EMD 1214063 and EMD 1204831 constitute a new class of potent and highly selective c-Met inhibitors

Clinical Cancer Research

Volumn 19, Issue 11, 2013, Pages 2941-2951

  Bladt, Friedhelm ^a   Faden, Bettina ^a   Friese Hamim, Manja ^a   Knuehl, Christine ^a   Wilm, Claudia ^a   Fittschen, Claus ^a   Grädler, Ulrich ^a   Meyring, Michael ^a   Dorsch, Dieter ^a   Jaehrling, Frank ^a   Pehl, Ulrich ^a   Stieber, Frank ^a   Schadt, Oliver ^a   Blaukat, Andree ^a  

^a Merck Serono GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

[3 [1 [3 [5 (1 METHYLPIPERIDIN 4 YLMETHOXY)PYRIMIDIN 2 YL]BENZYL] 1,6 DIHYDRO 6 OXO PYRIDAZIN 3 YL]BENZONITRILE]; [4 [2 [2 [3 [3 (1 METHYL 1H PYRAZOL 4 YL) 6 OXO 1,6 DIHYDRO PYRIDAZIN 1 YLMETHYL]PHENYL]PYRIMIDIN 5 YLOXY]ETHYL]MORPHOLINE]; ANTINEOPLASTIC AGENT; EMD 1204831; EMD 1214063; PROTEIN INHIBITOR; PROTEIN TYROSINE KINASE; SCATTER FACTOR RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CANCER REGRESSION; CELL CYCLE ARREST; CELL MIGRATION; CELL MOTILITY; CELL PROLIFERATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG DETERMINATION; DRUG DISTRIBUTION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG MEGADOSE; DRUG PROTEIN BINDING; DRUG SYNTHESIS; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MASS SPECTROMETRY; MOUSE; NEOPLASM; NONHUMAN; PANCREAS CARCINOMA; PHARMACODYNAMICS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; TANDEM MASS SPECTROMETRY; TREATMENT DURATION; TUMOR XENOGRAFT; WEIGHT REDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MICE; MORPHOLINES; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MET; PYRIDAZINES; PYRIMIDINES; SIGNAL TRANSDUCTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84879001675     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-12-3247     Document Type: Article

References (28)

1. Eder JP, Vande Woude GF, Boerner SA, LoRusso PM. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin Cancer Res 2009;15:2207-14.
2. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003;4:915-25. (Pubitemid 37493640)
3. Bladt F, Riethmacher D, Isenmann S, Aguzzi A, Birchmeier C. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 1995;376:768-71.
4. Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W, Sharpe M, et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995;373:699-702.
5. Liu Y, Tolbert EM, Lin L, Thursby MA, Sun AM, Nakamura T, et al. Up-regulation of hepatocyte growth factor receptor: an amplification and targeting mechanism for hepatocyte growth factor action in acute renal failure. Kidney Int 1999;55:442-53. (Pubitemid 29082871)
6. Xian CJ, Couper R, Howarth GS, Read LC, Kallincos NC. Increased expression ofHGFand c-met in rat small intestine during recovery from methotrexate-induced mucositis. Br J Cancer 2000;82:945-52. (Pubitemid 30085250)
7. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 2008;7:504-16. (Pubitemid 351767118)
8. Goetsch L, Caussanel V. Selection criteria for c-Met-targeted therapies: emerging evidence for biomarkers. Biomark Med 2010;4:149-70.
9. Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997;16:68-73. (Pubitemid 27198158)
10. Toschi L, Cappuzzo F. Clinical implications of MET gene copy number in lung cancer. Future Oncol 2010;6:239-47.
11. Oxnard GR, Arcila ME, Chmielecki J, Ladanyi M, Miller VA, Pao W. New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer. Clin Cancer Res 2011;17:5530-7.
12. Guessous F, Zhang Y, diPierro C, Marcinkiewicz L, Sarkaria J, Schiff D, et al. An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anticancer Agents Med Chem 2010;10:28-35.
13. Li Y, Li A, Glas M, Lal B, Ying M, Sang Y, et al. c-Met signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype. Proc Natl Acad Sci U S A 2011;108:9951-6.
14. Buchanan SG, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, et al. SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther 2009;8:3181-90.
15. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, et al. The selectivity of protein kinase inhibitors: a further update. Biochem J 2007;408:297-315.
16. Liu X, Wang Q, Yang G, Marando C, Koblish HK, Hall LM, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin Cancer Res 2011;17:7127-38.
17. Asaoka Y, Tada M, Ikenoue T, Seto M, Imai M, Miyabayashi K, et al. Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion. Biochem Biophys Res Commun 2010;394:1042-6.
18. Lutterbach B, Zeng Q, Davis LJ, Hatch H, Hang G, Kohl NE, et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res 2007;67:2081-8. (Pubitemid 46424226)
19. Jin H, Yang R, Zheng Z, Romero M, Ross J, Bou-Reslan H, et al. MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Res 2008;68:4360-8.
20. Zou HY, Li Q, Lee JH, Arango ME, Burgess K, Qiu M, et al. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther 2012;11:1036-47.
21. Wang JY, Del Valle L, Gordon J, Rubini M, Romano G, Croul S, et al. Activation of the IGF-IR system contributes to malignant growth of human and mouse medulloblastomas. Oncogene 2001;20:3857-68. (Pubitemid 32646196)
22. Patanè S, Avnet S, Coltella N, Costa B, Sponza S, Olivero M, et al. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res 2006;66:4750-7.
23. Joffre C, Barrow R, Ménard L, Calleja V, Hart IR, Kermorgant S. A direct role for Met endocytosis in tumorigenesis. Nat Cell Biol 2011;13:827-37.
24. Underiner TL, Herbertz T, Miknyoczki SJ. Discovery of small molecule c-Met inhibitors: Evolution and profi les of clinical candidates. Anticancer Agents Med Chem 2010;10:7-27.
25. Liu X, Newton RC, Scherle PA. Developing c-MET pathway inhibitors for cancer therapy: progress and challenges. Trends Mol Med 2010;16:37-45.
26. Perera T. Selective inhibition of Met kinase: JNJ38877605. Spring CTEP Early Drug Development Meeting, Rockville, MD; 2007.
27. Cepero V, Sierra JR, Corso S, Ghiso E, Casorzo L, Perera T, et al. MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors. Cancer Res 2010;70:7580-90.
28. Liu Y, Wang T, Yan J, Jiagbogu N, Heideman DA, Canfield AE, et al. HGF/c-Met signalling promotes Notch3 activation and human vascular smooth muscle cell osteogenic differentiation in vitro. Atherosclerosis 2011;219:440-7.