| Immunotherapeutic and antitumour potential of thalidomide analogues. | |
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MedLine Citation:
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PMID: 11727503 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The immunomodulatory drug thalidomide has been shown to be clinically useful in a number of conditions including various immunological disorders and cancers. Clinical activity in vivo is attributed to the wide ranging immunological and non-immunological properties possessed by this drug; these include anti-TNF-alpha, T-cell co-stimulatory, anti-angiogenic activities and also direct antitumour activity. Recently, the design of compounds based on the thalidomide structure has led to the synthesis of analogues with greatly enhanced immunological activity and with similarly decreased toxicity. These derivatives fail into at least two categories; selective cytokine inhibitory drugs (SelCID), which are phosphodiesterase Type 4 (PDE4) inhibitors and immunomodulatory drugs (IMiD), similar to thalidomide which act via unknown mechanism(s). These compounds are in the process of being characterised in laboratory studies and are also now being assessed in Phase I and Phase I/II clinical studies. In this review we will highlight the properties of these two novel classes of compound in terms of their effects on both immunological and non-immunological systems in vitro. We will also describe how these studies are enabling the characterisation and development of these compounds into clinically relevant drugs in widely varying diseases. To this end we will describe the various clinical studies of lead compounds that are in progress and speculate as to the potential and future development of these exciting compounds. |
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Authors:
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J B Marriott; G Muller; D Stirling; A G Dalgleish |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Expert opinion on biological therapy Volume: 1 ISSN: 1471-2598 ISO Abbreviation: Expert Opin Biol Ther Publication Date: 2001 Jul |
Date Detail:
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Created Date: 2001-11-30 Completed Date: 2002-02-06 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101125414 Medline TA: Expert Opin Biol Ther Country: England |
Other Details:
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Languages: eng Pagination: 675-82 Citation Subset: IM |
Affiliation:
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Division of Oncology, Department of Cellular & Molecular Sciences, St George's Hospital Medical School, Cranmer Terrace, London, UK. jmarriot@sghms.ac.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3',5'-Cyclic-AMP Phosphodiesterases
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antagonists & inhibitors Antineoplastic Agents / chemistry, immunology, therapeutic use* Clinical Trials as Topic Cyclic Nucleotide Phosphodiesterases, Type 4 Cytokines / metabolism Humans Immunosuppressive Agents / chemistry, immunology, therapeutic use* Molecular Structure Neoplasms / drug therapy* Thalidomide / analogs & derivatives*, immunology, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Cytokines; 0/Immunosuppressive Agents; 50-35-1/Thalidomide; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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