Delmitid
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| Non-proprietary name | Delmitid | |||||||||
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| Molecular formula | C 59 H 105 N 17 O 11 | |||||||||
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| Molar mass | 1228.57 g · mol -1 | |||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||
Delmitid is an experimental drug that artificially suppresses the immune system ( immunosuppressant ) and is being developed for the treatment of various diseases and in the area of organ transplants . The peptide is a product of Procter & Gamble and Genzyme and was previously developed by SangStatMedical.
Delmitid is an orally administered, acid-stable, topically active peptide which is being developed in phase II / III in the indications of chronic inflammatory bowel disease ( ulcerative colitis , Crohn's disease ), chemotherapy-associated intestinal toxicity, dermatitis and to suppress immune reactions after organ transplantation. In the case of systemic application, the indications SIRS , sepsis , multiple organ failure and COPD are to be assumed, although no studies are yet available. Delmitid inhibits HIV - replication , the mechanism remains unclear.
Working principle
Delmitid has two working principles. As a direct inhibitor , it leads to a paradoxically increased activity of heme oxygenase , which is generated from heme , carbon monoxide (CO) and bilirubin and thus has an immunosuppressive and protective effect on the small blood vessels. As a presumed inhibitor of the myd88-irak-traf6 primary complex, it inhibits the signal transduction of various toll-like receptors and of interleukin-1 (IL-1) and thus the consecutive effects (activation of the nuclear factor κB (NF-κB), p38-mitogen-activated systems Protein kinase (p38MAPK), tristetraprolin and the mRNA stability of various cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), interleukin-6 (IL-6) and gamma interferon (IFN-γ).
Discovery story
Delmitid has an unusual history of discovery. Some human leukocyte antigen molecules (HLA) have special immunoregulatory properties that lead to statistical associations with certain diseases (example: all members of a submarine crew suffered salmonella poisoning , but only those who were HLA-B27-positive developed reactive arthritis ). In the early 1990s, individual peptide fragments of various HLA molecules were examined for particular immunological effects. It was recognized that a decapeptide of HLA-B27 could inhibit the mixed lymphocyte reaction . Without knowing the actual pharmacological goal, a battery of functionally similar peptides was generated and evaluated in manageable systems. A peptide was developed which is published under the names RDP-58, RDP-1258, Allotrap-1258 and has the sequence N-Arg-Nle-Nle-Nle-Arg-Nle-Nle-Nle-Gly-Tyr-C , where Nle means [norleucine]. Conducting property is the ability to inhibit TNF alpha production.
literature
- Birgit Schäfer: Analysis of new therapeutic strategies for the inhibition of the human immunodeficiency virus type 1 . Dissertation, Hamburg 2006, urn : nbn: de: gbv: 18-29914
Individual evidence
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ CG De Vry, M Valdez, M Lazarov et al .: Topical application of a novel immunomodulatory peptide, RDP58, reduces skin inflammation in the phorbol ester-induced dermatitis model . In: Journal of Investigative Dermatology . 125, No. 3, September 2005, pp. 473-481. PMID 16117788 . Retrieved June 10, 2010.
