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Publications

Download reprints of research and studies we have submitted to scientific and medical journals.
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Farhad Ravandi, Ellen K. Ritchie, Hamid Sayar, Jeffrey E. Lancet, Michael D. Craig, Norbert Vey, Stephen A. Strickland, Gary J. Schiller, Elias Jabbour, Arnaud Pigneux, Heinz-August Horst, Christian Récher, Virginia M. Klimek, Jorge E. Cortes, Angelo-Michele Carella, Miklos Egyed, Utz Krug, Judith A. Fox, Adam R. Craig, Renee Ward, Jennifer A. Smith, Gary Acton, Hagop M. Kantarjian, Robert K. Stuart  Phase 3 Results For Vosaroxin/Cytarabine In The Subset Of Patients ≥60 Years Old With Refractory/Early Relapsed Acute Myeloid Leukemia  Haematologica May 2018 : haematol.2018.191361; Doi:10.3324/haematol.2018.191361

Sedov V, Stuart RK  Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape.  Ther Adv Hematol. 2017 Jun;8(6):185-195. doi: 10.1177/2040620717703012. Epub 2017 Apr 21.

Giovanni Luca Gravina, Andrea Mancini, Claudia Mattei, Flora Vitale, Francesco Marampon, Alessandro Colapietro, Giulia Rossi, Luca Ventura, Antonella Vetuschi, Ernesto Di Cesare, Judith A. Fox, Claudio Festuccia  Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models.  Oncotarget. 2017; 8:29865-29886. doi: 10.18632/oncotarget.16168

Nijenhuis CM, Lucas L, Rosing H, Huitema AD, Mergui-Roelvink , Jamieson GC, Fox JA, Mould DR, Schellens JH, Beijnen JH  Metabolism and disposition of the anticancer quinolone derivative vosaroxin, a novel inhibitor of topoisomerase II.  Invest New Drugs. 2017 Jan 31. doi: 10.1007/s10637-017-0428-1. [Epub ahead of print]

Gene C. Jamieson, Judith A. Fox, Ming Poi, Stephen A. Strickland.  Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic Agent for Acute Myeloid Leukemia.  Drugs. 2016 Sep;76(13):1245-55. doi: 10.1007/s40265-016-0614-z.

F Ravandi, E K Ritchie, H Sayar, JE Lancet, MD Craig, N Vey, SA Strickland, GJ Schiller, E Jabbour, HP Erba, A Pigneux, HA Horst, C Recher, VM Klimek, J Cortes, GJ Roboz, O Odenike, X Thomas, VHavelange, J Maertens, HG Derigs, M Heuser, L Damon, BL Powell, G Gaidano, AM Carella, A Wei, D Hogge, AR Craig, JA Fox, R Ward, JA Smith, G Acton, C Mehta, RK Stuart, HM Kantarjian.  Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.  The Lancet published online: 30 July 2015 (DOI: http://dx.doi.org/10.1016/S1470-2045(15)00201-6)

Anya K Hotinski, Ian D Lewis, David M Ross.  Vosaroxin is a novel topoisomerase-II inhibitor with efficacy in relapsed and refractory acute myeloid leukaemia.  Expert Opinion on Pharmacotherapy, June 2015, Vol. 16, No. 9 : Pages 1395-1402 (doi: 10.1517/14656566.2015.1044437)

Dennis M, Russell N, Hills RK, Hemmaway C, Panoskaltsis N, McMullin MF, Kjeldsen L, Dignum H, Thomas IF, Clark RE, Milligan D, Burnett AK.  Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia.  Expert Opinion on Pharmacotherapy, June 2015, Vol. 16, No. 9 : Pages 1395-1402 (doi: 10.1517/14656566.2015.1044437)

Stuart, R. K., Cripe, L. D., Maris, M. B., Cooper, M. A., Stone, R. M., Dakhil, S. R., Turturro, F., Stock, W., Mason, J., Shami, P. J., Strickland, S. A., Costa, L. J., Borthakur, G., Michelson, G. C., Fox, J. A., Leavitt, R. D. and Ravandi, F.  REVEAL-1, a phase 2 dose regimen optimization study of vosaroxin in older poor-risk patients with previously untreated acute myeloid leukaemia. British Journal of Haematology. doi: 10.1111/bjh.13214.

Jeffrey E. Lancet, Gail J. Roboz, Larry D. Cripe, Glenn C. Michelson, Judith A. Fox, Richard D. Leavitt, Tianling Chen, Rachael Hawtin, Adam R. Craig, Farhad Ravandi, Michael B. Maris, Robert K. Stuart, Judith E. Karp  A phase 1b/2 study of combination vosaroxin and cytarabine in patients with relapsed or refractory acute myeloid leukemia. Haematologica January 2014:doi:10.3324/haematol.2014.114769

Freeman C, Keane N, Swords R, and Giles F.  Vosaroxin: a new valuable tool with the potential to replace anthracyclines in the treatment of AML? Expert Opinion on Pharmacotherapy. 20 May 2013 [Epub ahead of print].

Jonathan A Abbas, Robert K Stuart.  Vosaroxin: a novel antineoplastic quinolone. Expert Opinion on Investigational Drugs Aug 2012, Vol. 21, No. 8, Pages 1223-1233: 1223-1233.

Gordon IK, Graves C, Kil WJ, Meushaw T, Tofilon P, Camphausen K.  Radiosensitization by the novel DNA intercalating agent vosaroxin. Radiat Oncol. 2012;7:26. In press. Provisional pdf available from: http://www.ro-journal.com/content/pdf/1748-717X-7-26.pdf.

Ritchie EK.  New weapons and strategies in the battle against relapsed acute myeloid leukemia (AML). In:Treatment strategies - hematology. Volume 2, Issue 1. Holcroft R, editor. London: The Cambridge Research Centre; 2012. p. 79 84.

JE Lancet, F Ravandi, RM Ricklis, LD Cripe, HM Kantarjian, FJ Giles, AF List, T Chen, RS Allen, JA Fox, GC Michelson and JE Karp  A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia. Leukemia advance online publication 15 July 2011; doi: 10.1038/leu.2011.157

Walsby EJ, Coles SJ, Knapper S, and Burnett AK. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine. Haematologica 2011;96(3):393-399. doi:10.3324/haematol.2010.032680

Krug, Lee M. MD; Crawford, Jeffrey MD; Ettinger, David S. MD; Shapiro, Geoffrey I. MD; Spigel, David MD; Reiman, Tony MD; Temel, Jennifer S. MD; Michelson, Glenn C. MD; Young, Donald Y. MS; Hoch, Ute PhD; Adelman, Daniel C. MD Phase II Multicenter Trial of Voreloxin as Second-Line Therapy in Chemotherapy-Sensitive or Refractory Small Cell Lung Cancer. Journal of Thoracic Oncology:February 2011 - Volume 6 - Issue 2 - pp 384-386

Rachael Elizabeth Hawtin, David Elliot Stockett, Oi Kwan Wong, Cecilia Lundin, Thomas Helleday, Judith Ann Fox Homologous recombination repair is essential for repair of vosaroxin-induced DNA double-strand breaks. Oncotarget 2010; 1: 606 - 619

Ranjana H. Advani, Herbert I. Hurwitz, Michael S. Gordon, Scot W. Ebbinghaus, David S. Mendelson, Heather A. Wakelee, Ute Hoch, Jeffrey A. Silverman, Nancy A. Havrilla, Craig J. Berman, Judith A. Fox, Roberta S. Allen, Daniel C. Adelman.(2010) Voreloxin, a First-in-Class Anticancer Quinolone Derivative, in Relapsed/Refractory Solid Tumors: A Report on Two Dosing Schedules. Clin Cancer Res April 1, 2010 16:2167-2175

Hawtin RE, Stockett DE, Byl JAW, McDowell RS, Tan N, et al.(2010) Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase II. PLoS ONE 5(4): e10186. doi:10.1371/journal.pone.0010186

Scatena CD, Kumer JL, Arbitrario JP, Howlett AR, Hawtin RE, Fox JA, Silverman JA. Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically with cytarabine in vitro and induces bone marrow aplasia in vivo. Cancer Chemotherapy and Pharmacology, Volume 66, Number 5, 881-888

Fathi AT, Karp JE. New agents in acute myeloid leukemia: beyond cytarabine and anthracyclines. Curr Oncol Rep. 2009 Sep;11(5):346-52.

Hoch U, Lynch J, Sato Y, Kashimoto S, Kajikawa F, Furutani Y, Silverman JA. Voreloxin, formerly SNS-595, has potent activity against a broad panel of cancer cell lines and in vivo tumor models. Cancer Chemother Pharmacol. 2009 Jun;64(1):53-65. Epub 2008 Oct 19.

Mills DA, Fekrazad HM, Verschraegen CF. SNS-595, a naphthyridine cell cycle inhibitor and stimulator of apoptosis for the treatment of cancers. Curr Opin Investig Drugs. 2008 Jun;9(6):647-57. Review.

Tsuzuki Y, Tomita K, Shibamori K, Sato Y, Kashimoto S, Chiba K. Synthesis and structure-activity relationships of novel 7-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids as antitumor agents. Part 2. J Med Chem. 2004 Apr 8;47(8):2097-109.

Evanchik MJ, Allen D, Yoburn JC, Silverman JA, Hoch U. Metabolism of (+)-1,4-dihydro-7-(trans-3-methoxy-4-methylamino-1-pyrrolidinyl)-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid (voreloxin; formerly SNS-595), a novel replication-dependent DNA-damaging agent.Drug Metab Dispos. 2009 Mar;37(3):594-601. Epub 2008 Dec 12.

Elling RA, Tangonan BT, Penny DM, Smith JT, Vincent DE, Hansen SK, O'Brien T, Romanowski MJ. Mouse Aurora A: expression in Escherichia coli and purification. Protein expression and purification. 2007 Jul;54(1):139-46. Epub 2007 Mar 12

Cancilla, M. T., Erlanson, D. A. Tethering: Fragment-based drug discovery by mass spectrometry, pp. 305-320 in Methods and Principles in Medicinal Chemistry Volume 36: Mass Spectrometry in Medicinal Chemistry, Wanner, K. and Höfner, G, eds. Wiley-VCH (Weinheim, Germany, 2007). Series editors Mannhold, R., Kubinyi, H., Folkers, G.

Shiau TP, Erlanson DA, Gordon EM. Selective reduction of peptide isothiazolidin-3-ones. Organic letters. 2006 Dec 7;8(25):5697-9

Erlanson DA. Fragment-based lead discovery: a chemical update. Current opinion in biotechnology. 2006 Dec;17(6):643-52. Epub 2006 Nov 3. Review

Jahnke, W. and Erlanson, D. A., eds Methods and Principles in Medicinal Chemistry Volume 34: Fragment-based Approaches in Drug Discovery. Wiley-VCH (Weinheim, Germany, 2006). Series editors Mannhold, R., Kubinyi, H., Folkers, G.

Thanos CD, DeLano WL, Wells JA. Hot-spot mimicry of a cytokine receptor by a small molecule. Proceedings of the National Academy of Sciences of the United States of America. 2006 Oct 17;103(42):15422-7. Epub 2006 Oct 10

O'Brien T, Fahr BT, Sopko MM, Lam JW, Waal ND, Raimundo BC, Purkey HE, Pham P, Romanowski MJ. Structural analysis of caspase-1 inhibitors derived from Tethering. Acta crystallographica. Section F, Structural biology and crystallization communications. 2005 May 1;61(Pt 5):451-8. Epub 2005 Apr 9

Yang W, Lu W, Lu Y, Zhong M, Sun J, Thomas AE, Wilkinson JM, Fucini RV, Lam M, Randal M, Shi XP, Jacobs JW, McDowell RS, Gordon EM, Ballinger MD. Aminoethylenes: a tetrahedral intermediate isostere yielding potent inhibitors of the aspartyl protease BACE-1. Journal of medicinal chemistry. 2006 Feb 9;49(3):839-42

Fahr BT, O'Brien T, Pham P, Waal ND, Baskaran S, Raimundo BC, Lam JW, Sopko MM, Purkey HE, Romanowski MJ. Tethering identifies fragment that yields potent inhibitors of human caspase-1. Bioorganic & medicinal chemistry letters. 2006 Feb;16(3):559-62. Epub 2005 Nov 4

Yoburn JC, Baskaran S. Chemoselective arylamidine cyclizations: mild formation of 2-arylimidazole-4-carboxylic acids. Organic letters. 2005 Aug 18;7(17):3801-3

He, M. M., Smith A., Oslob J.D., Flanagan W.M., Braised, A. C., Whitty, A., Cancilla M. T., Wang, J., Lugovskoy, A.A., Yoburn, J.C., Fung, A. D., Farrington G., Eldredge, J.K., Day, E.S., Cruz, L.A., Cachero, T. G., Miller, S.K., Friedman, J.E., Choong I. C, and Cunningham, B. C. (2005) Small Molecule Inhibition of TNF-a. Science 310: 1022-1025

M.R. Arkin, "Protein-protein interactions and cancer: small molecules going in for the kill", Current Opinion in Chemical Biology, 9, 317-324 (2005).

Hansen, S., Cancilla, M., Shiau, T., Kung, J., Chen, T. and Erlanson, D. "Allosteric inhibition of PTP1B activity by selective modification of a non-active site cysteine residue", Biochemistry, 44: 7704-7712 (2005).

Buck, E., Bourne, H. and Wells, J. "Site-specific disulfide capture of agonist and antagonist peptides on the C5a receptor", Journal of Biological Chemistry, 280: 4009-4012 (2005)

Buck, E. and Wells, J. "Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor", Proceedings of the National Academy of Sciences, 102: 2719-2724 (2005)

Scheer, J.M., Wells, J.A. and Romanowski, M.J. "Malonate-assisted purification of human caspases", Protein Expression and Purification, 41:148-153 (2005).

O'Brien, T., Fahr, B.T., Sopko, M.M., Lam, J.W., Waal, N.D., Raimundo, B.C., Purkey, H.E., Pham, P. and Romanowski, M.J. "Structural analysis of caspase-1 inhibitors derived from Tethering", Acta Crystallographica, F61:451-458 (2005).

Waal, N., Yang, W., Oslob, J., Arkin, M., Hyde, J., Lu, W., McDowell, R., Yu, C. and Raimundo, B. "Identification of nonpeptidic small-molecule inhibitors of interleukin-2", Bioorganic and Medicinal Chemistry Letters, 15: 983-987 (2005).

M.R. Arkin, "Sedimentation for success", Modern Drug Discovery, 45-47 (November, 2004)

Hardy, J. and Wells, J. "Searching for new allosteric sites in enzymes", Current Opinion in Structural Biology, 14: 706-715 (2004).

Oslob, J. and Erlanson, D. "Tethering in early target assessment", Drug Discovery Today: Targets, 3: 143-150 (2004).

Hardy, J., Lam, J., Nguyen J., O'Brien, T. and Wells, J. "Discovery of an allosteric site in the caspases", Proceedings of the National Academy of Sciences, 101: 12461-12466 (2004).

Wiesmann, C., Barr, K., Kung, J., Zhu, J., Erlanson, D., Shen, W., Fahr, B., Zhong, M., Taylor, L., Randal, M., McDowell, R. and Hansen, S. "Allosteric inhibition of protein tyrosine phosphatase 1B", Nature Structural & Molecular Biology, 11: 730-737 (2004).

Erlanson, D. and Hansen, S. "Making drugs on proteins: site-directed ligand discovery for fragment-based lead assembly", Current Opinion in Chemical Biology, 8: 399-406 (2004).

Romanowski, M.J., Scheer, J., O'Brien, T and McDowell, R. "Crystal Structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding", Structure, 12: 1361-1371 (2004).

Raimundo, B., Oslob, J., Braisted, A., Hyde, J., McDowell, R., Randal, M., Waal, N., Wilkinson, J., Yu, C. and Arkin, M. "Integrating fragment assembly and biophysical methods in the chemical advancement of small-molecule antagonists of IL-2: an approach for inhibiting protein-protein interactions ", J. Med. Chem. 47: 3111-3130 (2004).

Erlanson, D., McDowell, R., and O'Brien, T. "Fragment-based drug discovery", J. Med. Chem. 47: 3463-3482 (2004).

Erlanson, D., Wells, J. and Braisted, A. "Tethering: Fragment-Based Drug Discovery", Annu. Rev. Biophys. Biomol. Struct., 33: 199-223 (2004).

Stroud, R. and Wells, J. "Mechanistic diversity of cytokine receptor signaling across cell membranes", Sci. STKE, re7 (2004).

Arkin, M. and Wells, J. "Small-molecule inhibitors of protein-protein interactions: progressing towards the dream", Nature Reviews Drug Discovery, 3: 301-317 (2004).

O'Brien, T. and Lee, D. "Prospects for Caspase Inhibitors", Mini-Reviews in Medicinal Chemistry, 4: 153-165 (2004).

Baskaran, S., Hanan, E. Byun, D. and Shen, W. "A facile reduction of 2-aminopyrimidines with triethylsilane and trifluoroacetic acid", Tetrahedron Letters, 45: 2107-2111 (2004).

Thanos, C., Randal, M., and Wells, J. "Potent small-molecule binding to a dynamic hot spot on IL-2", Journal of American Chemical Society, 125: 15280-15281 (2003).

Allen, D., Pham, Pl, Choong, I., Fahr, B., Burdett, M., Lew, W., DeLano, W., Gordon, E., Lam, J., O'Brien, T., and Lee, D. "Identification of potent and novel small-molecule inhibitors of caspase-3", Biorganic and Medicinal Chemistry Letters, 13: 3651-3655 (2003).

Nguyen, J. and Wells, J. "Direct activation of the apoptosis machinery as a mechanism to target cancer cells", Proceedings of the National Academy of Sciences, USA 100 (13): 7533-7538 (2003).

Hyde, J., Braisted, A., Randal, M., and Arkin, M. "Discovery and characterization of cooperative ligand binding in the adaptive region of interleukin-2", Biochemistry, 42 (21): 6475-6483 (2003).

Erlanson, D. A., McDowell, R. S., He, M. H., Randal, M., Simmons, R. L., Kung, J., Waight, A., Hansen, S. "Discovery of a new phosphotyrosine mimetic for PTP1B using breakaway Tethering(SM)" J. Am. Chem. Soc. 125(19) 5602-5603 (2003)

Braisted, A., Oslob, J., Delano, W., Hyde, J., McDowell, R., Waal, N., Yu, C., Arkin, M., and Raimundo, B. "Discovery of a Potent Small Molecule IL-2 Inhibitor through Fragment Assembly" J. Am. Chem. Soc. 125: 3714 - 3715 (2003)

Erlanson, D., Lam, J., Wiesmann, C., Luong, T., Simmons, R., DeLano, W., Choong, I., Burdett, M., Flanagan, M., Lee, D., Gordon, E., and O'Brien, T. "In situ assembly of enzyme inhibitors using extended tethering" Nature Biotechnology21: 308-314 (2003)

Arkin, M., Randal, M., DeLano, W., Hyde, J., Luong, T., Oslob, J., Raphael, D., Taylor, L., Wang, J., McDowell, R., Wells, J. and Braisted, A. "Binding of small molecules to an adaptive protein-protein interface" Proceedings of the National Academy of Sciences, USA 100: 1603-1608 (2003)

Choong, I.C., Lew, W., Lee, D., Pham, P., Burdett, M.T., Lam, J.W., Wiesmann, C., Luong, T.N., Fahr, B., DeLano, W.L., McDowell, R.S., Allen, D.A., Erlanson, D.A., Gordon, E.M. and O'Brien, T. "Identification of Potent and Selective Small-Molecule Inhibitors of Caspase-3 through the Use of Extended Tethering® and Structure-Based Drug Design" J. Med. Chem. 45: 5005-5022 (2002)

DeLano W.L. "Unraveling hot spots in binding interfaces: progress and challenges" Curr. Opin. Stru. Biol. 12:14-20 (2002)

Arkin, M. and Lear, J.D. "A New Data Analysis Method to Determine Binding Constants of Small Molecules to Proteins Using Equilibrium Analytical Ultracentrifugation with Absorption Optics" Analytical Biochemistry 299, 98-107 (2001)

Delano, W.L, Ultsch, M.H., De Vos, A.A., Wells, J.A "Convergent Solutions to Binding at a Protein-Protein Interface" Science 287: 1279-1283 (2000)

Erlanson, D.A., Braisted, A.C., Raphael, D.R., Randal, M., Stroud, R.M., Gordon, E.M., Wells, J.A. "Site-Directed Ligand Discovery" PNAS 19: 9367-9372. (2000)

Clackson, T., Ultsch, M., Wells, J.A. and De Vos, A.A. "Structural and Functional Analysis of the 1:1 Growth Hormone:Receptor Complex Reveals the Molecular Basis for Receptor Affinity" J. Mol. Biol. 277: 1111-1128. (1998)

Atwell, S., Ultsch, M., De Vos, A.M. and Wells, J.A. "Structural Plasticity in a Remodeled Protein-Protein Interface" Science 278: 1124-1127 (1997)

Clackson, T. and Wells, J.A. "A Hot Spot of Binding Energy in a Hormone-Receptor Interface" Science 267, 383-386 (1995)

Cunningham, B.C. and Wells, J.A. "Comparison of a Structural and Functional Epitope" J. Mol. Biol. 234: 554-563 (1993)