Disease relevance of Gusperimus

• Effects of 15-deoxyspergualin on experimental autoimmune giant cell myocarditis of the rat [1].
• The deoxyspergualin derivative LF 15-0195 has demonstrated some efficacy in animal models of autoimmune and graft-versus-host diseases and is currently tested in clinics [2].
• A new antibiotic, deoxyspergualin (DSG), demonstrated antitumor activity against L1210 leukemia in mice [3].
• Deoxyspergualin (DSG) is a potent immunosuppressive agent that is currently undergoing clinical trials for treatment of transplant rejection, preventive of human anti-mouse Ab response, and blocking autoimmune disease progression [4].
• 15-Deoxyspergualin (DSG) strongly inhibited growth of mouse EL-4 lymphoma cells in vitro and in vivo [5].

High impact information on Gusperimus

• Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins [6].
• The immunosuppressant 15-deoxyspergualin [correction of 1,5-deoxyspergualin] reveals commonality between preT and preB cell differentiation [7].
• Finally, treatment with deoxyspergualin, an inhibitor of NF-kappa B translocation, together with costimulation blockade, synergistically impairs memory T cell activation and promotes antigen-specific tolerance of memory [8].
• These newer agents include FK506, which is undergoing extensive clinical trials, rapamycin, RS-61443 and deoxyspergualin [9].
• Deoxyspergualin for liver graft rejection [10].

Chemical compound and disease context of Gusperimus

• Cross-resistance of drug-resistant murine leukemias to deoxyspergualin (NSC 356894) in vivo [11].
• The results indicated that P388 leukemia resistant to cisplatin (P388/DDPt) was cross-resistant to deoxyspergualin [11].
• However, the extent of graft coronary arteriosclerosis in the 15-Deoxyspergualin-treated group was significantly less than that seen in the cyclosporine-treated group (1.11 +/- 0.34 versus 1.71 +/- 0.24, p < 0.01) [12].
• We report a case of cyclosporin- and methylprednisolone-resistant intestinal acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation which responded to a new immunosuppressant, 15-deoxyspergualin (DSG) [13].
• To compare the therapeutic effect of 15-deoxyspergualin with that of methylprednisolone on advanced lupus nephropathy of New Zealand black/white F1 hybrid (B/W) mice, and also to study the possible synergistic effect of both drugs, B/W mice were heminephrectomized at 32 weeks of age, and were divided into six groups [14].

Biological context of Gusperimus

• Effects of immunosuppressants, FK506, deoxyspergualin, and cyclosporine A on immature human hematopoiesis [15].
• Phase I clinical and pharmacological study of suppression of human antimouse antibody response to monoclonal antibody L6 by deoxyspergualin [16].
• Clinical pharmacology of deoxyspergualin in patients with advanced cancer [17].
• In this study, we examined the immunosuppressive mechanism of the drug 15-deoxyspergualin (DSG), which has shown efficacy in the enhancement of graft survival and in the treatment of autoimmunity [18].
• Immunosuppressant deoxyspergualin inhibits antigen processing in monocytes [19].

Anatomical context of Gusperimus

• Effects of the immunosuppressants, FK506, deoxyspergualin (DSG), and cyclosporine A (CsA) on the growth of human hematopoietic progenitor cells were tested in the presence of interleukin-3 (IL-3) with purified bone marrow and blood cells as targets in methylcellulose culture [15].
• Furthermore, deoxyspergualin reduced Ag presentation by macrophages in relation to the amount of HSC73 expressed in these cells [20].
• The operational tolerance induction protocol combined peritransplant anti-CD3 immunotoxin to deplete T-cells and 15-deoxyspergualin to arrest proinflammatory cytokine production and maturation of dendritic cells [21].
• The effect of 15-Deoxyspergualin, a novel drug which has been described to have anti-tumour activity, on allogeneic graft survival (Dark Agouti----Lewis rats) after pancreatic islet transplantation was tested [22].
• This study examined whether deoxyspergualin can modulate the mesangial cell response to glomerular injury [23].

Associations of Gusperimus with other chemical compounds

• We induced donor-specific tolerance in a fully MHC-mismatched murine model of cardiac transplantation by simultaneously targeting T cell and DC function using anti-CD45RB mAb and LF 15-0195, a novel analog of the antirejection drug 15-deoxyspergualin, respectively [24].
• Transplantations were performed in untreated mice and mice immunosuppressed with cyclosporine A (CsA) plus 15-deoxyspergualin (DSG) [25].
• Mycophenolic acid, sirolimus and gusperimus may impair bone marrow function and this adverse effect may be enhanced by concomitant administration of other myelosuppressive drugs [26].
• Treatment with deoxyspergualin, an hsc70 inhibitor, sensitized K562 cells to complement lysis, whereas treatment with ethanol, butanol or hemin, inducers of hsc70 synthesis, protected the cells from complement-mediated lysis [27].
• Prevention of type I diabetes in the non-obese diabetic (NOD) mouse with 15-deoxyspergualin (15-DS) or 15-DS + cyclosporin A (CyA) [28].

Gene context of Gusperimus

• The effects of 4-phenylbutyrate and deoxyspergualin, described previously to interfere with Hsp70 binding, were also tested upon CFTR degradation and processing [29].
• Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells [30].
• In vivo effects of the immunosuppressant 15-deoxyspergualin on hematopoiesis in murine allogeneic bone marrow chimeras. Its thrombopoietic activity and reversal of adverse effects with granulocyte colony-stimulating factor and/or erythropoietin [31].
• Although deoxyspergualin appears to exert its immunosuppressive effect via a mechanism similar to that of cyclosporin A and FK506, it does not share their ability to modify Pgp-mediated multidrug resistance [32].
• Immunosuppressant 15-deoxyspergualin (DSG) inhibited induction of inducible nitric oxide synthase (iNOS) following stimulation with IFN-gamma and LPS in a cultured macrophage cell line, J774A.1 [corrected] [33].

Analytical, diagnostic and therapeutic context of Gusperimus

• Insulin independence in type I diabetes after transplantation of unpurified islets from single donor with 15-deoxyspergualin [34].
• All patients received standard immunosuppression and, at ICC transplantation, antithymocyte globulin or 15-deoxyspergualin [35].
• The effects of a new immunosuppressant agent, 15-deoxyspergualin (DSG), on rats with experimental autoimmune myocarditis (EAM), an animal model of human giant cell myocarditis, were examined [1].
• Brief peritransplant treatment of multiple nonhuman primates (NHP) with anti-CD3 immunotoxin and deoxyspergualin has induced stable (5-10 years) rejection-free tolerance to MHC-mismatched allografts, which associated with sustained elevations in serum IL-10 [36].
• Prolongation of graft survival in allogeneic islet transplantation by (-) 15-deoxyspergualin in the rat [22].

References