Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H37N7O3 |
Molecular Weight | 387.5208 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NCCCNCCCCNC(=O)OCC(=O)NCCCCCCNC(N)=N
InChI
InChIKey=LVBMFPUTQOHXQE-UHFFFAOYSA-N
InChI=1S/C17H37N7O3/c18-8-7-10-21-9-5-6-13-24-17(26)27-14-15(25)22-11-3-1-2-4-12-23-16(19)20/h21H,1-14,18H2,(H,22,25)(H,24,26)(H4,19,20,23)
Molecular Formula | C17H37N7O3 |
Molecular Weight | 387.5208 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Tresperimus is a new stable immunosuppressive analog of 15-deoxyspergualin (DSG) obtained by organic chemical synthesis. It was initially developed as an antitumor agent. Tresperimus has been designed to be chemically stable in aqueous solution. Tresperimus controlled alloreactivity in a fully major histocompatibility complex (MHC) mismatched rat cardiac transplant model and also induced donor-specific long-lasting unresponsiveness. Posttransplant tresperimus therapy effectively protected mice from lethal graft-versus-host disease (GVHD) in a dose-related manner. It has been shown to suppress graft rejection as efficiently as cyclosporine A. Indeed, a short course of tresperimus has similar or better effects compared to the effects of cyclosporine in bone marrow, cardiac, and skin transplant models. Prevention of rejection is related to the induction of donor-specific tolerance without affecting immunity to third-party antigens. In addition, CD4+ T-cells from tresperimus-treated animals can transfer donorspecific tolerance to naive animals, an effect not seen with cyclosporine or other traditional immunosuppressive drugs. The mechanism by which tolerance is induced is not clear. Tresperimus binds to Hsc70, a heat shock protein– chaperoned peptide that, among other effects, inhibits nuclear localization of nuclear factor (NF)-kB, which is required for CD40 and CD28 ligation signaling in antigen-presenting cells, an important early step in T-cell costimulation. Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation. Tresperimus had been in phase III clinical trial for the treatment of graft-versus-host disease. However, this development was discontinued.
Originator
Approval Year
PubMed
Title | Date | PubMed |
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LF 08-0299 protects murine recipients of minor antigen disparate donor marrow from lethal graft-versus-host disease. | 1995 Dec 29 |
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LF 08-0299 induces tolerance after short-term treatment in a fully major histocompatibility mismatched rat cardiac allograft model. | 1995 Feb |
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Both CD45RC+ and negative CD4+ suppressor cells are present in the rat cardiac allograft LF 08-0299-induced tolerance model. | 1997 Feb-Mar |
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T cell repertoire expression in murine recipients of bone marrow transplant after LF 08-0299 (Tresperimus) administration. | 1998 Dec |
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LF 08-0299 in the prophylaxis and treatment of chronic rejection in a rat aortic allograft model. | 2000 |
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Tresperimus: a new agent for transplant tolerance induction. | 2001 Jul |
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Involvement of semicarbazide-sensitive amine oxidase in tresperimus metabolism in human and in rat. | 2001 May |
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Effect of tresperimus on ex vivo expansion of CD34+CD38(-)-enriched cord blood cells. | 2002 |
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Novel pharmacotherapeutic approaches to prevention and treatment of GVHD. | 2002 |
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Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO). | 2002 Dec |
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In vitro metabolism of tresperimus by human vascular semicarbazide-sensitive amine oxidase. | 2002 Jun |
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Protective effect of intravitreal administration of tresperimus, an immunosuppressive drug, on experimental autoimmune uveoretinitis. | 2011 Jul 20 |
Patents
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:32:16 GMT 2023
by
admin
on
Fri Dec 15 15:32:16 GMT 2023
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Record UNII |
286F595V8H
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C574
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DTXSID50166968
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C092303
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CHEMBL98034
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C66626
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