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Chemical Compound Review

Abrammune     (3S,6S,9S,12R,15S,18S,21S,24S, 30S,33S)-30...

Synonyms: Imusporin, Arpimune ME, Zinograf ME, Debio088, Papilock Mini, ...
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Disease relevance of Neoral

  • Additionally, FC/CE levels were measured in rat renal cortex either 10 days after CSA or tacrolimus therapy, or 48 hours after induction of nephrotoxic serum nephritis [1].
  • Furthermore, whether subacute/insidious tubular injury [eg, cyclosporine A (CSA), tacrolimus toxicity], nontubular injury (eg, acute glomerulonephritis), or physiological stress (eg, mild dehydration) impact renal cholesterol homeostasis have not been addressed [1].
  • In this system, cyclosporine A (CsA), although effective in suppressing SEB toxicity, fails to counteract the lethal effect of LPS [2].
  • Renal transplant patients immunosuppressed with cyclosporine A (CsA) exhibit both a significant bone loss and an increased rate of bone fractures [3].
  • In an established Candida albicans murine keratitis model, combination therapy with ophthalmic preparations of fluconazole and cyclosporine A (CsA) demonstrated in vivo drug synergy and effectively resolved wild-type C. albicans infection more rapidly than monotherapy with either drug [4].

High impact information on Neoral

  • In contrast, trisomy 8 developed in patients with good hematologic responses who often required chronic immunosuppression with cyclosporine A (CsA), and survival was excellent [5].
  • Cross-linking of peptide to cyclophilin was inhibited by CsA [6].
  • This protein, a peptidyl-prolyl cis-trans isomerase, is the yeast homologue of the protein that mediates the immunosuppressant effects of the drug cyclosporin A (CsA) [6].
  • BaxBH3Ant and Bcl2BH3Ant caused a mitochondrial membrane permeabilization (MMP) and apoptosis, via a mechanism that was not inhibited by overexpressed Bcl-2 or Bcl-X(L), yet partially inhibited by cyclosporin A (CsA), an inhibitor of the mitochondrial permeability transition pore [7].
  • When added to isolated mitochondria, BaxBH3 and Bcl2BH3 induced MMP, which was inhibited by CsA [7].

Chemical compound and disease context of Neoral


Biological context of Neoral

  • A short course of FK 506 and cyclosporin A (CsA), had conferred a negative effect on gene expression [11].
  • Calcineurin, the target of CsA, was also found to contribute to pathogenicity [4].
  • CONCLUSION: These findings indicate that steroids interfere with MPA bioavailability, and that discontinuation of the drug results in higher MPA exposure, which may compensate at least in part for the lower immunosuppressive level achieved with the remaining dual therapy with CsA and MMF [12].
  • Since cyclosporine A (CsA) may interfere with MPA pharmacokinetics, MPA and CsA also were measured in an additional control group of 12 kidney transplant patients at month 21 post-Tx who were still on triple therapy (MMF, CsA and steroids) [12].
  • Cyclosporin A (CsA) and FK506, inhibitors of T cell proliferation, have been very useful for preventing autoimmune and inflammatory disease and graft rejection [13].

Anatomical context of Neoral

  • Glutamine significantly dissipated the DeltaPsi(m) in astrocytes as demonstrated by a decrease in mitochondrial TMRE fluorescence, a process that was blocked by CsA [14].
  • Thus, pronounced vascular leukostasis, vasculitis, and T-cell and monocyte infiltration of the tubulointerstitium led to a severe damage of the allograft under therapy with CyA and NOS-B [15].
  • This system consists of stimulation of human lymphocytes with a primary mitogen (anti-T-cell receptor complex antibodies (OKT3 or wt31)) and treatment with a primary immunosuppressive drug (ISD) (Cyclosporine A (CsA) or FK-506)) [16].
  • Here we demonstrate that the inhibition of calcineurin (Cn) by using cyclosporine A (CsA) increases osteoblast differentiation, both in vivo and in vitro [17].
  • While PSC 833 and CsA had no effect on the cytotoxicity, accumulation and retention of MIT in the parent K562 cells, PSC 833 and CsA restored accumulation and retention of MIT in K562/D1-9 cells dose-dependently [18].

Associations of Neoral with other chemical compounds

  • Despite a similar CsA exposure, the control group had a significantly lower MPA AUC0-12h and higher MPAG trough concentration than patients on dual therapy at month 21 post-Tx [12].
  • The Ca2+ dependence of mono-exponential time constants was disrupted by cyclosporin A (CsA), an inhibitor of the Ca(2+)- and calmodulin-dependent phosphatase calcineurin [19].
  • SNP caused loss of the mitochondrial membrane electrical potential, which was prevented by cyclosporin A (CsA), a specific inhibitor of PTP formation [20].
  • The control group (n = 16) received CsA and saline injections twice daily and the treatment group (n = 4) received CsA and angiopeptin (60 micrograms/rabbit daily s.c.) in 2 divided doses [21].
  • Memory CTL abound in steroid resistant grafts and may have a markedly different response to CSA immunotherapy, suggesting a possible mechanism for steroid resistance [22].

Gene context of Neoral

  • Rapa and mainly CsA (but not FK506) and hsp90 ligands promote by their own apoptosis in MCF-7, in MERA, and in HERB cells and in MDA-MB-231 ER-null cells [23].
  • This argues against a previously postulated specific role for Cyp-C in the nephrotoxic effects of CsA in humans, based on the studies of its relative abundance in murine kidney [24].
  • Cyclophilin (CyP) is the 17.8-kDa cytosolic receptor of the immunosuppressant cyclosporin A (CsA) and also a peptidyl prolyl cis-trans isomerase (PPIase) [25].
  • The targets for these drugs, cyclophilin for CsA and FKBP for FK506 and rapamycin, are members of two unrelated families of ubiquitous, highly conserved, abundant proteins [26].
  • The CYPs activities were assessed by measuring the rate of acetanilide 4-hydroxylation (CYP1A2) and cyclosporine A oxidation (CYP3A4) after treatment with TCDD (a CYP1A subfamily inducer) or rifampicin (mainly a CYP3A4 inducer) [27].

Analytical, diagnostic and therapeutic context of Neoral

  • Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group) [28].
  • BACKGROUND: Cyclosporine A (CsA) and tacrolimus (Tac) provide effective immunosuppression after orthotopic liver transplantation (OLT) but can cause renal dysfunction that may progress to end-stage renal failure (ESRF) [29].
  • Because immunosuppressive agents such as CsA induce significant side effects, including bone loss, other therapeutic agents supporting successful vascularized bone allografts have been sought after [30].
  • We previously reported that vascularized bone allograft using immunosuppressants, such as cyclosporine A (CsA), is one approach for reconstruction of large bone defects in both experimental animals (Microsurgery 15:663; 1994) and clinically in humans (Lancet 347:970, 1996) [30].
  • We show that TCR ligation in the presence of FK506 or CsA induced rapid modifications in LAT that modulate the electrophoretic mobility of the molecule in SDS-PAGE [13].


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  2. Linomide, a novel immunomodulator that prevents death in four models of septic shock. Gonzalo, J.A., González-García, A., Kalland, T., Hedlund, G., Martínez, C., Kroemer, G. Eur. J. Immunol. (1993) [Pubmed]
  3. Influence of vitamin D receptor genotype on bone mass changes after renal transplantation. Torres, A., Machado, M., Concepción, M.T., Martín, N., Lorenzo, V., Hernández, D., Rodríguez, A.P., Rodríguez, A., de Bonis, E., González-Posada, J.M., Hernández, A., Salido, E. Kidney Int. (1996) [Pubmed]
  4. Calcineurin Promotes Infection of the Cornea by Candida albicans and Can Be Targeted To Enhance Fluconazole Therapy. Onyewu, C., Afshari, N.A., Heitman, J. Antimicrob. Agents Chemother. (2006) [Pubmed]
  5. Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Maciejewski, J.P., Risitano, A., Sloand, E.M., Nunez, O., Young, N.S. Blood (2002) [Pubmed]
  6. Specific cross-linking of the proline isomerase cyclophilin to a non-proline-containing peptide. McNew, J.A., Sykes, K., Goodman, J.M. Mol. Biol. Cell (1993) [Pubmed]
  7. Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl-X(L). Vieira, H.L., Boya, P., Cohen, I., El Hamel, C., Haouzi, D., Druillenec, S., Belzacq, A.S., Brenner, C., Roques, B., Kroemer, G. Oncogene (2002) [Pubmed]
  8. Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore. Zunino, S.J., Storms, D.H. Cancer Lett. (2006) [Pubmed]
  9. Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of meibomian gland dysfunction. Perry, H.D., Doshi-Carnevale, S., Donnenfeld, E.D., Solomon, R., Biser, S.A., Bloom, A.H. Cornea (2006) [Pubmed]
  10. Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment. Dittrich, K., Knerr, I., Rascher, W., Dötsch, J. Pediatr. Nephrol. (2006) [Pubmed]
  11. Transient immunosuppression with 15-deoxyspergualin prolongs reporter gene expression and reduces humoral immune response after adenoviral gene transfer. Cichon, G., Strauss, M. Gene Ther. (1998) [Pubmed]
  12. Glucocorticoids interfere with mycophenolate mofetil bioavailability in kidney transplantation. Cattaneo, D., Perico, N., Gaspari, F., Gotti, E., Remuzzi, G. Kidney Int. (2002) [Pubmed]
  13. Modulation of the electrophoretic mobility of the linker for activation of T cells (LAT) by the calcineurin inhibitors CsA and FK506: LAT is a potential substrate for PKC and calcineurin signaling pathways. Cho, C.S., Elkahwaji, J., Chang, Z., Scheunemann, T.L., Manthei, E.R., Hamawy, M.M. Cell. Signal. (2003) [Pubmed]
  14. Differential response of glutamine in cultured neurons and astrocytes. Rama Rao, K.V., Jayakumar, A.R., Norenberg, M.D. J. Neurosci. Res. (2005) [Pubmed]
  15. Enhanced renal allograft rejection by inhibitors of nitric oxide synthase: a nonimmunologic influence on alloreactivity. Stojanovic, T., Gröne, H.J., Gieseler, R.K., Klanke, B., Schlemminger, R., Tsikas, D., Gröne, E.F. Lab. Invest. (1996) [Pubmed]
  16. The interaction of immunosuppressive compounds in tandem stimulated peripheral human lymphocytes. Weaver, J.L., Pine, P.S., Aszalos, A. Immunopharmacology and immunotoxicology. (1994) [Pubmed]
  17. NFATc1: a novel anabolic therapeutic target for osteoporosis. Yeo, H., McDonald, J.M., Zayzafoon, M. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  18. Effect of PSC 833 on the cytotoxicity and pharmacodynamics of mitoxantrone in multidrug-resistant K562 cells. Fukushima, T., Yamashita, T., Takemura, H., Suto, H., Kishi, S., Urasaki, Y., Ueda, T. Leuk. Res. (2000) [Pubmed]
  19. Compensatory and excess retrieval: two types of endocytosis following single step depolarizations in bovine adrenal chromaffin cells. Engisch, K.L., Nowycky, M.C. J. Physiol. (Lond.) (1998) [Pubmed]
  20. Participation of the mitochondrial permeability transition pore in nitric oxide-induced plant cell death. Saviani, E.E., Orsi, C.H., Oliveira, J.F., Pinto-Maglio, C.A., Salgado, I. FEBS Lett. (2002) [Pubmed]
  21. Inhibition of coronary artery transplant atherosclerosis in rabbits with angiopeptin, an octapeptide. Foegh, M.L., Khirabadi, B.S., Chambers, E., Amamoo, S., Ramwell, P.W. Atherosclerosis (1989) [Pubmed]
  22. Granulysin expression is a marker for acute rejection and steroid resistance in human renal transplantation. Sarwal, M.M., Jani, A., Chang, S., Huie, P., Wang, Z., Salvatierra, O., Clayberger, C., Sibley, R., Krensky, A.M., Pavlakis, M. Hum. Immunol. (2001) [Pubmed]
  23. Estrogen receptor alpha and beta subtype expression and transactivation capacity are differentially affected by receptor-, hsp90- and immunophilin-ligands in human breast cancer cells. Gougelet, A., Bouclier, C., Marsaud, V., Maillard, S., Mueller, S.O., Korach, K.S., Renoir, J.M. J. Steroid Biochem. Mol. Biol. (2005) [Pubmed]
  24. Human cyclophilin C: primary structure, tissue distribution, and determination of binding specificity for cyclosporins. Schneider, H., Charara, N., Schmitz, R., Wehrli, S., Mikol, V., Zurini, M.G., Quesniaux, V.F., Movva, N.R. Biochemistry (1994) [Pubmed]
  25. Solution conformation of a cyclophilin-bound proline isomerase substrate. Kakalis, L.T., Armitage, I.M. Biochemistry (1994) [Pubmed]
  26. Proline isomerases at the crossroads of protein folding, signal transduction, and immunosuppression. Heitman, J., Movva, N.R., Hall, M.N. New Biol. (1992) [Pubmed]
  27. Perazine as a potent inhibitor of human CYP1A2 but not CYP3A4. Wójcikowski, J., Pichard-Garcia, L., Maurel, P., Daniel, W.A. Polish journal of pharmacology. (2002) [Pubmed]
  28. Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis. Miyamoto, T., Matsumori, A., Hwang, M.W., Nishio, R., Ito, H., Sasayama, S. J. Am. Coll. Cardiol. (2001) [Pubmed]
  29. Mycophenolate mofetil for renal dysfunction after pediatric liver transplantation. Evans, H.M., McKiernan, P.J., Kelly, D.A. Transplantation (2005) [Pubmed]
  30. Effects of vitamin D analog, 22-oxa-1,25-dihydroxyvitamin D(3), on bone reconstruction by vascularized bone allograft. Merida, L., Shigetomi, M., Ihara, K., Tsubone, T., Ikeda, K., Yamaguchi, A., Sugiyama, T., Kawai, S. Bone (2002) [Pubmed]
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