Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C17H37N7O3 |
Molecular Weight | 387.5208 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCNC(N)=N
InChI
InChIKey=IDINUJSAMVOPCM-INIZCTEOSA-N
InChI=1S/C17H37N7O3/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)/t16-/m0/s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21356124Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/27261432 | https://www.ncbi.nlm.nih.gov/pubmed/12538745 | https://www.ncbi.nlm.nih.gov/pubmed/2039989
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21356124
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/27261432 | https://www.ncbi.nlm.nih.gov/pubmed/12538745 | https://www.ncbi.nlm.nih.gov/pubmed/2039989
Deoxyspergualin is a derivative of the antitumor antibiotic spergualin, that used as an immunosuppressive drug. Deoxyspergualin shows immunosuppressive activity both in vitro and in vivo, affecting B-lymphocyte, T-lymphocyte and macrophage/monocyte function. In rodents and human cell systems, Deoxyspergualin shows a dose-dependent inhibition of primary and secondary responses to T-, B- and antigen-presenting cell-dependent reactions. Deoxyspergualin also blocks nuclear translocation of NF-kB in a pre-B-cell line, thereby affecting NF-kB driven transcription of the kappa light chain. Deoxyspergualin inhibits desoxyhypusine synthase, the first enzyme in the formation of active eukaryotic translation initiation factor 5A. This factor is important for the stabilization of certain mRNA transcripts (TNF-a and others). The immunosuppressive properties of Deoxyspergualin have been demonstrated in preclinical animal studies including Systemic lupus erythematosus models. In humans with glucocorticoidresistant kidney transplant rejection, Deoxyspergualin shows the same efficacy rate as the strongly T-cell depleting anti-CD3 monoclonal antibody. Deoxyspergualin has been licensed in Japan for acute renal allograft rejection since 1994. In 2003, an open clinical trial successfully tested Deoxyspergualin in patients with persistent ANCA-associated vasculitis. Adverse events (AE) were common but rarely led to treatment discontinuation. Against this background, Deoxyspergualin was granted an orphan drug status for the treatment of Wegener’s granulomatosis by the European Medicines Agency (EMA).
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: Q15366|||Q68Y55 Gene ID: 5094.0 Gene Symbol: PCBP2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27261432 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.1 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
2160 mg/m² 1 times / day multiple, intravenous dose: 2160 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
0.25 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
80 mg/m² 1 times / day steady-state, intravenous dose: 80 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
114 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
264 mg/m² 1 times / day multiple, intravenous dose: 264 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1164 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
2160 mg/m² 1 times / day multiple, intravenous dose: 2160 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
247 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
560 mg/m² 1 times / day multiple, intravenous dose: 560 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
280 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
720 mg/m² 1 times / day multiple, intravenous dose: 720 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
32 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
80 mg/m² 1 times / day steady-state, intravenous dose: 80 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
534 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
960 mg/m² 1 times / day unknown, intravenous dose: 960 mg/m² route of administration: Intravenous experiment type: UNKNOWN co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
72 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
160 mg/m² 1 times / day multiple, intravenous dose: 160 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
836 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
1140 mg/m² 1 times / day multiple, intravenous dose: 1140 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
260 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
400 mg/m² 1 times / day multiple, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
264 mg/m² 1 times / day multiple, intravenous dose: 264 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
30.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
2160 mg/m² 1 times / day multiple, intravenous dose: 2160 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
16.7 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
560 mg/m² 1 times / day multiple, intravenous dose: 560 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
10 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
720 mg/m² 1 times / day multiple, intravenous dose: 720 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
22 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
80 mg/m² 1 times / day steady-state, intravenous dose: 80 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
12.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
960 mg/m² 1 times / day unknown, intravenous dose: 960 mg/m² route of administration: Intravenous experiment type: UNKNOWN co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
7 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
160 mg/m² 1 times / day multiple, intravenous dose: 160 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
24.1 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
1140 mg/m² 1 times / day multiple, intravenous dose: 1140 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
37 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2039989/ |
400 mg/m² 1 times / day multiple, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
DEOXYSPERGUALIN plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
PubMed
Title | Date | PubMed |
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Pretreatment of HL60 cells with Deoxyspergualin enhances trail-induced apoptosis independent of caspase 3 activation. | 2001 Feb-Mar |
|
Treatment with immunotoxin. | 2001 May 29 |
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Isolation of mouse-to-rat cardiac xenograft-infiltrating cells by ex vivo propagation. | 2002 May |
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Effect of heat stress on lipopolysaccharide-induced vascular permeability change in mice. | 2002 Nov |
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Inhibition of CTP: phosphocholine cytidylyltransferase activity by 15-deoxyspergualin. | 2003 Aug |
|
Successful treatment of accelerated vascular rejection in a highly immunised renal transplant recipient with immunoadsorption and 15-deoxyspergualin. | 2004 Aug |
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Novel immunosuppressants. | 2004 Dec |
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[Long-term survival of a heterologously transplanted heart following daily administration of cyclosporin and short-term treatment with 15-deoxyspergualin]. | 2004 Nov |
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Results of kidney transplantation in patients receiving MMF- or MMF and basiliximab-containing immunosuppression. | 2004 Sep |
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A case of acute humoral rejection with various depositions of C4d, IgG, IgM, and C3c in peritubular capillaries and/or glomerular capillaries. | 2005 |
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Elevated T regulatory cells in long-term stable transplant tolerance in rhesus macaques induced by anti-CD3 immunotoxin and deoxyspergualin. | 2005 Dec 15 |
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Prolonged treatment of refractory Wegener's granulomatosis with 15-deoxyspergualin: an open study in seven patients. | 2005 Jun |
|
Deoxyspergualin prophylaxis with tacrolimus further improves long-term graft survival in living-related renal-transplant recipients transfused with donor-specific blood. | 2005 Mar |
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Safety of 15-deoxyspergualin in the treatment of glomerulonephritis associated with active systemic lupus erythematosus. | 2005 Oct |
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Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. | 2005 Oct 27 |
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Induction of tolerance to composite tissue allograft in a rat model. | 2006 |
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The molecular chaperone hsp70 interacts with the cytosolic II-III loop of the Cav2.3 E-type voltage-gated Ca2+ channel. | 2006 |
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In vivo effects of cyclic administration of 15-deoxyspergualin on leucocyte function in patients with Wegener's granulomatosis. | 2006 Dec |
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15-Deoxyspergualin and cyclophosphamide, but not mycophenolate mofetil, prolong survival and attenuate renal disease in a murine model of ANCA-associated crescentic nephritis. | 2006 Jan |
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Beneficial effects of simultaneous treatment with 15-deoxyspergualin and monoclonal antibodies to CD45RB and CD154 on murine islet transplantation recipients. | 2006 Jul 27 |
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Vasculitis treatment - new therapeutic approaches. | 2006 Jun |
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Usage of deoxyspergualin on steroid-resistant acute rejection in living donor liver transplantation. | 2006 Mar |
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15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function. | 2006 Sep 22 |
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15-deoxyspergualin prevents mucosal injury by inhibiting production of TNF-alpha and down-regulating expression of MD-1 in a murine model of TNBS-induced colitis. | 2007 Aug |
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Control of cyclosporine A-induced tumor progression using 15-deoxyspergualin for rat cardiac transplantation. | 2007 Aug 15 |
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Steroid-resistant late acute rejection after a living donor liver transplantation: case report and review of the literature. | 2007 Feb |
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15-deoxyspergualin inhibits eukaryotic protein synthesis through eIF2alpha phosphorylation. | 2007 Jan 15 |
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Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients. | 2007 Jul-Aug |
|
15-deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum. | 2007 Mar 2 |
|
Chemical conjugation of DeltaF508-CFTR corrector deoxyspergualin to transporter human serum albumin enhances its ability to rescue Cl- channel functions. | 2008 Aug |
|
Maintaining remission in a patient with vasculitis. | 2008 Sep |
|
Evaluation of the ameliorative effects of immunosuppressants on crescentic glomerulonephritis in SCG/Kj mice. | 2008 Sep |
|
Deoxyspergualin in relapsing and refractory Wegener's granulomatosis. | 2009 Jul |
|
Polyamine compound deoxyspergualin inhibits heat shock protein-induced activation of immature dendritic cells. | 2009 Mar |
|
Plasmodial heat shock proteins: targets for chemotherapy. | 2010 Feb |
|
Clinicopathological analysis of acute vascular rejection cases after renal transplantation. | 2010 Jul |
|
Reduction of MPO-ANCA epitopes in SCG/Kj mice by 15-deoxyspergualin treatment restricted by IgG2b associated with crescentic glomerulonephritis. | 2010 Jul |
|
Long-term treatment of relapsing Wegener's granulomatosis with 15-deoxyspergualin. | 2010 Mar |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2039989
The dosage range explored was 80 to2160 mg/m^2/day for 5 days by continuous i.v. infusion.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1690194
Antibody production to DNP-LPS was performed by incubating BALB/c mouse spleen cells (5 x 10^6/ml) with 20mkg/ml of DNP-LPS in complete serum free medium, S-clone SF-H for 120 hours. Anti-DNP-IgM in the supernatant was measured by EIA. In vitro effect of DSG and MeDSG on mitogenic response to LPS was assessed. DSG and MeDSG inhibited the mitogenic response over the concentration of 1.0 to 0.1 mkg/ml. The maximum inhibition observed was 60~70% suppression relative to control levels at a dose of 100mkg/ml.
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DTXSID70237548
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91272
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89149-10-0
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57F9XM233R
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DB12991
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)