Granted Patent
B2
US 12,529,692 · App. 17/433,970 · Granted Jan 20, 2026
Live cell imaging dynamic BH3 profiling
Inventors:
Anthony Letai (Medfield, MA); Patrick Bhola (Cambridge, MA); Rebecca German (Sandwich, MA)
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Aspects of the application provide methods and compositions for identifying and evaluating putative therapeutic agents for cancer by live cell imaging. Cell samples comprising cancerous cells that have been pre-treated with a test agent are contacted with a BH 3 peptide, and samples are imaged by live cell imaging over a time interval. Methods of the application can be used to determine whether a patient is likely to benefit from treatment with a particular test agent.
Claims (43)
1 . A method of identifying a putative therapeutic agent for treating cancer, the method comprising:
a. providing a test cell portion of a cell population that comprises primary cancerous cells, wherein the test cell portion has been contacted with a test agent;
b. contacting the test cell portion with a BCL-2 homology domain 3 (BH3) peptide;
c. capturing a series of images of the test cell portion over a time interval by live cell imaging;
d. measuring BH3 peptide-induced mitochondrial outer membrane permeabilization (MOMP) in the test cell portion at different time points in the time interval by detecting emission of a potentiometric dye; and
e. comparing BH3 peptide-induced MOMP measured in the test cell portion to BH3 peptide-induced MOMP in a control cell portion of the cell population, wherein the control cell portion has not been contacted with the test agent;
wherein an increase in BH3 peptide-induced MOMP in the test cell portion compared to that in the control cell portion indicates that the test agent is a putative therapeutic agent for treating cancerous cells of the cell population, and no increase in BH3 peptide-induced MOMP in the test cell portion compared to that in the control cell portion indicates that the test agent is not a putative therapeutic agent for treating cancerous cells of the cell population.
2 . The method of any one of the preceding claims , further comprising:
i) providing the control cell portion of the cell population, wherein the control cell portion has not been contacted with the test agent;
ii) contacting the control cell portion with the BH3 peptide;
iii) capturing a series of images of the control cell portion over the time interval by live cell imaging; and
iv) measuring BH3 peptide-induced MOMP in the control cell portion at the different time points based on the captured images.
3 . The method of any one of the preceding claims , wherein the test cell portion is contacted with the BH3 peptide at a first peptide concentration, and the method further comprises contacting the test cell portion with the BH3 peptide at a second increased peptide concentration after measuring BH3 peptide-induced MOMP at the first peptide concentration.
4 . The method of claim 3 , wherein (c) through (e) are performed at the second increased peptide concentration.
5 . The method of claim 1 , wherein the test cell portion and the control cell portion comprise a detectable marker for cancerous cells, and wherein BH3 peptide-induced MOMP is measured only in cells comprising the detectable marker.
6 . The method of claim 5 , wherein the detectable marker is an intracellular tumor marker, an extracellular tumor marker, or a cell surface tumor marker.
7 . The method of claim 6 , further comprising staining the test and control cell portions with an antibody for the detectable marker, and detecting staining for the antibody to identify cancerous cells.
8 . The method of claim 1 , wherein cells of the test and control cell portions are attached to a solid surface.
9 . The method of claim 8 , wherein the attached cells do not exceed 10,000 cells.
10 . The method of claim 9 , wherein the attached cells are present from at least 100 cells and up to 10,000 cells, at least 100 cells and not exceeding 1,000 cells, at least 1,000 cells, at least 1,000 cells and not exceeding 5,000 cells, or at least 5,000 cells.
11 . The method of claim 1 , wherein the cell population is obtained from a core biopsy sample, a primary human tumor sample, or a patient derived xenograft (PDX).
12 . The method of claim 1 , wherein the BH3 peptide is derived from the BH3 domain of a polypeptide selected from the group consisting of BIM (BCL-2 interacting mediator of cell death), BID (BH3 interacting domain death agonist), BAD (BCL-2-associated death promoter), Noxa A, Noxa B, PUMA (p53 up-regulated modulator of apoptosis), BMF (BCL-2-modifying factor), HRK (harakiri), and BIK (BCL-2 interacting killer).
13 . The method of claim 1 , wherein the BH3 peptide is a non-natural BH3 peptide selected from the group consisting of SEQ ID NO 10, SEQ ID NO 11, SEQ ID NO 12 and SEQ ID NO 16.
14 . A method of identifying a putative therapeutic agent for treating cancer, the method comprising:
a. providing a test cell portion of a cell population that comprises primary cancerous cells, wherein the test cell portion has been contacted with a test agent;
b. contacting the test cell portion with a BCL-2 homology domain 3 (BH3 ) peptide;
c. capturing a series of images of the test cell portion over a time interval by live cell imaging;
d. measuring BH3 peptide-induced mitochondrial outer membrane permeabilization (MOMP) in the test cell portion at different time points in the time interval by detecting emission of a potentiometric dye; and
e. comparing BH3 peptide-induced MOMP measured in the test cell portion to BH3 peptide-induced MOMP in a control cell portion of the cell population, wherein the control cell portion has not been contacted with the test agent;
wherein comparing comprises determining a value for delta priming, wherein delta priming is the difference between BH3 peptide-induced MOMP in the test cell portion and BH3 peptide-induced MOMP in the control cell portion; and
wherein an increase in BH3 peptide-induced MOMP in the test cell portion compared to that in the control cell portion indicates that the test agent is a putative therapeutic agent for treating cancerous cells of the cell population, and no increase in BH3 peptide-induced MOMP in the test cell portion compared to that in the control cell portion indicates that the test agent is not a putative therapeutic agent for treating cancerous cells of the cell population.
15 . The method of claim 14 , wherein the value for delta priming is determined at a plurality of the different time points.
16 . The method of claim 14 , wherein the value for delta priming is a peak value that corresponds to a maximum difference in MOMP occurring over the time interval.
17 . The method of claim 14 , wherein the value for delta priming is a peak value that corresponds to a maximum change in MOMP occurring over a portion of the time interval.
18 . The method of claim 14 , further comprising determining a summary value for delta priming that corresponds to overall changes in MOMP occurring over the time interval.
19 . A method of identifying a putative therapeutic agent for treating cancer, the method comprising:
a. providing a test cell portion of a cell population that comprises primary cancerous cells, wherein the test cell portion has been contacted with a test agent;
b. contacting the test cell portion with a BCL-2 homology domain 3 (BH3) peptide and treating it with a reagent for measuring BH3 peptide-induced mitochondrial outer membrane perrneabilization (MOMP);
c. capturing a series of images of the test cell portion over a time interval by live cell imaging;
d. analyzing the captured images to measure BH3 peptide-induced MOMP in the test cell portion at different time points in the time interval, wherein the analysis comprises measuring an increase or decrease in emission over time by the reagent for measuring BH3 peptide-induced MOMP; and
e. comparing BH3 peptide-induced MOMP measured in the test cell portion to BH3 peptide-induced MOMP in a control cell portion of the cell population, wherein the control cell portion has not been contacted with the test agent;
wherein an increase in BH3 peptide-induced MOMP in the test cell portion compared to that in the control cell portion indicates that the test agent is a putative therapeutic agent for treating cancerous cells of the cell population and no increase in BH3 peptide-induced MOMP in the test cell portion compared to that in the control cell portion indicates that the test agent is not a putative therapeutic agent for treating cancerous cells of the cell population.
20 . The method of claim 19 , wherein comparing comprises determining a value for delta priming, wherein delta priming is the difference between BH3 peptide-induced MOMP in the test cell portion and BH3 peptide-induced MOMP in the control cell portion.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 20, 2025
From: LETAI, ANTHONY; BHOLA, PATRICK; GERMAN, REBECCA
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 071172/0388 →
CONFIRMATORY LICENSE
Recorded Dec 12, 2023
From: DANA-FARBER CANCER INST
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065967/0432 →
Continuity (2)
Provisional Application
62810928
· Feb 26, 2019
References Cited (317)
US 4522811A
· Eppstein et al.
· 1985
[cited by applicant]
US 4676980A
· Segal et al.
· 1987
[cited by applicant]
US 4816567A
· Cabilly et al.
· 1989
[cited by applicant]
US 4946778A
· Ladner et al.
· 1990
[cited by applicant]
US 5225539A
· Winter
· 1993
[cited by applicant]
US 5545806A
· Lonberg et al.
· 1996
[cited by applicant]
US 5545807A
· Surani et al.
· 1996
[cited by applicant]
US 5569825A
· Lonberg et al.
· 1996
[cited by applicant]
US 5625126A
· Lonberg et al.
· 1997
[cited by applicant]
US 5633425A
· Lonberg et al.
· 1997
[cited by applicant]
US 5661016A
· Lonberg et al.
· 1997
[cited by applicant]
US 5674980A
· Frankel et al.
· 1997
[cited by applicant]
US 5804604A
· Frankel et al.
· 1998
[cited by applicant]
US 5916771A
· Hori et al.
· 1999
[cited by applicant]
US 5939598A
· Kucherlapati et al.
· 1999
[cited by applicant]
US 5965703A
· Horne et al.
· 1999
[cited by applicant]
US 7064193B1
· Cory et al.
· 2006
[cited by applicant]
US 7714005B2
· Chen et al.
· 2010
[cited by applicant]
US 7868133B2
· Korsmeyer et al.
· 2011
[cited by applicant]
US 8221966B2
· Letai
· 2012
[cited by applicant]
US 8466140B2
· Altieri et al.
· 2013
[cited by applicant]
US 9360473B2
· Cardone
· 2016
[cited by applicant]
US 9540674B2
· Letai
· 2017
[cited by applicant]
US 9856303B2
· Korsmeyer et al.
· 2018
[cited by applicant]
US 9902759B2
· Korsmeyer et al.
· 2018
[cited by applicant]
US 20020115613A1
· Kumar
· 2002
[cited by applicant]
US 20040171809A1
· Korsmeyer et al.
· 2004
[cited by applicant]
US 20070027175A1
· Shaughnessy et al.
· 2007
[cited by applicant]
US 20130122492A1
· Khosravi et al.
· 2013
[cited by applicant]
US 20160178612A1
· Cardone
· 2016
[cited by applicant]
US 20160258933A1
· Letai
· 2016
[cited by applicant]
US 20170160267A9
· Letai
· 2017
[cited by applicant]
US 20180120297A1
· Letai et al.
· 2018
[cited by applicant]
US 20210255167A1
· Letai et al.
· 2021
[cited by applicant]
JP H10510059A
· 1998
[cited by applicant]
JP 2005130867A
· 2005
[cited by applicant]
JP 2005518393A
· 2005
[cited by applicant]
JP 2006520606A
· 2006
[cited by applicant]
JP 2009532033A
· 2009
[cited by applicant]
JP 2009240173A
· 2009
[cited by applicant]
JP 2009542195A
· 2009
[cited by applicant]
JP 2009543044A
· 2009
[cited by applicant]
JP 2011501731A
· 2011
[cited by applicant]
JP 2012529890A
· 2012
[cited by applicant]
JP 201481365A
· 2014
[cited by applicant]
JP 6663852B
· 2020
[cited by applicant]
WO WO9100360A1
· 1991
[cited by applicant]
WO WO9220373A1
· 1992
[cited by applicant]
WO WO9308829A1
· 1993
[cited by applicant]
WO WO9402602A1
· 1994
[cited by applicant]
WO WO9411026A2
· 1994
[cited by applicant]
WO WO9627011A1
· 1996
[cited by applicant]
WO WO9633735A1
· 1996
[cited by applicant]
WO WO9634096A1
· 1996
[cited by applicant]
WO WO9705265A1
· 1997
[cited by applicant]
WO WO9953049A1
· 1999
[cited by applicant]
WO WO0059526A1
· 2000
[cited by applicant]
WO WO0112661A2
· 2001
[cited by applicant]
WO WO0220568A2
· 2002
[cited by applicant]
WO WO03040168A2
· 2003
[cited by applicant]
WO WO2004022580A2
· 2004
[cited by applicant]
WO WO2004058804A1
· 2004
[cited by applicant]
WO WO2005044839A2
· 2005
[cited by applicant]
WO WO2006099667A1
· 2006
[cited by applicant]
WO WO2007123791A2
· 2007
[cited by applicant]
WO WO2007149270A2
· 2007
[cited by applicant]
WO WO2008021484A2
· 2008
[cited by applicant]
WO WO2010147961A1
· 2010
[cited by applicant]
WO WO2013170176A2
· 2013
[cited by applicant]
WO WO2013188978A1
· 2013
[cited by applicant]
WO WO2014047342A1
· 2014
[cited by applicant]
WO WO2015010094A1
· 2015
[cited by applicant]
WO WO2015042249A1
· 2015
[cited by applicant]
WO WO2016176299A1
· 2016
[cited by applicant]
WO WO2016176288A1
· 2016
[cited by examiner]
Buron et al., PLOS One, vol. 5, Issue 3, e9924, Mar. 31, 2020.
[cited by examiner]
Nonnenmacher et al., Metabolic Engineering, 43:147-155, (Year: 2017).
[cited by examiner]
Porporato et al., Cell Research 28:265-280 (Year: 2018).
[cited by examiner]
Supplementary Partial European Search Report for EP03749602.3 mailed Jun. 7, 2006.
[cited by applicant]
Supplementary European Search Report for EP03749602.3 mailed Sep. 28, 2006.
[cited by applicant]
International Search Report for PCT/US2003/028482 mailed Dec. 8, 2005.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2007/008055 mailed Jan. 2, 2008.
[cited by applicant]
International Preliminary Report on Patentability for PCT/U2007/008055 mailed Sep. 30, 2008.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2013/060707 mailed Jan. 9, 2014.
[cited by applicant]
International Preliminary Report on Patentability for PCT/US2013/060707 mailed Apr. 2, 2015.
[cited by applicant]
Extended European Search Report for EP14845952.2 mailed Mar. 27, 2017.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2014/056284 mailed Dec. 31, 2014.
[cited by applicant]
International Preliminary Report on Patentability for PCT/US2014/056284 mailed Mar. 31, 2016.
[cited by applicant]
Extended European Search Report for EP16787039.3 mailed Oct. 4, 2018.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2016/029495 mailed Aug. 5, 2016.
[cited by applicant]
International Preliminary Report on Patentability for PCT/US2016/029495 mailed Nov. 9, 2017.
[cited by applicant]
Extended European Search Report for EP16787045.0 mailed Oct. 4, 2018.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2016/029510 mailed Aug. 12, 2016.
[cited by applicant]
International Preliminary Report on Patentability for PCT/US2016/029510 mailed Nov. 9, 2017.
[cited by applicant]
International Search Report and Written Opinion for PCT/US2020/019999 mailed Aug. 4, 2020.
[cited by applicant]
International Preliminary Report on Patentability for PCT/US2020/019999 mailed Sep. 10, 2021.
[cited by applicant]
Adams, et al., The Bcl-2 Protein Family: Arbiters of Cell Survival. Science. 1998;281(5381):1322-1326.
[cited by applicant]
Ait-Ikhlef et al. The motoneuron degeneration in the wobbler mouse is independent of the overexpression of a Bcl2 transgene in neurons. Neurosci. Lett. 1995;199:163-6.
[cited by applicant]
Akgul et al., In vivo localisation and stability of human Mcl-1 using green fluorescent protein (GFP) fusion proteins. FEBS Lett. Jul. 28, 2000;478(1-2):72-6.
[cited by applicant]
Bae et al., Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. Apoptosis. 2001;6:319-30.
[cited by applicant]
Barretina et al., The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. Mar. 28, 2012;483(7391):603-7. doi: 10.1038/nature11003. Erratum in: Nature. Dec. 13, 2012;492(742…
[cited by applicant]
Bhola et al., Functionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia. J Clin Invest. Oct. 3, 2016;126(10):3827-3836. doi: 10.1172/JCI82908. Epub Sep. 6, 2016. …
[cited by applicant]
Bouillet et al., Proapoptotic Bcl-2 Relative Bim Required for Certain Apoptotic Responses, Leukocyte Homeostatis, and to Preclude Autoimmunity. Science. 1999;286:1735-8.
[cited by applicant]
Boyd et al., Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins. Oncogene. 1995;11:1921-8.
[cited by applicant]
Brady et al., Reflections on a peptide. Nature. 1994;368:692-3.
[cited by applicant]
Brennan et al., Preparation of Bispecific Antibodies by Chemical Recombination of Monoclonal Immunoglobulin G1 Fragments. Science. 1985;229:81.
[cited by applicant]
Buron et al., Use of human cancer cell lines mitochondria to explore the mechanisms of BH3 peptides and ABT-737-induced mitochondrial membrane permeabilization. PLoS One. Mar. 31, 2010;5(3):e9924. doi: 10.1371/journal.p…
[cited by applicant]
Calin et al., A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia. N. Engl. J. Med. 2005;353:1793-801.
[cited by applicant]
Campos et al., Method for monitoring of mitochondrial cytochrome c release during cell death: Immunodetection of cytochrome c by flow cytometry after selective permeabilization of the plasma membrane. Cytometry Part A. …
[cited by applicant]
Caron et al., Engineered Humanized Dimeric Forms of IgG are More Effective Antibiotics. J. Exp. Med. 1992; 176:1191-5.
[cited by applicant]
Cartron et al., The first α Helix of Bax Plays a Necessary Role in Its Ligand-Induced Activation by the BH3-Only Proteins Bid and PUMA. Mol. Cell 2004; 16:807-18.
[cited by applicant]
Certo et al., Mitochondria Primed by Death Signals Determine Cellular Addiction to Antiapoptotic BCL-2 Family Members. Cancer Cell. May 2006;9:351-65.
[cited by applicant]
Chen et al., Caspase cleavage of Bim
[cited by applicant]
Chen et al., Differential Targeting of Prosurvival Bcl-2 Proteins by Their BH3-Only Ligands Allows Complementary Apoptotic Function. Mol. Cell. 2005;17:393-403.
[cited by applicant]
Cheng et al., Bax-independent inhibition of apoptosis by Bcl-X
[cited by applicant]
Cheng et al., BCL-2, BCL-X
[cited by applicant]
Chipuk et al., Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis. Science. 2004;303:1010-4. Abstract.
[cited by applicant]
Chittenden et al., A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995;14(22):5589-96.
[cited by applicant]
Chittenden et al., Induction of apoptosis by the Bcl-2 homologue Bak. Nature. 1995;374(6524):733-6. Abstract.
[cited by applicant]
Chonghaile et al., Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science. Nov. 25, 2011;334(6059):1129-33. doi:10.1126/science.1206727. Epub Oct. 27, 2011.
[cited by applicant]
Cole et al., The EBV-Hybridoma technique and its application to human lung cancer. Monoclonal Antibodies and Cancer Therapy. 1985:77-96.
[cited by applicant]
Cory et al., The Bcl2 Family: Regulators of the Cellular Life-or-Death Switch. Nat. Rev. Cancer. 2002;2(9):647-56. Abstract.
[cited by applicant]
Cosulich et al., Regulation of apoptosis by BH3 domains in a cell-free system. Curr. Biol. 1997;7(12):913-20.
[cited by applicant]
Cote et al., Generation of human monoclonal antibiotics reactive with cellular antigens. Proc. Natl. Acad. Sci. USA. 1983;80:2026-30.
[cited by applicant]
Czabotar et al., Bax Activation by Bim? Cell Death and Differentiation. Sep. 2009;16:1187-91.
[cited by applicant]
Davids et al., BH3 profiling demonstrates that restoration of apoptotic priming contributes to increased sensitivity to PI3K inhibition in stroma-exposed chronic lymphocytic leukemia cells. Blood 118(21);974. Nov. 18, 2…
[cited by applicant]
Davids et al., Targeting the B-cell lymphoma/leukemia 2 family in cancer. J Clin Oncol. Sep. 1, 2012;30(25):3127-35. doi: 10.1200/JCO.2011.37.0981. Epub May 29, 2012.
[cited by applicant]
Degrado, Designs of peptides and proteins. Adv Protein Chem. 1988;39:51-124.
[cited by applicant]
Del Gaizo Moore et al., BH3 profiling—measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Lett. May 28, 2013;332(2):202-5. doi: 10.1016/j.canlet.2011.12.021. Epub …
[cited by applicant]
Deng et al., BH3 Profiling Identifies Three Distinct Classes of Apoptotic Blocks to Predict Response to ABT-737 and Conventional Chemotherapeutic Agents. Cancer Cell. Aug. 2007;12:171-85.
[cited by applicant]
Derenne et al., Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-xL is an essential survival protein of human myeloma cells. Blood. 2002;100:194-9.
[cited by applicant]
Desagher et al., Bid-induced Conformational Change of Bax is Responsible for Mitochondrial Cytochrome c Release during Apoptosis. J. Cell Biol. 1999;144(5):891-901.
[cited by applicant]
Di Lisa et al., Mitochondrial Function and Cell Injury in Single Cardiac Myocytes Exposed to Anoxia and Reoxygenation. Transplant Proc. 1995;27(5):2829-30.
[cited by applicant]
Di Lisa et al., Mitochondrial membrane potential in single living adult rat cardiac myocytes exposed to anoxia or metabolic inhibition. J. Physiol. 1995;486(1):1-13.
[cited by applicant]
Dohner et al., Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia. N. Engl. J. Med. 2000;343:1910-16.
[cited by applicant]
Egle et al., Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc. Natl. Acad. Sci. USA. 2004;101(16):6164-9.
[cited by applicant]
Ellerby, et al., Anti-cancer activity of targeted pro-apoptotic peptides. Nat. Med. 1999;5(9):1032-8.
[cited by applicant]
Elliott et al., Intercellular Trafficking and Protein Delivery by a Herpesvirus Structural Protein. Cell. 1997;88:223-33.
[cited by applicant]
Emerman et al., Effects of defined medium, fetal bovine serum, and human serum on growth and chemosensitivities of human breast cancer cells in primary culture: inference for in vitro assays. In Vitro Cell Dev Biol. Feb…
[cited by applicant]
Eskes et al., Bid Induces the Oligomerization and Insertion of Bax into the Outer Mitochondrial Membrane. Mol. Cell. Biol. 2000;20(3):929-35.
[cited by applicant]
Fanidi et al., Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature. 1992;359:554-6.
[cited by applicant]
Fishwild et al., High-avidity human IgGk monoclonal antibodies from a novel strain of minilocus transgenic mice. Nature Biotechnology. 1996;14:845-51.
[cited by applicant]
Foight et al., Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells. ACS Chem Biol. Sep. 19, 2014;9(9):1962-8. doi: 10.1021/cb500340w. Epub Jul. 23, 2014.
[cited by applicant]
Frankel et al., Activity of synthetic peptides from the Tat protein of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA. 1989;86:7397-401.
[cited by applicant]
Friedman et al., Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. Dec. 2015; 15(12):747-56. doi: 10.1038/nrc4015. Epub Nov. 5, 2015.
[cited by applicant]
Fuchs et al., Pathway for Polyarginine Entry into Mammalian Cells. Biochemistry Mar. 2004;43(9):2438-44.
[cited by applicant]
Futaki et al., Arginine-rich Peptides: An Abundant Source of Membrane-Permeable Peptides Having Potential as Carriers for Intracellular Protein Delivery. J. Biol. Chem. 2001;276(8):5836-40.
[cited by applicant]
Green et al., A matter of life and death. Cancer Cell. 2002;1:19-30.
[cited by applicant]
Green et al., The Pathophysiology of Mitochondrial Cell Death. Science. 2004;305:626-9.
[cited by applicant]
Green, Life, Death, BH3 Profiles, and the Salmon Mousse. Cancer Cell. Aug. 2007;12:97-9.
[cited by applicant]
Griffiths et al., Cell Damage-induced Conformational Changes of the Pro-Apoptotic Protein Bak In Vivo Precede the Onset of Apoptosis. J. Cell Biol. 1999;144(5):903-14.
[cited by applicant]
Gross et al., Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J. 1998;17(14):3878-85.
[cited by applicant]
Grosschedl et al., Introduction of a μ immunoglobulin gene into the mouse germ line: specific expression in lymphoid cells and synthesis of functional antibody. Cell. 1984;38:647-58.
[cited by applicant]
Gruber et al., Efficient Tumor Cell Lysis Mediated by a Bispecific Single Chain Antibody Expressed in
[cited by applicant]
Gul et al., Apoptotic blocks and chemotherapy resistance: strategies to identify Bcl-2 protein signatures. Briefings in Functional Genomics and Proteomics. Jan. 2008;7(1):27-34.
[cited by applicant]
Hanahan et al., Heritable formation of pancreatic β-cell tumors in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature. 1985;315:115-22.
[cited by applicant]
Hanahan et al., The Hallmarks of Cancer. Cell. 2000;100:57-70.
[cited by applicant]
Hans et al., Beta-carbolines induce apoptosis in cultured cerebellar granule neurons via the mitochondrial pathway. Neuropharmacology. Jan. 2005;48(1):105-17.
[cited by applicant]
Harada et al., Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity. Proc. Natl. Acad. Sci. USA. 2004;101(43):15313-7.
[cited by applicant]
Hemann et al., Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature. 2005;436:807-11.
[cited by applicant]
Hemann et al., Suppression of tumorigenesis by the p53 target PUMA. Proc. Natl. Acad. Sci. USA. 2004;101(25):9333-8.
[cited by applicant]
Hengartner et al., C. elegans Cell Survival Gene ced-9 Encodes a functional Homolog of the Mammalian Proto-Oncogene bcl-2. Cell. 1994;76:665-76.
[cited by applicant]
Hermine et al. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 1996;87(1):265-272.
[cited by applicant]
Holinger et al., Bak BH3 Peptides Antagonize Bcl-x. L Function and Induce Apoptosis through Cytochrome c-independent Activation of Caspases. J. Biol. Chem. 1999;274(19):13298-304.
[cited by applicant]
Holliger et al., Diabodies: Small bivalent and bispecific antibody fragments. Proc. Natl. Acad. Sci. USA. 1993;90:6444-8.
[cited by applicant]
Hoogenboom et al., By-passing Immunisation, Human Antibodies from Synthetic Repertoires of Germline VH Gene segments rearranged in Vitro. J. Mol. Biol. 1992;227:381-8.
[cited by applicant]
Hopp et al., Prediction of protein antigenic determinants from amino acid sequences. Proc. Natl. Acad. Sci. USA. 1981;78:3824-8.
[cited by applicant]
Hsu et al., Nonionic Detergents Induce Dimerization among Members of the Bcl-2 Family. J. Biol. Chem. 1997;272(21):13829-34.
[cited by applicant]
Huang et al., BH3-Only Proteins—Essential Initiators of Apoptotic Cell Death. Cell. 2000; 103:839-42.
[cited by applicant]
Huse et al., Generation of a large Combinatorial Library of the Immunoglobulin Repertoire in Phage Lambda. Science. 1989;246:1275-81.
[cited by applicant]
Inohara et al., Harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-XL. Embo J. 1997;16(7):1686-94.
[cited by applicant]
Jackson et al., Heat shock induces the release of fibroblast growth factor 1 from Nih 3T3 cells. Proc. Natl. Acad. Sci. USA. 1992;89:10691-5.
[cited by applicant]
Jameson et al., A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis. Nature. 1994;368:744-6.
[cited by applicant]
Jones et al., Replacing the complementarily-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522-5.
[cited by applicant]
Jonkers et al., Oncogene addiction: Sometimes a temporary slavery. Cancer Cell. 2004;6:535-8.
[cited by applicant]
Kelekar et al., Bad is a BH3 Domain-Containing Protein that Forms an Inactivating Dimer with Bcl-X
[cited by applicant]
Kelekar et al., Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol. 1998;8:324-30.
[cited by applicant]
Kohler et al., Continuous cultures of fused cells secreting anti-body of predefined specificity. Nature. 1975;256:495-7.
[cited by applicant]
Korsmeyer et al., Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death Differ. Dec. 2000;7(12):1166-73.
[cited by applicant]
Kostelny et al., Formation of a Bispecific antibody by the Leucine Zippers. J. Immunol. 1992;148(5):1547-53.
[cited by applicant]
Kozbor et al., The production of monoclonal antibodies from human lymphocytes. Immunol Today. 1983;4:72-9.
[cited by applicant]
Kozbor, A human hybrid Myeloma for production of human monoclonal antibodies. J. Immunol. 1984;133:3001-5.
[cited by applicant]
Krieg, Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides. Biochim Biophys Acta. 1999;1489(1):107-16.
[cited by applicant]
Kuwana et al., BH3 Domains of BH3-Only Proteins Differentially Regulate Bax-Mediated Mitochondrial Membrane Permeabilization Both Directly and Indirectly. Mol. Cell. 2005;17:525-35.
[cited by applicant]
Kuwana et al., Bid, Bax, and Lipids Cooperate to Form Supramolecular Openings in the Outer Mitochondrial Membrane. Cell. 2002;111:331-42.
[cited by applicant]
Kyte et al., A Simple Method for displaying the Hydropathic Character of a protein. J. Mol. Biol. 1982;157:105-42.
[cited by applicant]
La Vieira, et al., Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl-XL. Oncogene. 2002;21(13):1963-77.
[cited by applicant]
Leo et al., Characterization of the Antiapoptotic Bcl-2 Family Member Myeloid Cell Leukemia-1 (Mcl-1) and the Stimulation of Its Message by Gonadotropins in the Rat Ovary. Endocrinol. 1999;140(12):5469-77.
[cited by applicant]
Letai et al., Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell. 2004;6:241-9.
[cited by applicant]
Letai et al., Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. Sep. 2002;2(3):183-92.
[cited by applicant]
Letai, BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics. Expert Opin Biol Ther. Apr. 2003;3(2):293-304.
[cited by applicant]
Letai, Perturbing cancer cell mitochondria to learn how to kill cancer with BH3 profiling. Broad Institute, Seminar Series on Cell Circuits and Epigenomics. Jul. 28, 2014 Presentation.
[cited by applicant]
Letai, The BCL-2 network: Mechanistic insights and therapeutic potential. Drug Disc. Today: Disease Mechanisms. 2005;2(2):145-51.
[cited by applicant]
Li et al., Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis. Cell. 1998;94(4):491-501.
[cited by applicant]
Li et al., Endonuclease G is an apoptotic DNase when released from mitochondria. Nature. 2001;412:95-9.
[cited by applicant]
Li et al., tsg 101: A novel tumor susceptibility gene isolated by controlled Homozygous functional knockout of Allelic Loci in Mammalian Cells. Cell. 1996;85:319-29.
[cited by applicant]
Lieber et al., Apoptosis sensitizers enhance cytotoxicity in hepatoblastoma cells. Pediatr Surg Int. Feb. 2012;28(2):149-59. doi: 10.1007/s00383-011-2988-z.
[cited by applicant]
Liu et al., Bax conformational change is a crucial step for PUMA-mediated apoptosis in human leukemia. Biochem Biophys Res Commun. 2003;310(3):956-62.
[cited by applicant]
Lonberg et al., Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature. 1994;368:856-9.
[cited by applicant]
Lonberg et al., Human Antibodies from Transgenic Mice. Intern Rev Immunol. 1995;13:65-93.
[cited by applicant]
Long et al., Optimization and validation of mitochondria-based functional assay as a useful tool to identify BH3-like molecules selectively targeting anti-apoptotic Bcl-2 proteins. BMC Biotechnol. May 24, 2013;13:45. do…
[cited by applicant]
Luo et al., Bid, a Bc12 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors, Cell. 1998;94(4):481-90.
[cited by applicant]
Lutter et al., The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. BMC Cell Biology. 2001;2:22.
[cited by applicant]
Marani et al., Identification of Novel Isoforms of the BH3 Domain Protein Bim which Directly Activate Bax to Trigger Apoptosis. Mol Cell Biol. 2002;22(11):3577-89.
[cited by applicant]
Marks et al., By-passing Immunization human Antibodies from v-gene libraries displayed on phage. J. Mol. Biol. 1991;222:581.
[cited by applicant]
Marks et al., By-passing immunization: building high affinity human antibodies by chin shuffling. Bio/Technology. 1992;10:779-83.
[cited by applicant]
Martin, Opening the Cellular Poison Cabinet. Science. Dec. 2010;330:1330-1.
[cited by applicant]
Mason et al., The Hypogonadal mouse: reproductive functions restored by gene therapy. Science. 1986;234:1372-8.
[cited by applicant]
Matsushita et al., A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation. J. Neuroscience. 2001;21(16):6000-7.
[cited by applicant]
Matsuzaki, Why and how are peptide-lipid interactions utilized for self-defense? Biochem. Soc. Transactions. 2001;29:598-601.
[cited by applicant]
McDonnell et al., bcl-2-Immunoglobulin Transgenic Mice Demonstrate Extended B Cell Survival and Follicular Lymphoproliferation. Cell. 1989;57:79-88.
[cited by applicant]
Means et al., Modifications to change properties in Chemical Modification of Protein. 1974. Chapter 3, pp. 35-54, Holden-Day.
[cited by applicant]
Milstein et al., Hybrid hybridomas and their use in immunohistochemistry. Nature. 1983;305:537-9.
[cited by applicant]
Montero et al., Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. Feb. 26, 2015;160(5):977-90. doi:10.1016/j.cell.2015.01.042.
[cited by applicant]
Morrison et al., Success in specification. Nature. 1994;368:812-3.
[cited by applicant]
Muchmore et al., X-ray and NMR structure of human Bcl-XL, an inhibitor of programmed cell death. Nature. 1996;381:335-41.
[cited by applicant]
Munson et al., Ligand: A Versatile Computerized Approach for Characterization of Ligand-Binding Systems. Analytical Biochemistry. 1980;107:220-39.
[cited by applicant]
Nakano et al., PUMA, a Novel Proapoptotic Gene, is Induced by p53. Mol. Cell. 2001;7:683-94.
[cited by applicant]
Narita, et al., Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc. Natl. Acad. Sci. USA. 1998;95:14681-6.
[cited by applicant]
Neuberger et al., Generating high-avidity human Mabs in mice. Nature Biotechnology. 1996;14:826.
[cited by applicant]
O'Brien et al., Phase I and II Multicenter Study of Oblimersen Sodium, a Bcl-2 Antisense Oligonucleotide, in Patients With Advanced Chronic Lymphocytic Leukemia. J. Clin. Oncol. 2005;23(30):7697-702.
[cited by applicant]
O'Connor et al., Bim: a novel member of the Bcl-2 family that promotes apoptosis. Embo J. 1998;17(2):384-95.
[cited by applicant]
Oda et al., Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis. Science. 2000;288:1053-8.
[cited by applicant]
Oh et al., Conformational Changes in BID, a Pro-apoptotic BCL-2 Family Member, upon Membrane Binding. J. Biol. Chem. 2005;280(1):753-67.
[cited by applicant]
Oliver et al., Permeabilization of Cell Membranes. C. Oliver and M.C. Jamur (eds.), Immunocytochemical Methods and Protocols, Methods in Molecular Biology, vol. 588, DOI 10.1007/978-1-59745-324-0_9, © Humana Press, a pa…
[cited by applicant]
Oltersdorf et al., An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435:677-81.
[cited by applicant]
Opferman et al., Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003;426:671-6.
[cited by applicant]
Pan et al., Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. Mar. 2014;4(3):362-75. doi: 10.1158/2159-8290.CD-13-0609. Epub Dec. 17, 2013.
[cited by applicant]
Pinkert et al., An albumin enhancer located 10 kb upstream functions along with its promoter to direct efficient, liver-specific expression in transgenic mice. Genes and Dev. 1987;1:268-276.
[cited by applicant]
Polster et al., BH3 Death Domain Peptide Induces Cell Type-selective Mitochondrial Outer Membrane Permeability. J. Biol. Chem. 2001;276 (41):37887-94.
[cited by applicant]
Presta, Antibody engineering. Curr. Op. Struct. Biol. 1992;2:593-6.
[cited by applicant]
Putcha et al., Induction of BIM, a Proapoptotic BH3-Only BCL-2 Family Member, is Critical for Neuronal Apoptosis. Neuron. 2001;29(3):615-28.
[cited by applicant]
Puthalakath et al., Bmf: a Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis. Science. 2001;293:1829-32.
[cited by applicant]
Puthalakath et al., Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ. 2002;9:505-12.
[cited by applicant]
Puthalakath et al., The Proapoptotic Activity of the Bcl-2 Family Member Bim is Regulated by Interaction with the Dynein Motor Complex. Mol. Cell. 1999;3:287-96.
[cited by applicant]
Quinsay et al., Pro-Apoptotic Bnip3 Mediates Permeabilization of Mitochondria and Release of Cytocrome c via a Novel Mechanism. Circulation. Oct. 28, 2008;118(18):S388. Abstract.
[cited by applicant]
Raff, Social controls on cell survival and cell death. Nature. 1992;356:397-400.
[cited by applicant]
Rassenti et al., ZAP-70 Compared with Immunoglobulin Heavy-Chain Gene Mutation Status as a predictor of Disease Progression in Chronic Lymphocytic Leukemia. N. Engl. J. Med. 2004;351:893-901.
[cited by applicant]
Ray et al., BNIP3 Heterodimerizes with Bcl-2/Bcl-X
[cited by applicant]
Readhead et al., Expression of a myelin basic protein gene in transgenic shiverer mice: correction of the dysmyelinating phenotype. Cell. 1987;48:703-12.
[cited by applicant]
Ren et al., BID, BIM, and PUMA are Essential for Activation of the BAX- and BAK-Dependent Cell Death Program. Science. Dec. 2010;330:1390-3.
[cited by applicant]
Riechmann et al., Reshaping human antibodies for therapy. Nature. 1988;332:323-7.
[cited by applicant]
Rizvi et al., Platelet-derived growth factor primes cancer-associated fibroblasts for apoptosis. J Biol Chem. Aug. 15, 2014;289(33):22835-49. doi:10.1074/jbc.M114.563064. Epub Jun. 27, 2014.
[cited by applicant]
Rothbard et al., Conjugation of arginine oligomers to cyclosporine A facilitates topical delivery and inhibition of inflammation. Nature Med. 2000;6(11):1253-7.
[cited by applicant]
Ryan et al., BH3 profiling in whole cells by fluorimeter or FACS. Methods. Jun. 1, 2013;61(2):156-64. doi: 10.1016/j.ymeth.2013.04.006. Epub Apr. 20, 2013.
[cited by applicant]
Ryan et al., Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes. Proc Natl Acad Sci U S A. Jul. 20, 2010;107(29):12895-900. doi: 10.1073/pnas.0914878107. Epub Jul. 6, 20…
[cited by applicant]
Samson et al., A 35 amino acid fragment of leptin inhibits feeding in the rat. Endocrinology. 1996;137:5182-5.
[cited by applicant]
Sattler et al., Structure of Bcl-XL-Bak Peptide Complex: Recognition Between Regulators of Apoptosis. Science. 1997;275:983-6.
[cited by applicant]
Schimmer et al., The BH3 domain of BAD fused to the Antennapedia peptide induces apoptosis via its alpha helical structure and independent of Bcl-2. Cell Death Differ. Jul. 2001;8(7):725-33. doi: 10.1038/sj.cdd.4400870.
[cited by applicant]
Schmitt et al., Genetic analysis of chemoresistance in primary murine lymphomas. Nat Med. 2000;6(9):1029-1035. doi: 10.1038/79542.
[cited by applicant]
Sen et al., Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J Med Microbiol. Sep. 2007;56(Pt 9):1213-8.
[cited by applicant]
Shalaby et al., Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene. Exp. Med. 1992;175:217-25.
[cited by applicant]
Shangary et al., Peptides derived from BH3 domains of Bcl-2 family members: a comparative analysis of inhibition of Bcl-2, Bcl-x(L) and Bax oligomerization, induction of cytochrome c release, and activation of cell deat…
[cited by applicant]
Shimizu et al., Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity. Proc Natl Aca…
[cited by applicant]
Shopes, A genetically engineered human IgG mutant with enhanced cytolytic activity. J Immunol. 1992. 148:2918-2922.
[cited by applicant]
Soltow et al., Overexpression of CuZnSOD or MnSOD protects satellite cells from doxorubicin-induced apoptosis. FASEB Journal. Apr. 2007;21:A449. Abstract.
[cited by applicant]
Song et al., Carbon monoxide promotes Fas/CD95-induced apoptosis in Jurkat cells. J Biol Chem. Oct. 22, 2004;279(43):44327-34. Epub Jul. 27, 2004. Erratum in: J Biol Chem. Jun. 10, 2005;280(23):22555.
[cited by applicant]
Stevenson et al., A chimeric antibody with dual Fc regions (bisFabFc) prepared by manipulations at the IgG hinge. Anti-Cancer Drug Design. 1989;3:219-30.
[cited by applicant]
Strupp et al., Treatment of Cells with Detergent Activates Caspases and Induces Apoptotic Cell Death. J. Membrane Biology. Jun. 2000;175(3): 181-9.
[cited by applicant]
Sugiyama et al., Activation of mitochondrial voltage-dependent anion channel by a pro-apoptotic BH3-only protein Bim. Oncogene. Jul. 25, 2002;21(32):4944-56.
[cited by applicant]
Suresh et al., Bispecific Monoclonal Antibodies from Hybrid Hybridomas. Methods in Enzymology. 1986;121:210-28.
[cited by applicant]
Suzuki et al., Possible Existence of Common Internalization Mechanisms among Arginine-rich Peptides. J. Biol. Chem. 2002;277:2437-43.
[cited by applicant]
Terradillos et al. Direct addition of BimL to mitochondria does not lead to cytochrome c release. FEBS Lett. 2002;522(1-3):29-34.
[cited by applicant]
Traunecker et al., Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells. EMBO J. 1991;10:3655-9.
[cited by applicant]
Tutt et al., Trispecific F(ab')3 derivatives that use cooperative signaling via the TCR/CD3 complex and CD2 to activate and redirect resting cytotoxic T cells. J. Immunol. 1991;147:60.
[cited by applicant]
Vaquero et al., Extracellular matrix proteins protect pancreatic cancer cells from death via mitochondrial and nonmitochondrial pathways. Gastroenterology. Oct. 2003;125(4):1188-202.
[cited by applicant]
Vaux et al., Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988;335(6189):440-42.
[cited by applicant]
Verhoeyen et al., Reshaping Human Antibodies: Grafting an Antilysozyme Activity. Science. 1988;239:1534-6.
[cited by applicant]
Vieira et al., Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl-XL. Oncogene. 2002 21:1963-77.
[cited by applicant]
Vitetta et al., Redesigning Nature's Poisons to Create Anti-Tumor Reagents. Science. 1987;238:1098-104.
[cited by applicant]
Vives et al., A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus. J. Biol. Chem. 1997;272(25):16010-7.
[cited by applicant]
Vo et al., Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell. Oct. 12, 2012;151(2):344-55.
[cited by applicant]
Wang et al., Bid: A Novel BH3 Domain-Only Death Agonist. Genes Dev. 1996;10(22):2859-69.
[cited by applicant]
Wang et al., Cell Permeable Bcl-2 binding Peptides: A Chemical Approach to Apoptosis Induction in Tumor Cells. Cancer Res. 2000;60:1498-502.
[cited by applicant]
Wang et al., Structure based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. PNAS. 2000;97:7124-9.
[cited by applicant]
Wang, The Expanding Role of Mitochondria in Apoptosis. Genes Dev. 2001; 15:2922-33.
[cited by applicant]
Wei et al., Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death. Science. 2001;292(5517):727-30.
[cited by applicant]
Wei et al., tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes & Development. 2000;14:2060-71.
[cited by applicant]
Weinstein, Addiction to Oncogenes—the Achilles Heal of Cancer. Science. 2002;297:63-4.
[cited by applicant]
Werner et al., Bcl-2 Family Member Bfl-1/A1 Sequesters Truncated Bid to Inhibit its Collaboration With Pro-Apoptotic Bak or Bax. J. Biol. Chem. 2002;277(25):22781-8.
[cited by applicant]
Westerhoff et al., Magainins and the disruption of membrane-linked free-energy transduction. Proc. Natl. Acad. Sci. USA. Sep. 1989;86(17):6597-601.
[cited by applicant]
Wilkinson, Immunochemical techniques inspire development of new antibody purification methods. The Scientist. 2000;14(8):25-8.
[cited by applicant]
Willis et al., Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, not Bax or Bak. Science. Feb. 2007;315:856-9.
[cited by applicant]
Willis et al., Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005;19:1294-305.
[cited by applicant]
Wolff et al., Monoclonal antibody homodimers: Enhanced antitumor activity in Nude Mice. Cancer Research. 1993;53:2560-5.
[cited by applicant]
Wolter et al., Movement of Bax from the Cytosol to Mitochondria during Apoptosis. J. Cell Biol. 1997;139(5):1281-92.
[cited by applicant]
Yamaguchi et al., Bcl-XL Protects BimEL-induced Bax Conformational Change and Cytochrome c Release Independent of Interacting with Bax or BimEL. J. Biol. Chem. 2002;277(44):41604-12.
[cited by applicant]
Yang et al., Bad, a Heterodimeric Partner for Bcl-XL and Bcl-2, Displaces Bax and Promotes Cell Death. Cell. 1995;80(2):285-91.
[cited by applicant]
Yang et al., Calculation of Protein Conformation from Circular Dichroism. Methods Enzymol. 1986;130:208-69.
[cited by applicant]
Yasuda et al., BNIP3 α: a Human Homolog of Mitochondrial Proapoptotic protein BNIP3. Cancer Res. 1999;59:533-7.
[cited by applicant]
Yi et al., Inhibition of Bid-induced apoptosis by Bcl-2. tBid insertion, Bax translocation, and Bax/Bak oligomerization suppressed. J Biol Chem. May 9, 2003;278(19):16992-9. Epub Mar. 6, 2003.
[cited by applicant]
Zha et al., BH3 Domain of BAD is Required for Heterodimerization with Bcl-XL and Pro-apoptotic Activity. J. Biol. Chem. 1997;272(39):24101-4.
[cited by applicant]
Zha et al., Posttranslational N-Myristoylation of BID as a Molecular Switch for targeting Mitochondria and Apoptosis. Science. 2000;290(5497)1761-5.
[cited by applicant]
Zha et al., Serine Phosphorylation of Death Agonist BAD in Response to Survival Factor Results in Binding to 14-3-3 Not BCL-XL. Cell. 1996;87:619-28.
[cited by applicant]
Zhou et al., Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. Dec. 24, 2009;462(7276):1070-4.
[cited by applicant]
Zong et al., BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes & Development. 2001;15:1481-6.
[cited by applicant]