Akio Kuroda

Bio: Akio Kuroda is an academic researcher. The author has contributed to research in topics: Alkyl & Alkoxy group. The author has an hindex of 10, co-authored 16 publications receiving 808 citations.

FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. II. Fermentation, isolation and physico-chemical and biological characteristics.

Abstract: FR-900520 and FR-900523, novel neutral macrolide immunosuppressants, were isolated from the cultured broth of Streptomyces hygroscopicus subsp. yakushimaensis No. 7238. Their molecular formulae were determined as C43H69NO12 and C42H67NO12, respectively. The compounds suppressed immune response in vitro. IC50 values of FR-900520 and FR900523 for mouse mixed lymphocyte reaction were 0.55 nM and 1.6nM, respectively. FR900520, the major component, clealy prolonged skin allograft survival in rats.

Condensed imidazole derivatives and processes for preparation thereof

Abstract: There are described compounds of the formula: wherein R1 is lower alkyl, halo(lower)alkyl, cyclo(lower)alkyl or lower alkylthio, R2 is hydrogen or imino-protective group, R3 is hydrogen or halogen, A is lower alkylene, and is a group of the formula : , or in which X1, X2, X3 and X4 are each N or CR4, in which R4 is hydrogen, lower alkyl, lower alkoxy, halogen, halo(lower)alkyl, esterified carboxy, halo(lower)alkoxy or hydroxy, provided that at least one of X1, X2, X3 and X4 is N, and pharmaceutically acceptable salts thereof. These compounds are useful as potent and selective antagonists of angiotensin II receptor and can be used as therapeutical and/or preventive agents for cardiopathy (e.g. angina pectoris, arrhythmia, miocardial infarction, etc.) hyperaldosteronism cerebral vascular diseases, senile dementia, ophthalmic diseases (e.g.) glaucoma, etc.), and the like, as well as diagnostic agents for testing the renin angiotensin system. The preparation of these compounds , pharmaceutical compositions containing them, the medical treatment or prevention of angiotensin IImediated diseases, hypertension or heart failure using these compounds are also disclosed.

Imidazole derivatives, potent and selective antagonists of angiotensin II receptor

Abstract: A compound of the formula : wherein R1 is hydrogen, halogen, nitro, lower alkyl, lower alkoxy, amino or acylamino, R2, R3 and R4 are each hydrogen, halogen, nitro, cyano, lower alkyl, lower alkenyl, lower alkylthio, more or di or trihalo(lower)alkyl, oxo(lower)alkyl, hydroxy(lower)alkyl or optionally esterified carboxy; or R2 and R3 are linked together to form 1,3-butadienylene, R5 is hydrogen or imino-protective group, A is lower alkylene, Q is CH or N, X is N or CH, Y is NH, O or S, and is condensed or uncondensed imidazolyl which may have suitable substituent(s), and pharmaceutically acceptable salt thereof; processes for their preparation and pharmaceutical compositions comprising them.

FR65814, a novel immunosuppressant isolated from a Penicillium strain. Taxonomy, fermentation, isolation, physico-chemical and biological characteristics and structure assignment.

Abstract: FR65814, a novel immunosuppressant, was isolated from the cultured broth of Penicillium jensenii F-2883. The structure was assigned to be 5, 6-dihydroxy-4-(l, 2-epoxy-1, 5-dimethyl-4-hexenyl)-1-oxaspiro[2, 5]octane by spectroscopic analyses. The compound suppressed the immune response at low concentration. In addition, a structually related component fumagillol, a known carcinolytic agent, was also isolated and found to show immunosuppressive activity.

Drug Discovery: A Historical Perspective

Abstract: Driven by chemistry but increasingly guided by pharmacology and the clinical sciences, drug research has contributed more to the progress of medicine during the past century than any other scientific factor. The advent of molecular biology and, in particular, of genomic sciences is having a deep impact on drug discovery. Recombinant proteins and monoclonal antibodies have greatly enriched our therapeutic armamentarium. Genome sciences, combined with bioinformatic tools, allow us to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future medicines, thereby increasing the number of treatment options. The dramatic increase in the complexity of drug research is enforcing changes in the institutional basis of this interdisciplinary endeavor. The biotech industry is establishing itself as the discovery arm of the pharmaceutical industry. In bridging the gap between academia and large pharmaceutical companies, the biotech firms have been effective instruments of technology transfer.

Immunosuppressive Drugs for Kidney Transplantation

Abstract: Suppression of allograft rejection is central to successful organ transplantation; thus, immunosuppressive agents are crucial for successful allograft function. Immunosuppressive drugs are used for induction (intense immunosuppression in the initial days after transplantation), maintenance, and reversal of established rejection. This review considers the use of immunosuppressive drugs in organ transplantation, focusing on renal transplantation.

A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase.

Abstract: THE structurally novel macrolide FK506 (refs 1,2) has recently been demonstrated to have potent immunosuppressive activity3–7 at concentrations several hundredfold lower than cyclosporin A (CsA). Cyclosporin A, a cyclic peptide, has found widespread clinical use in the prevention of graft rejection following bone marrow and organ transplantation8. The mechanisms of immunosuppression mediated by FK506 and CsA appear to be remarkably similar, suggesting that these unrelated structures act on a common receptor or on similar molecular targets, perhaps the CsA receptor, cyclophilin9–11, which has recently been shown by Fischer etal.12 and Takahashi etal.13 to have cis–trans peptidyl-prolyl isomerase activity. We have prepared an FK506 affinity matrix and purified a binding protein for FK506 from bovine thymus and from human spleen. This FK506-binding protein (FKBP) has a relative molecular mass (Mr) of ∼14,000(14K), a pi of 8.8–8.9, and does not cross-react with antisera against cyclophilin. The first 40 N-terminal residues of the bovine and 16 residues of the human FKBP were determined; the 16-residue fragments are identical to each other and unrelated to any known sequences. This protein catalyses the cis–trans isomerization of the proline amide in a tetrapeptide substrate and FK506 inhibits the action of this new isomerase. The FKBP and cyclophilin appear to be members of an emerging class of novel proteins that regulate T cell activation and other metabolic processes, perhaps by the recognition (and possibly the isomerization) of proline-containing epitopes in target proteins.

FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.

Abstract: The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1nM and 10nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.

FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics.

Abstract: FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukubaenis No. 9993 as colorless prism and the molecular formula was determined as C44H69NO12.H2O. The compound suppressed immune responses in vitro and in vivo with mice. This immunosuppressive effect was more potent than that of ciclosporin.