Small Molecule R1498 as a Well-Tolerated and Orally Active Kinase Inhibitor for Hepatocellular Carcinoma and Gastric Cancer Treatment via Targeting Angiogenesis and Mitosis Pathways

PLoS ONE

Volumn 8, Issue 6, 2013, Pages

  Zhang, Chao ^a   Wu, Xihan ^a   Zhang, Meifang ^a   Zhu, Liangcheng ^a   Zhao, Rong ^a   Xu, Danqing ^a   Lin, Zhaohu ^a   Liang, Chungen ^a   Chen, Taiping ^b   Chen, Li ^a   Ren, Yi ^a   Zhang, Joe ^a   Qin, Ning ^a   Zhang, Xiongwen ^a  

^a Roche Pharma Research and Early Development China   (China)

^b Crown Bioscience Inc   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; AURORA A KINASE; AURORA B KINASE; R 1498; SORAFENIB; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2; AURKA PROTEIN, HUMAN; BENZODIAZEPINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE; R1498 COMPOUND; VASCULOTROPIN A;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER INHIBITION; CANCER REGRESSION; CELL ASSAY; CELL CYCLE ARREST; CONTROLLED STUDY; DOWN REGULATION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL CARCINOMA; MALE; MOUSE; NONHUMAN; RAT; STOMACH CANCER; TUMOR VASCULARIZATION; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; CARCINOMA, HEPATOCELLULAR; CELL CYCLE CHECKPOINT; CELL PROLIFERATION; DOG; DRUG EFFECTS; DRUG SCREENING; LIVER NEOPLASMS; METABOLISM; MITOSIS; NEOVASCULARIZATION, PATHOLOGIC; NUDE MOUSE; ORAL DRUG ADMINISTRATION; PATHOLOGY; PHYSIOLOGY; PROTEIN PROCESSING; SIGNAL TRANSDUCTION; STOMACH NEOPLASMS; TUMOR CELL LINE; TUMOR VOLUME; UMBILICAL VEIN ENDOTHELIAL CELL; VASCULARIZATION; WISTAR RAT;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; AURORA KINASE A; BENZODIAZEPINES; CARCINOMA, HEPATOCELLULAR; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL PROLIFERATION; DOGS; FEMALE; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; LIVER NEOPLASMS; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; MITOSIS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN KINASE INHIBITORS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PYRAZOLES; RATS; RATS, WISTAR; SIGNAL TRANSDUCTION; STOMACH NEOPLASMS; TUMOR BURDEN; VASCULAR ENDOTHELIAL GROWTH FACTOR A; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84878746621     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0065264     Document Type: Article

References (31)

1. Dancey JE, Chen HX, (2006) Strategies for optimizing combinations of molecularly targeted anticancer agents. Nat Rev Drug Discov 5: 649-659.
2. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, et al. (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390.
3. Xie B, Wang DH, Spechler SJ, (2012) Sorafenib for treatment of hepatocellular carcinoma: a systematic review. Dig Dis Sci 57: 1122-1129.
4. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, et al. (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376: 687-697.
5. Nahta R, Esteva FJ, (2007) Trastuzumab: triumphs and tribulations. Oncogene 26: 3637-3643.
6. Ferrara N, Hillan KJ, Gerber HP, Novotny W, (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3: 391-400.
7. Ferrara N, (2011) From the discovery of vascular endothelial growth factor to the introduction of avastin in clinical trials- an interview with Napoleone Ferrara by Domenico Ribatti. Int J Dev Biol 55: 383-388.
8. Donate F, Parry GC, Shaked Y, Hensley H, Guan X, et al. (2008) Pharmacology of the novel antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2): observation of a U-shaped dose-response curve in several preclinical models of angiogenesis and tumor growth. Clin Cancer Res 14: 2137-2144.
9. Jain RK, Duda DG, Clark JW, Loeffler JS, (2006) Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 3: 24-40.
10. Shojaei F, (2012) Anti-angiogenesis therapy in cancer: Current challenges and future perspectives. Cancer Lett 320: 130-137.
11. Arbab AS, (2012) Activation of alternative pathways of angiogenesis and involvement of stem cells following anti-angiogenesis treatment in glioma. Histol Histopathol 27: 549-557.
12. Ferrara N, Mass RD, Campa C, Kim R, (2007) Targeting VEGF-A to treat cancer and age-related macular degeneration. Annu Rev Med 58: 491-504.
13. Vischioni B, Oudejans JJ, Vos W, Rodriguez JA, Giaccone G, (2006) Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients. Mol Cancer Ther 5: 2905-2913.
14. Dar AA, Zaika A, Piazuelo MB, Correa P, Koyama T, et al. (2008) Frequent overexpression of Aurora Kinase A in upper gastrointestinal adenocarcinomas correlates with potent antiapoptotic functions. Cancer 112: 1688-1698.
15. Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, et al. (2004) VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 10: 262-267.
16. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, et al. (2008) A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 26: 127-132.
17. Zhang C, Yang F, Zhang XW, Wang SC, Li MH, et al. (2006) Grateloupia longifolia polysaccharide inhibits angiogenesis by downregulating tissue factor expression in HMEC-1 endothelial cells. Br J Pharmacol 148: 741-751.
18. Zhang C, Yang N, Yang CH, Ding HS, Luo C, et al. (2009) S9, a novel anticancer agent, exerts its anti-proliferative activity by interfering with both PI3K-Akt-mTOR signaling and microtubule cytoskeleton. PLoS One 4: e4881.
19. Liu JJ, Daniewski I, Ding Q, Higgins B, Ju G, et al. (2010) Pyrazolobenzodiazepines: part I. Synthesis and SAR of a potent class of kinase inhibitors. Bioorg Med Chem Lett 20: 5984-5987.
20. Bayliss R, Sardon T, Vernos I, Conti E, (2003) Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell 12: 851-862.
21. Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, et al. (2002) Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol 22: 874-885.
22. Hata T, Furukawa T, Sunamura M, Egawa S, Motoi F, et al. (2005) RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res 65: 2899-2905.
23. Sun W, Powell M, O'Dwyer PJ, Catalano P, Ansari RH, et al. (2010) Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203. J Clin Oncol 28: 2947-2951.
24. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, et al. (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64: 7099-7109.
25. Fletcher GC, Brokx RD, Denny TA, Hembrough TA, Plum SM, et al. (2011) ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther 10: 126-137.
26. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, et al. (2011) Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 129: 245-255.
27. Minor DR, Kashani-Sabet M, Garrido M, O'Day SJ, Hamid O, et al. (2012) Sunitinib Therapy for Melanoma Patients with KIT Mutations. Clin Cancer Res.
28. Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, et al. (2006) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24: 16-24.
29. Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N, et al. (2011) Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol 29: 3960-3967.
30. Herbst RS, (2005) Role of novel targeted therapies in the clinic. Br J Cancer 92Suppl 1: S21-27.
31. Hanahan D, Weinberg RA, (2011) Hallmarks of cancer: the next generation. Cell 144: 646-674.