother WJ, Flygare JA, Gibbons P, Kersten WJ, Kulasegaram S, Moss RM, Parisot JP, Smith BJ, Street IP, Yang H, Huang DC, Watson KG.

Nat Chem Biol. 2013 Jun;9(6):390-7. doi: 10.1038/nchembio.1246.


First evidence that oligopyridines, α-helix foldamers, inhibit Mcl-1 and sensitize ovarian carcinoma cells to Bcl-xL-targeting strategies.

Gloaguen C, Voisin-Chiret AS, Sopkova-de Oliveira Santos J, Fogha J, Gautier F, De Giorgi M, Burzicki G, Perato S, Pétigny-Lechartier C, Simonin-Le Jeune K, Brotin E, Goux D, N'Diaye M, Lambert B, Louis MH, Ligat L, Lopez F, Juin P, Bureau R, Rault S, Poulain L.

J Med Chem. 2015 Feb 26;58(4):1644-68. doi: 10.1021/jm500672y.


Indirect effects of Bax and Bak initiate the mitochondrial alterations that lead to cytochrome c release during arsenic trioxide-induced apoptosis.

Nutt LK, Gogvadze V, Uthaisang W, Mirnikjoo B, McConkey DJ, Orrenius S.

Cancer Biol Ther. 2005 Apr;4(4):459-67.


Triggering of apoptosis by Puma is determined by the threshold set by prosurvival Bcl-2 family proteins.

Callus BA, Moujallad DM, Silke J, Gerl R, Jabbour AM, Ekert PG, Vaux DL.

J Mol Biol. 2008 Dec 12;384(2):313-23. doi: 10.1016/j.jmb.2008.09.041.


Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker.

Richard DJ, Lena R, Bannister T, Blake N, Pierceall WE, Carlson NE, Keller CE, Koenig M, He Y, Minond D, Mishra J, Cameron M, Spicer T, Hodder P, Cardone MH.

Bioorg Med Chem. 2013 Nov 1;21(21):6642-9. doi: 10.1016/j.bmc.2013.08.017.


Design, synthesis and evaluation of marinopyrrole derivatives as selective inhibitors of Mcl-1 binding to pro-apoptotic Bim and dual Mcl-1/Bcl-xL inhibitors.

Li R, Cheng C, Balasis ME, Liu Y, Garner TP, Daniel KG, Li J, Qin Y, Gavathiotis E, Sebti SM.

Eur J Med Chem. 2015 Jan 27;90:315-31. doi: 10.1016/j.ejmech.2014.11.035.


The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib.

Hikita H, Takehara T, Shimizu S, Kodama T, Shigekawa M, Iwase K, Hosui A, Miyagi T, Tatsumi T, Ishida H, Li W, Kanto T, Hiramatsu N, Hayashi N.

Hepatology. 2010 Oct;52(4):1310-21. doi: 10.1002/hep.23836.

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