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
Significant effect of HLA-DRB1 matching on acute rejection of kidney transplants within 3 months.	2001 Feb-Mar	11267248
Pretreatment of HL60 cells with Deoxyspergualin enhances trail-induced apoptosis independent of caspase 3 activation.	2001 Feb-Mar	11266818
Identification of an inhibitor of hsc70-mediated protein translocation and ATP hydrolysis.	2001 Jan 12	11036084
New developments in the prophylaxis and treatment of graft versus host disease.	2001 Jul	11583062
Treatment of transplant rejection: are the traditional immunosuppressants good enough?	2001 Mar	11575705
Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis.	2001 Mar	11224696
Immunosuppression in ANCA-associated vasculitis.	2001 May	11377509
Phenotypic and functional analysis of T-cell recovery after anti-CD3 immunotoxin treatment for tolerance induction in rhesus macaques.	2001 May	11334671
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
Treatment with immunotoxin.	2001 May 29	11375071
15-Deoxyspergualin protects the islet graft from macrophage-mediated injury.	2002 Aug	12176438
Short-term prophylaxis with deoxyspergualin prevents testicular autoimmunity in mice.	2002 Aug 23	12206860
Inhibition of cell growth through inactivation of eukaryotic translation initiation factor 5A (eIF5A) by deoxyspergualin.	2002 May 1	11964177
Cytoprotective effect of hepatic cell pretreatment with 15-deoxyspergualin to prevent warm ischemic reperfusion injuries in rats.	2002 Nov	12431570
Immunosuppressive drugs in islet xenotransplantation: a tool for gaining further insights in the mechanisms of the rejection process.	2002 Oct 27	12438951
Inhibition of CTP: phosphocholine cytidylyltransferase activity by 15-deoxyspergualin.	2003 Aug	14563164
Stable alpha- and beta-islet cell function after tolerance induction to pancreatic islet allografts in diabetic primates.	2003 Feb	12603208
15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy.	2003 Feb	12538745
Prophylactic deoxyspergualin treatment in living-related renal-transplant recipients transfused with donor-specific blood.	2003 Jan 15	12544872
Heterologous immunity provides a potent barrier to transplantation tolerance.	2003 Jun	12813024
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
Syenergistic effect of 15-deoxyspergualin with costimulation blockade on alloimmune response.	2004 Oct	15561275
Induction of tolerance to composite tissue allograft in a rat model.	2006	17091475
The molecular chaperone hsp70 interacts with the cytosolic II-III loop of the Cav2.3 E-type voltage-gated Ca2+ channel.	2006	16543726
In vivo effects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis.	2006 Dec	17100765
Beneficial effects of simultaneous treatment with 15-deoxyspergualin and monoclonal antibodies to CD45RB and CD154 on murine islet transplantation recipients.	2006 Jul 27	16858281
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
15-deoxyspergualin inhibits eukaryotic protein synthesis through eIF2alpha phosphorylation.	2007 Jan 15	16952278
15-deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum.	2007 Mar 2	17194705
Chemical conjugation of DeltaF508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl- channel functions.	2008 Aug	18515409
Deoxyspergualin in relapsing and refractory Wegener's granulomatosis.	2009 Jul	18713783
Plasmodial heat shock proteins: targets for chemotherapy.	2010 Feb	20041948

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