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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
Structure of TRESPERIMUS

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)

HIDE SMILES / InChI

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.

Approval Year

PubMed

PubMed

TitleDatePubMed
LF 08-0299 protects murine recipients of minor antigen disparate donor marrow from lethal graft-versus-host disease.
1995 Dec 29
LF 08-0299 induces tolerance after short-term treatment in a fully major histocompatibility mismatched rat cardiac allograft model.
1995 Feb
Both CD45RC+ and negative CD4+ suppressor cells are present in the rat cardiac allograft LF 08-0299-induced tolerance model.
1997 Feb-Mar
T cell repertoire expression in murine recipients of bone marrow transplant after LF 08-0299 (Tresperimus) administration.
1998 Dec
LF 08-0299 in the prophylaxis and treatment of chronic rejection in a rat aortic allograft model.
2000
Tresperimus: a new agent for transplant tolerance induction.
2001 Jul
Involvement of semicarbazide-sensitive amine oxidase in tresperimus metabolism in human and in rat.
2001 May
Effect of tresperimus on ex vivo expansion of CD34+CD38(-)-enriched cord blood cells.
2002
Novel pharmacotherapeutic approaches to prevention and treatment of GVHD.
2002
Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO).
2002 Dec
In vitro metabolism of tresperimus by human vascular semicarbazide-sensitive amine oxidase.
2002 Jun
Protective effect of intravitreal administration of tresperimus, an immunosuppressive drug, on experimental autoimmune uveoretinitis.
2011 Jul 20
Patents

Patents

Substance Class Chemical
Created
by admin
on Fri Dec 15 15:32:16 GMT 2023
Edited
by admin
on Fri Dec 15 15:32:16 GMT 2023
Record UNII
286F595V8H
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRESPERIMUS
INN  
INN  
Official Name English
LF-08-0299
Code English
LF 08-0299
Code English
tresperimus [INN]
Common Name English
CARBAMIC ACID, (4-((3-AMINOPROPYL)AMINO)BUTYL)-, 2-((6-((AMINOIMINOMETHYL)AMINO)HEXYL)AMINO)-2-OXOETHYL ESTER
Systematic Name English
CARBAMIC ACID, N-(4-((3-AMINOPROPYL)AMINO)BUTYL)-, 2-((6-((AMINOIMINOMETHYL)AMINO)HEXYL)AMINO)-2-OXOETHYL ESTER
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C574
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
Code System Code Type Description
INN
7522
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
FDA UNII
286F595V8H
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
EPA CompTox
DTXSID50166968
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
MESH
C092303
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
ChEMBL
CHEMBL98034
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
NCI_THESAURUS
C66626
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
EVMPD
SUB11241MIG
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
PUBCHEM
3086680
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
SMS_ID
100000077505
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
CAS
160677-67-8
Created by admin on Fri Dec 15 15:32:16 GMT 2023 , Edited by admin on Fri Dec 15 15:32:16 GMT 2023
PRIMARY
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