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Details

Stereochemistry ACHIRAL
Molecular Formula C17H37N7O3.3ClH
Molecular Weight 496.904
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRESPERIMUS TRIHYDROCHLORIDE

SMILES

Cl.Cl.Cl.NCCCNCCCCNC(=O)OCC(=O)NCCCCCCNC(N)=N

InChI

InChIKey=ROUJFTXNBSKUBV-UHFFFAOYSA-N
InChI=1S/C17H37N7O3.3ClH/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);3*1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
LF 08-0299 protects murine recipients of minor antigen disparate donor bone marrow from lethal graft-versus-host disease.
1996 Dec
Tolerance in a rat cardiac allograft model after short-term treatment with LF 08-0299. Absence of clonal deletion and evidence of CD4+ suppressor cells.
1996 Dec 15
Prevention of lethal graft-versus-host disease following allogeneic bone marrow transplantation in mice by short course administration of LF 08-0299.
1996 Sep 27
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
Tresperimus. LF 080299.
1999 Jan
Analysis of in vivo immunosuppressive and in vitro interaction with constitutive heat shock protein 70 activity of LF08-0299 (Tresperimus) and analogues.
1999 May
Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety.
1999 Nov 18
LF 08-0299 in the prophylaxis and treatment of chronic rejection in a rat aortic allograft model.
2000
Drug therapy for acute graft-versus-host disease prophylaxis.
2000 Jun
Effect of tresperimus on in vitro human cord blood CD34+ cell differentiation.
2001
Tresperimus: a new agent for transplant tolerance induction.
2001 Jul
New developments in the prophylaxis and treatment of graft versus host disease.
2001 Jul
Tresperimus (Laboratoires Fournier).
2001 Mar
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 15:31:31 GMT 2023
Edited
by admin
on Fri Dec 15 15:31:31 GMT 2023
Record UNII
Q98H19P60T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRESPERIMUS TRIHYDROCHLORIDE
Common Name English
CARBAMIC ACID, (4-((3-AMINOPROPYL)AMINO)BUTYL)-, 2-((6-((AMINOIMINOMETHYL)AMINO)HEXYL)AMINO)-2-OXOETHYL ESTER, TRIHYDROCHLORIDE
Systematic Name English
N-(4-((3-AMINOPROPYL)AMINO)BUTYL)-2-((6-((AMINOIMINOMETHYL)AMINO)HEXYL)AMINO)-2-OXOETHYL-CARBAMIC ACID TRIHYDROCHLORIDE
Systematic Name English
LF-08-0299 TRIHYDROCHLORIDE
Code English
Code System Code Type Description
PUBCHEM
122129926
Created by admin on Fri Dec 15 15:31:31 GMT 2023 , Edited by admin on Fri Dec 15 15:31:31 GMT 2023
PRIMARY
CAS
160678-11-5
Created by admin on Fri Dec 15 15:31:31 GMT 2023 , Edited by admin on Fri Dec 15 15:31:31 GMT 2023
PRIMARY
FDA UNII
Q98H19P60T
Created by admin on Fri Dec 15 15:31:31 GMT 2023 , Edited by admin on Fri Dec 15 15:31:31 GMT 2023
PRIMARY
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ACTIVE MOIETY