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Kinesin spindle protein inhibitors in cancer: a patent review (2008 – present)

, PhD & , PhD
Pages 1547-1560 | Published online: 26 Aug 2013

Bibliography

  • Wood KW, Cornwell WD, Jackson JR. Past and future of the mitotic spindle as an oncology target. Curr Opin Pharmacol 2001;1:370-7
  • Rowinsky EK, Chaudhry V, Cornblath DR, Donehower RC. Neurotoxicity of Taxol. J Natl Cancer Inst Monogr 1993;15:107-15
  • Cole SP, Spars KE, Fraser K, et al. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 1994;54:5902-10
  • Heald R. Motor function in the mitotic spindle. Cell 2000;102:399-402
  • Masuda A, Maeno K, Nakagawa T, et al. Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by anti-microtubule agents in human lung cancers. Am J Pathol 2003;163:1109-16
  • Sarli V, Giannis A. Inhibitors of mitotic kinesins: next-generation antimitotics. ChemMedChem 2006;1:293-8
  • Hayashi N, Koller E, Fazli L, Gleave ME. Effects of Eg5 knockdown on human prostate cancer xenograft growth and chemosensitivity. Prostate 2008;68:1283-95
  • Liu M, Yu H, Huo L, et al. Validating the mitotic kinesin Eg5 as a therapeutic target in pancreatic cancer cells and tumor xenografts using a specific inhibitor. Biochem Pharmacol 2008;76:169-78
  • Nakai R, Iida S, Takahashi T, et al. K858, a novel inhibitor of mitotic kinesin Eg5 and antitumor agent, induces cell death in cancer cells. Cancer Res 2009;69:3901-9
  • Jiang C, You Q, Li Z, Guo Q. Kinesin spindle protein inhibitors as anticancer agents. Expert Opin Ther Patents 2006;16:1517-32
  • Matsuno K, Sawada J, Asai A. Therapeutic potential of mitotic kinesin inhibitors in cancer. Expert Opin Ther Patents 2008;18:253-74
  • Zhang Y, Xu W. Progress on kinesin spindle protein inhibitors as anti-cancer agents. Anticancer Agents Med Chem 2008;8:698-704
  • Knigh SD, Parrish CA. Recent progress in the identification and clinical evaluation of inhibitors of the mitotic kinesin KSP. Curr Top Med Chem 2008;8:888-904
  • Jiang C, Zhang XJ, Shen Z, You QD. Kinesin spindle protein Inhibitors. Prog Chem 2010;22:153-62
  • El-Nassan HB. Advances in the discovery of kinesin spindle protein (Eg5) inhibitors as antitumor agents. Eur J Med Chem 2013;62:614-31
  • Mayer TU, Kapoor TM, Haggarty SJ, et al. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999;286:971-4
  • Gartner M, Sunder-Plassmann N, Seiler J, et al. Development and biological evaluation of potent and specific inhibitors of mitotic kinesin Eg5. ChemBioChem 2005;6:1173-7
  • Liu M, Yu H, Huo L, et al. Validating the mitotic kinesin Eg5 as a therapeutic target in pancreatic cancer cells and tumor xenografts using a specific inhibitor. Biochem Pharmacol 2008;76:169-78
  • Prokopcov H, Dallinger D, Uray G, et al. Structure-activity relationships and molecular docking of novel dihydropyrimidine-based mitotic Eg5 inhibitors. ChemMedChem 2010;5:1760-9
  • Kaan HYK, Ulaganathan V, Rath O, et al. Structural basis for inhibition of Eg5 by dihydropyrimidines: stereoselectivity of antimitotic inhibitors enastron, imethylenastron and fluorastrol. J Med Chem 2010;53:5676-83
  • Yang L, Jiang C, Liu F, et al. Cloning, enzyme characterization of recombinant human Eg5 and the development of a new Inhibitor. Biol Pharm Bull 2008;31:1397-402
  • Fu RG, You QD, Yang L, et al. Design, synthesis and bioevaluation of dihydropyrazolo[3,4-b]pyridine and benzo[4,5]imidazo[1,2-a]pyrimidine compounds as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents. Bioorg Med Chem 2010;18:8035-43
  • Klein E, DeBonis S, Thiede B, et al. New chemical tools for investigating human mitotic kinesin Eg5. Bioorg Med Chem 2007;15:6474-88
  • Svetlik J, Veizerov L, Mayer TU, Catarinella M. Monastrol analogs: a synthesis of pyrazolopyridine, benzopyranopyrazolopyridine, and oxygenbridged azolopyrimidine derivatives and their biological screening. Bioorg Med Chem Lett 2010;20:4073-6
  • Johnson RK, McCabe FL, Cauder E, et al. SB-715992, a potent and selective inhibitor of KSP mitotic kinesin, demonstrates broad-spectrum activity in advanced murine tumors and human tumor xenografts. Proc Annu Meet Am Assoc Cancer Res 2002;43:269
  • Zhang B, Liu J, Xu Y, Ng S. Crystal structure of HsEg5 in complex with clinical candidate CK0238273 provides insight into inhibitory mechanism, potency, and specificity. Biochem Biophys Res Commun 2008;372:565-70
  • Tang PA, Siu LL, Chen EX, et al. Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck. Invest New Drugs 2008;26:257-64
  • Beer TM, Goldman B, Synold TW, et al. Southwest oncology group phase II study of ispinesib in androgenindependent prostate cancer previously treated with taxanes. Clin Genitourin Cancer 2008;6:103-9
  • Purcell JW, Davis J, Reddy M, et al. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast Cancer. Clin Cancer Res 2010;16:566-76
  • Carol H, Lock R, Houghton PJ, et al. Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. Pediatr Blood Cancer 2009;53:1255-63
  • Souid A, Dubowy RL, Ingle AM, et al. A pediatric phase 1 trial and pharmacokinetic study of ispinesib: a children's oncology group phase I consortium study. Pediatr Blood Cancer 2010;55:1323-8
  • Cytokinetics, Inc. Methods and compositions utilizing quinazolinones as KSP kinesin inhibitors and their preparation. US20080182864; 2008
  • Cytokinetics, Inc. Methods of treating lung disease using mitotic kinesin inhibitors in combination with another therapy. WO2012009097; 2012
  • Jackson JR, Gilmartin A, Dhanak D, et al. A second generation KSP inhibitor, SB-743921, is a highly potent and active therapeutic in preclinical models of cancer. Proc Am Assoc Cancer Res 2006; B1
  • Holen KD, Belani CP, Wilding G, et al. A first in human study of SB-743921, a kinesin spindle protein inhibitor, to determine pharmacokinetics, biologic effects and establish a recommended phase II dose. Cancer Chemother Pharmacol 2011;67:447-54
  • 4SC AG. Preparation of pyrazolotriazines as kinesin Eg5 inhibitors having antiproliferative and/or apoptosis inducing activity. WO2009074677; 2009
  • Taigen Biotechnology Co., Ltd. Preparation of 4-oxoquinazoline derivatives as kinesin inhibitors. WO2008147852; 2008
  • Jiang C, Yang L, Wu WT, et al. De novo design, synthesis and biological evaluation of 1,4-dihydroquinolin-4-ones and 1,2,3,4-tetrahydroquinazolin-4-ones as potent kinesin spindle protein (KSP) inhibitors. Bioorg Med Chem 2011;19:5612-27
  • Hotha S, Yarrow JC, Yang JG, et al. HR22C16: a potent small-molecule probe for the dynamics of cell division. Angew Chem Int Ed 2003;42:2379-82
  • Xiao S, Shi X. The first highly stereoselective approach to the mitotic kinesin Eg5 inhibitor HR22C16 and its analogues. Tetrahedron Asymmetry 2010;21:226-31
  • Sunder-Plassmann S, Sarli V, Gartner M, et al. Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5. Bioorg Med Chem 2005;13:6094-111
  • 4SC AG. Preparation of enantiomerically pure indolopyridines containing tetrahydro-β-carboline-hydantoins. WO2009109620; 2009
  • 4SC AG. Indolopyridines as inhibitors of the kinesin spindle protein (Eg5). WO2009024190; 2009
  • 4SC AG. Tetracyclic indolopyridines as Eg5 inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2009024613; 2009
  • Barsanti PA, Wang W, Ni Z, et al. The discovery of tetrahydro-b-carbolines as inhibitors of the kinesin Eg5. Bioorg Med Chem Lett 2010;20:157-60
  • Liu F, Yu L, Jiang C, et al. Discovery of tetrahydro-α-carbolines as inhibitors of the mitotic kinesin KSP. Bioorg Med Chem 2010;18:4167-77
  • Zee-Cheng KY, Cheng CC. Experimental antileukemic agents. Preparation and structure-activity study of S-tritylcysteine and related compounds. J Med Chem 1970;13:414-18
  • Paull KD, Lin CM, Malspeis L, Hamel E. Identification of novel antimitotic agents acting at the tubulin level by computer-assisted evaluation of differential cytotoxicity data. Cancer Res 1992;52:3892-900
  • Brier S, Lemaire D, Debonis S, et al. Identification of the protein binding region of S-trityl-L-cysteine, a new potent inhibitor of the mitotic kinesin Eg5. Biochemistry 2004;43:13072-82
  • Skoufias DA, DeBonisv S, Saoudi Y, et al. S-Trityl-L-cysteine is a reversible, tight binding inhibitor of the human kinesin Eg5 that specifically blocks mitotic progression. J Biol Chem 2006;281:17559-69
  • Kaan HYK, Ulaganathan V, Hackney DD, Kozielski F. An allosteric transition trapped in an intermediate state of a new kinesin inhibitor complex. Biochem J 2009;425:55-60
  • Ogo N, Oishi S, Matsuno K, et al. Synthesis and biological evaluation of L-cysteine derivatives as mitotic kinesin Eg5 inhibitors. Bioorg Med Chem Lett 2007;17:3921-4
  • Pharma Ip Ltd Liability Intermediary Corp. Eg5 inhibitor and agent for treatment of cell proliferative disease containing the same. WO2008114505; 2008
  • DeBonis S, Skoufias DA, Indorato R, et al. Structure-activity relationship of S-trityl-L-cysteine analogues as inhibitors of the human mitotic kinesin Eg5. J Med Chem 2008;51:1115-25
  • Shimizu M, Ishii H, Ogo N, et al. S-Trityl-L-cysteine derivative induces caspase-independent cell death in K562 human chronic myeloid leukemia cell line. Cancer Lett 2010;298:99-106
  • Kaan HYK, Weiss J, Menger D, et al. Structure-activity relationship and multidrug resistance study of new S-trityl-L-cysteine derivatives as inhibitors of Eg5. J Med Chem 2011;54:1576-86
  • Ding S, Nishizawa K, Kobayashi T, et al. A potent chemotherapeutic strategy for bladder cancer: (S)-methoxy-trityl-L-cysteine, a novel Eg5 inhibitor. J Urol 2010;184:1175-81
  • Xing ND, Ding ST, Saito R, et al. A potent chemotherapeutic strategy in prostate cancer: S-(methoxytrityl)-L-cysteine, a novel Eg5 inhibitor. Asian J Androl 2011;13:236-41
  • Shimizu M, Ishii H, Ogo N, et al. Biochemical analysis of cellular target of S-trityl-L-cysteine derivatives using affinity matrix. Bioorg Med Chem Lett 2010;20:1578-80
  • Arrowhead Center, Inc. Preparation of tritylcysteinols and tritylcysteines as selective inhibitors of Eg5 motors. US8349899; 2013
  • Rodriguez D, Ramesh C, Henson LH, et al. Synthesis and characterization of tritylthioethanamine derivatives with potent KSP inhibitory activity. Bioorg Med Chem 2011;19:5446-53
  • Wang F, Good JAD, Rath O, et al. Triphenylbutanamines: kinesin spindle protein inhibitors with in vivo antitumor activity. J Med Chem 2012;55:1511-25
  • Abualhasan MN, Good JAD, Wittayanarakul K, et al. Doing the methylene shuffle further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine. Eur J Med Chem 2012;54:483-98
  • Cox CD, Coleman PJ, Breslin MJ, et al. Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane refractory cancer. J Med Chem 2008;51:4239-52
  • Holen K, DiPaola R, Liu G, et al. A phase I trial of MK-0731, a kinesin spindle protein (KSP) inhibitor, in patients with solid tumors. Invest New Drugs 2012;30:1088-95
  • Schering Corp. Preparation of pyrrolidine derivatives for inhibition of KSP activity. WO2009061597; 2009
  • Nycomed GmbH. Benzopyranopyrazoles as Eg5 inhibitory activity and their preparation, pharmaceutical compositions and use in the treatment of proliferative diseases. WO2008006883; 2008
  • Schering Corp. Preparation of spiro-fused pyrazoles as inhibititors of kinesin spindle protein (KSP) kinesin activity. WO2009061596; 2009
  • Nakai R, Iida S, Takahashi T, et al. K858, a novel inhibitor of mitotic kinesin Eg5 and antitumor agent, induces cell death in cancer cells. Cancer Res 2009;69:3901-9
  • Woessner R, Tunquist B, Lemieux C, et al. ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models. Anticancer Res 2009;29:4373-80
  • Kim KH, Xie Y, Tytler EM, et al. KSP inhibitor ARRY-520 as a substitute for paclitaxel in type I ovarian cancer cells. J Trans Med 2009;7:63-71
  • Carter BZ, Mak DH, Woessner R, et al. Inhibition of KSP by ARRY-520 induces cell cycle block and cell death via the mitochondrial pathway in AML cells. Leukemia 2009;23:1755-62
  • Khoury HJ, Garcia-Manero G, Borthakur G, et al. A phase 1 doseescalation study of ARRY-520, a kinesin spindle protein inhibitor, in patients with advanced myeloid leukemias. Cancer 2012;118:3556-64
  • Array BioPharma Inc. Oxadiazole and thiadiazole derivatives as mitotic kinesin inhibitors and their preparation and use in the treatment of diseases. US20080182992; 2008
  • Schering Corp. Preparation of spiro 1,3,4-thiadiazoline derivatives as KSP inhibitors. WO2010132520; 2010
  • Schering Corp. Preparation of spiro-condensed 1,3,4-thiadiazole derivatives for inhibiting KSP kinesin activity. WO2009052288; 2009
  • Schering Corp. Preparation of oxadiazole derivatives for inhibition of KSP activity. WO2009061595; 2009
  • Basso AD, Liu M, Dai C, et al. SCH 2047069, a novel oral kinesin spindle protein inhibitor, shows single-agent antitumor activity and enhances the efficacy of chemotherapeutics. Mol Cancer Ther 2010;9:2993-3002
  • Liu F, You Q, Chen Y. Pharmacophore identification of KSP inhibitors. Bioorg Med Chem Lett 2007;17:722-6
  • Jiang C, You Q, Liu F, et al. Design, synthesis and evaluation of tetrahydroisoquinolines as new kinesin spindle protein inhibitors. Chem Pharm Bull 2009;57:567-71
  • Schering Corp. Benzimidazole derivatives and related compounds for inhibiting KSP kinesin activity and their preparation and use in the treatment of KSP-associated diseases. WO2008153701; 2008
  • Lahue BR, Ma Y, Shipps GW, et al. Substituted benzimidazoles: a novel chemotype for small molecule hKSP inhibitors. Bioorg Med Chem Lett 2009;19:3405-9
  • Jiang C, Yang L, Wu W, et al. CPUYJ039, a newly synthesized benzimidazole-based compound, is proved to be a novel inducer of apoptosis in HCT116 cells with potent KSP inhibitory activity. J Pharm Pharmacol 2011;63:1462-9
  • Novartis AG. Kinesin inhibitors as cancer therapeutics. WO2009077448; 2009
  • Novartis AG. Preparation of phenylthiazole derivatives and analogs for use as KSP inhibitors. WO2011128388; 2011
  • Novartis A.-G. Preparation of substituted triazole derivatives for use as KSP inhibitors. WO2008063912; 2008
  • Nagarajan S, Skoufias DA, Kozielski F, Pae AN. Receptor-ligand interaction-based virtual screening for novel Eg5/kinesin spindle protein inhibitors. J Med Chem 2012;55:2561-73
  • Fujitsu Ltd. Preparation of N-benzyl-N-(indenyl or indanyl)acetamide derivatives as novel inhibitors of kinesin spindle protein (KSP) for treatment of cancer. WO2012073375; 2012
  • Schering Corp. Pyrrolo[3,2-a]pyridine derivatives for inhibiting KSP kinesin activity and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2008079293; 2008
  • Parrish CA, Adams ND, Auge KR, et al. Novel ATP-competitive kinesin spindle protein inhibitors. J Med Chem 2007;50:4939-52
  • Luo L, Parrish CA, Nevins N, et al. ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism. Nat Chem Biol 2007;33:722-6
  • Matsuno K, Sawada J, Sugimoto M, et al. Bis(hetero)aryl derivatives as unique kinesin spindle protein inhibitors. Bioorg Med Chem Lett 2009;19:1058-61
  • Oishi S, Watanabe T, Sawada J, et al. Kinesin spindle protein (KSP) inhibitors with 2,3-fused indole scaffolds. J Med Chem 2010;53:5054-8
  • Sanofi. Preparation of tetrahydrocarboline derivatives as Eg5 inhibitors for treating cell proliferation disorders. WO2011084439; 2011
  • Kyoto University and Pharma IP Y. K. Preparation of 9H-carbazole and 9H-pyrido[3,4-b]indole derivatives as Eg5 inhibitors. WO2010073719; 2010
  • Takeuchi T, Oishi S, Watanabe T, et al. Structure activity relationships of carboline and carbazole derivatives as a novel class of ATP-competitive kinesin spindle protein inhibitors. J Med Chem 2011;54:4839-46
  • Louisiana State University and Agricultural and Mechanical College. Protein structural biomarkers to guide targeted chemotherapies. WO2010096680; 2010

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