GUSPERIMUS TRIHYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H37N7O3.3ClH
Molecular Weight	496.904
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of GUSPERIMUS TRIHYDROCHLORIDE

Structure Search

SMILES

Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCNC(N)=N

InChI

InChIKey=AXSPHUWXYSZPBG-UHFFFAOYSA-N

InChI=1S/C17H37N7O3.3ClH/c18-9-7-11-21-10-5-6-12-22-15(26)16(27)24-14(25)8-3-1-2-4-13-23-17(19)20;;;/h16,21,27H,1-13,18H2,(H,22,26)(H,24,25)(H4,19,20,23);3*1H

HIDE SMILES / InChI

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2010/01/WC500065437.pdf
Curator's Comment: description was created based on several sources, including, www.ncbi.nlm.nih.gov/pubmed/24501242

Gusperimus is an antibiotic, isolated from cultures of the soil commensal Bacillus laterosporus. It possess immunosuppressive properties and exerts its effect through binding to heat shock proteins Hsp90 and Hsc70. Although initially, the drug was being investigated for the treatment of cancer, it recieved orphan designation for the treatment of refractory Wegener’s granulomatosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11964177	Binding Agent 1064
Heat shock 70 kDa protein 1A 4 Target ID: P0DMV8 Gene ID: 3303\|\|\|3304 Gene Symbol: HSPA1A Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/11964177	Binding Agent 1064
Heat shock 70 kDa protein 1B 3 Target ID: P0DMV9 Gene ID: 3303\|\|\|3304 Gene Symbol: HSPA1B Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/11964177	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Wegener’s granulomatosis 5 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2010/01/WC500065437.pdf	Primary		Approved 8429	SPANIDIN Approved Use Spanidin (0.5 mg/kg body weight (BW)) is indicated as therapy for induction of remission in adult patients suffering from refractory Wegener’s granulomatosis, unresolved by standard treatment with cyclophosphamide and glucocorticoids according to EULAR recommendations. Launch Date 2001

PubMed

Title	Date	PubMed
Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias.	2000 May	10815900
Identification of an inhibitor of hsc70-mediated protein translocation and ATP hydrolysis.	2001 Jan 12	11036084
Immunosuppression in ANCA-associated vasculitis.	2001 May	11377509
Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules.	2001 May 18	11278929
STEALTH in transplantation tolerance.	2002	12403353
Inhibition of cell growth through inactivation of eukaryotic translation initiation factor 5A (eIF5A) by deoxyspergualin.	2002 May 1	11964177
Inhibition of CTP: phosphocholine cytidylyltransferase activity by 15-deoxyspergualin.	2003 Aug	14563164
Effect of plasma exchange in combination with deoxyspergualin on the survival of guinea-pig hearts in macrophage-depleted C6-deficient rats.	2003 May	12694541
Both T and non-T cells with proliferating potentials are effective in inducing suppression of allograft responses by alloantigen-specific intravenous presensitization combined with suboptimal doses of 15-deoxyspergualin.	2004 Jun-Jul	15203125
[Long-term survival of a heterologously transplanted heart following daily administration of cyclosporin and short-term treatment with 15-deoxyspergualin].	2004 Nov	15675301
Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac xenotransplantation.	2004 Oct	15561287
A case of acute humoral rejection with various depositions of C4d, IgG, IgM, and C3c in peritubular capillaries and/or glomerular capillaries.	2005	15955172
Combined therapy of deoxyspergualin and plasmapheresis: a useful treatment for antibody-mediated acute rejection after kidney transplantation.	2005 Mar	15848578
In vivo effects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis.	2006 Dec	17100765
15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function.	2006 Sep 22	16884692
Steroid-resistant late acute rejection after a living donor liver transplantation: case report and review of the literature.	2007 Feb	17287604
Chemical conjugation of DeltaF508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl- channel functions.	2008 Aug	18515409
Differential promotion of hematopoietic chimerism and inhibition of alloreactive T cell proliferation by combinations of anti-CD40Ligand, anti-LFA-1, everolimus, and deoxyspergualin.	2008 Nov	18675355
Polyamine compound deoxyspergualin inhibits heat shock protein-induced activation of immature dendritic cells.	2009 Mar	18686015
Clinicopathological analysis of acute vascular rejection cases after renal transplantation.	2010 Jul	20590689

Patents

Sample Use Guides

In Vivo Use Guide

0.5 mg/kg body weight (BW)

Route of Administration: Intravascular

In Vitro Use Guide

To test whether Gusperimus influences the proloferative response of human B-cells, the cells were cultured on CDw32L with 1 ug/ml anti-CD40 mAb with or without IL-10 (100 ng/ml), IL-2 (500 U/ml) or IL-4 (500 U/ml) for 7 days. The drug was added at concentration of 0.2-200 ug/ml. The drug inhibited the prolifirative response of anti-CD40 stimulated B lymphocytes. The inhibition varied among cultures from 48% to 85% at 200 ug/ml.

Name

Type

Language

GUSPERIMUS TRIHYDROCHLORIDE

Official Name

English

NKT-01

Code

English

BMS-181173

Code

English

SPANIDIN

Brand Name

English

GUSPERIMUS HYDROCHLORIDE [JAN]

Common Name

English

GUSPERIMUS HYDROCHLORIDE

Common Name

English

BMY-42215-1

Code

English

Gusperimus hydrochloride [WHO-DD]

Common Name

English

GUSPERIMUS HYDROCHLORIDE [MART.]

Common Name

English

GUSPERIMUS TRIHYDROCHLORIDE [MI]

Common Name

English

HEPTANAMIDE, 7-((AMINOIMINOMETHYL)AMINO)-N-(2-((4-((3-AMINOPROPYL)AMINO)BUTYL)AMINO)-1-HYDROXY-2-OXOETHYL)-, TRIHYDROCHLORIDE, (±)-

Common Name

English

NSC-356894

Code

English

HEPTANAMIDE, 7-((AMINOIMINOMETHYL)AMINO)-N-(2-((4-((3-AMINOPROPYL)AMINO)BUTYL)AMINO)-1-HYDROXY-2-OXOETHYL)-, HYDROCHLORIDE (1:3)

Systematic Name

English

GUSPERIMUS TRIHYDROCHLORIDE [USAN]

Common Name

English

(±)-N-(((4-((3-AMINOPROPYL)AMINO)BUTYL)CARBAMOYL)HYDROXYMETHYL)-7-GUANIDINOHEPTANAMIDE TRIHYDROCHLORIDE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

342711