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

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
   PubMedGoogle Scholar
• Rowinsky EK, Chaudhry V, Cornblath DR, Donehower RC. Neurotoxicity of Taxol. J Natl Cancer Inst Monogr 1993;15:107-15
   PubMedGoogle Scholar
• Cole SP, Spars KE, Fraser K, et al. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 1994;54:5902-10
   PubMed Web of Science ®Google Scholar
• Heald R. Motor function in the mitotic spindle. Cell 2000;102:399-402
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Sarli V, Giannis A. Inhibitors of mitotic kinesins: next-generation antimitotics. ChemMedChem 2006;1:293-8
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Jiang C, You Q, Li Z, Guo Q. Kinesin spindle protein inhibitors as anticancer agents. Expert Opin Ther Patents 2006;16:1517-32
   Web of Science ®Google Scholar
• Matsuno K, Sawada J, Asai A. Therapeutic potential of mitotic kinesin inhibitors in cancer. Expert Opin Ther Patents 2008;18:253-74
   Web of Science ®Google Scholar
• Zhang Y, Xu W. Progress on kinesin spindle protein inhibitors as anti-cancer agents. Anticancer Agents Med Chem 2008;8:698-704
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• Jiang C, Zhang XJ, Shen Z, You QD. Kinesin spindle protein Inhibitors. Prog Chem 2010;22:153-62
   Web of Science ®Google Scholar
• El-Nassan HB. Advances in the discovery of kinesin spindle protein (Eg5) inhibitors as antitumor agents. Eur J Med Chem 2013;62:614-31
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Klein E, DeBonis S, Thiede B, et al. New chemical tools for investigating human mitotic kinesin Eg5. Bioorg Med Chem 2007;15:6474-88
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Cytokinetics, Inc. Methods and compositions utilizing quinazolinones as KSP kinesin inhibitors and their preparation. US20080182864; 2008
   Google Scholar
• Cytokinetics, Inc. Methods of treating lung disease using mitotic kinesin inhibitors in combination with another therapy. WO2012009097; 2012
   Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 4SC AG. Preparation of pyrazolotriazines as kinesin Eg5 inhibitors having antiproliferative and/or apoptosis inducing activity. WO2009074677; 2009
   Google Scholar
• Taigen Biotechnology Co., Ltd. Preparation of 4-oxoquinazoline derivatives as kinesin inhibitors. WO2008147852; 2008
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   PubMedGoogle Scholar
• 4SC AG. Preparation of enantiomerically pure indolopyridines containing tetrahydro-β-carboline-hydantoins. WO2009109620; 2009
   Google Scholar
• 4SC AG. Indolopyridines as inhibitors of the kinesin spindle protein (Eg5). WO2009024190; 2009
   Google Scholar
• 4SC AG. Tetracyclic indolopyridines as Eg5 inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2009024613; 2009
   Google Scholar
• 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
   Google Scholar
• 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
   Google Scholar
• 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
   Google Scholar
• 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
   PubMedGoogle Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Pharma Ip Ltd Liability Intermediary Corp. Eg5 inhibitor and agent for treatment of cell proliferative disease containing the same. WO2008114505; 2008
   Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• Arrowhead Center, Inc. Preparation of tritylcysteinols and tritylcysteines as selective inhibitors of Eg5 motors. US8349899; 2013
   Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Schering Corp. Preparation of pyrrolidine derivatives for inhibition of KSP activity. WO2009061597; 2009
   Google Scholar
• Nycomed GmbH. Benzopyranopyrazoles as Eg5 inhibitory activity and their preparation, pharmaceutical compositions and use in the treatment of proliferative diseases. WO2008006883; 2008
   Google Scholar
• Schering Corp. Preparation of spiro-fused pyrazoles as inhibititors of kinesin spindle protein (KSP) kinesin activity. WO2009061596; 2009
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Array BioPharma Inc. Oxadiazole and thiadiazole derivatives as mitotic kinesin inhibitors and their preparation and use in the treatment of diseases. US20080182992; 2008
   Google Scholar
• Schering Corp. Preparation of spiro 1,3,4-thiadiazoline derivatives as KSP inhibitors. WO2010132520; 2010
   Google Scholar
• Schering Corp. Preparation of spiro-condensed 1,3,4-thiadiazole derivatives for inhibiting KSP kinesin activity. WO2009052288; 2009
   Google Scholar
• Schering Corp. Preparation of oxadiazole derivatives for inhibition of KSP activity. WO2009061595; 2009
   Google Scholar
• 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
   Google Scholar
• Liu F, You Q, Chen Y. Pharmacophore identification of KSP inhibitors. Bioorg Med Chem Lett 2007;17:722-6
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Novartis AG. Kinesin inhibitors as cancer therapeutics. WO2009077448; 2009
   Google Scholar
• Novartis AG. Preparation of phenylthiazole derivatives and analogs for use as KSP inhibitors. WO2011128388; 2011
   Google Scholar
• Novartis A.-G. Preparation of substituted triazole derivatives for use as KSP inhibitors. WO2008063912; 2008
   Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   Google Scholar
• Parrish CA, Adams ND, Auge KR, et al. Novel ATP-competitive kinesin spindle protein inhibitors. J Med Chem 2007;50:4939-52
   PubMed Web of Science ®Google Scholar
• 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
   Google Scholar
• 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
   PubMedGoogle Scholar
• 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
   Google Scholar
• Sanofi. Preparation of tetrahydrocarboline derivatives as Eg5 inhibitors for treating cell proliferation disorders. WO2011084439; 2011
   Google Scholar
• Kyoto University and Pharma IP Y. K. Preparation of 9H-carbazole and 9H-pyrido[3,4-b]indole derivatives as Eg5 inhibitors. WO2010073719; 2010
   Google Scholar
• 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
   Google Scholar
• Louisiana State University and Agricultural and Mechanical College. Protein structural biomarkers to guide targeted chemotherapies. WO2010096680; 2010
   Google Scholar