Cilengitide Merck

Current Opinion in Investigational Drugs

Volumn 4, Issue 6, 2003, Pages 741-745

  Smith, Jeffrey W ^a  

^a BURNHAM INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHAVBETA3 INTEGRIN ANTAGONIST; ANTINEOPLASTIC AGENT; CILENGITIDE; EMD 58189; GEMCITABINE; MONOCLONAL ANTIBODY LM 609; UNCLASSIFIED DRUG;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; BLOOD TOXICITY; CLINICAL TRIAL; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CONTRAINDICATION; DRUG EFFECT; DRUG ERUPTION; DRUG MECHANISM; DRUG METABOLISM; DRUG SYNTHESIS; DRUG TOLERABILITY; DRUG TOXICITY; FATIGUE; GLIOBLASTOMA; HUMAN; LUNG NON SMALL CELL CANCER; MONOTHERAPY; NAUSEA; NONHUMAN; PANCREAS CANCER; PRURITUS; REVIEW; STRUCTURE ACTIVITY RELATION; VOMITING;

ANGIOGENESIS INHIBITORS; ANIMALS; CLINICAL TRIALS; DRUGS, INVESTIGATIONAL; HUMANS; NEOPLASMS; SNAKE VENOMS; TECHNOLOGY, PHARMACEUTICAL;

EID: 0042165828     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (29)

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7. 338085 N-methylated cyclic RGD peptides as highly active and selective αvβ3integrin antagonists. Dechantsreiter MA, Planker E, Matha B, Lohof E, Holzemann G, Jonczyk A, Goodman SL, Kessler H J Med Chem 1999 42 16 3033-3040
8. 349973 Progress in oncology: Angiogenesis inhibitor EMD-121974 enters new phase I and II clinical trials in Europe and the US. Merck KGaA Press Release 1999 December 09
9. 363537 NCI Cancer Trials: Anti-angiogenesis inhibitors in clinical trials. National Cancer Institute Company World Wide Web Site 2000 April 19 Details of a clinical study of EMD-121974 in an NCI-sponsored phase I, dose-escalation trial in 31 to 40 patients with advanced or metastatic cancer. Patients are to receive EMD-121974 iv over 1 h twice weekly for 4 weeks, with treatment continuing for an additional course in the absence of unacceptable toxicity, and patients with stable or responding disease able to continue the therapy indefinitely until disease progression. Cohorts of three to six patients will receive escalating doses of EMD-121974 until the MTD is determined.
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14. 413957 R&D presentation. Merck KGaA Company Communication 2001 June 29
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16. 440821 Drug development pipeline: BLP-25, cilengitide. Merck KGaA Company Communication 2002 February 21 The Scripps Institute was collaborating with Merck in the preclinical development of cilengitide but is not involved in clinical trials. Merck is conducting phase II trials of cilengitide in NSCLC and pancreatic cancer patients. In addition, the NCI is sponsoring a phase I and a phase I/II trial in brain cancer.
17. 443483 Nanomolecular small molecule inhibitors for α-v-β-6, α-v-β-5, and α-v-β-3 integrins. Goodman SL, Holzemann G, Sulyok GAG, Kessler H J Med Chem 2002 45 5 1045-1051
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19. 467737 Autumn press conference 2002. Merck KGaA Company Presentation 2002 October 24
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21. 476332 Integrins: Bidirectional, allosteric signalling machines. Hynes RO Cell 2002 110 6 673-687
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23. 476337 A peptidomimetic antagonist of the integrin αvβ3 inhibits Leydig cell tumor growth and the development of hypercalcemia of malignancy. Carron CP, Meyer DM, Pegg JA, Engelman VW, Nickols MA, Settle SL, Westlin WF, Ruminski PG, Nickols GA Cancer Res 1998 58 9 1390-1395 This paper presents the crystal structure of αvβ3 bound to cilengitide. Not only is the report essential in understanding the SAR of the compound, it is one of the most significant papers ever published on integrins.
24. 476338 Crystal structure of the extracellular segment of integrin αvβ3 in complex with an Arg-Gly-Asp ligand. Xiong JP, Stehle T, Zhang R, Joachimiak A, Frech M, Goodman SL, Amaout MA Science 2002 296 5565 151-155
25. 476340 αv-Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Taga T, Suzuki A, Gonzalez-Gomez I, Gilles FH, Stins M, Shimada H, Barsky L, Weinberg KI, Laug WE Int J Cancer 2002 98 5 690-697
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27. 476342 Enhanced pathological angiogenesis in mice lacking β3 integrin or β3 and β5 integrins. Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala Dilke KM Nat Med 2002 8 1 27-34 This report demonstrates that genetic deficiency of β3 or β5 in mice causes enhanced tumor angiogenesis. These findings are counter to findings with antagonists of the two integrins, and reveal that our understanding of the role of integrins in angiogenesis is far from complete. As a result of these unexpected findings, this report has proven to be quite provocative.
28. 477858 Drug development pipeline: Cilengitide. Merck KGaA Company Communication 2003 January 03
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