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Chemical Compound Review

FK-565     (2R,6S)-2-amino-6-[[(1R)-1...

Synonyms: KST-1A8479, AC1L3GPT, AC1Q2VSL, FR-41565, AR-1A3081, ...
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Disease relevance of FK-565

  • The heptanoyl tripeptide, FK-565 is a biological response modifier with potent therapeutic properties for the treatment of experimental and spontaneous metastases [1].
  • FK-565 (heptanoyl-gamma-D-Glu-(L-meso-a, epsilon-A2pm (L)-D-AlaOH) is a synthetic acyltripeptide closely resembling cell wall peptidoglycan peptides of Streptomyces in structure [2].
  • Human blood monocytes were isolated by counter-flow centrifugal elutriation from healthy donors and these noncytotoxic monocytes were rendered tumoricidal to allogeneic melanoma (A375) cells by activation with a synthetic acyltripeptide (FK-565), as assessed by measuring release of [125I]iododeoxyuridine in 72 h [3].
  • Alveolar macrophages (AM) lavaged from lungs of F344 rats were activated by in vitro treatment with FK-565 and its derivatives at concentrations of 1-50 micrograms/ml medium, and the activated AM killed syngeneic mammary adenocarcinoma cells [2].
  • FK-565 inhibited splenomegaly in intravenous and oral doses of 0.01 to 1 mg/kg, but time of initial dosing had little effect on this inhibition [4].

Psychiatry related information on FK-565


High impact information on FK-565

  • Furthermore, when the LAK cells induced by culture with IL-2 in the presence or absence of CP/FK-565 were co-cultured with tumour cells, the production of these cytokines was significantly enhanced [6].
  • Treatment of blood mononuclear cells (MNC) of healthy donors with cisplatin or FK-565 in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer (NK)-resistant Daudi cells as assessed by the 4 h 51Cr release assay [7].
  • The macrophage-mediated cytotoxicity was significantly enhanced when TNF-primed macrophages were treated with cisplatin, LPS, FK-565 or interferon-gamma for 24 h, compared to unprimed and treated macrophages [8].
  • FK-565 also acted synergistically with rIFN-gamma to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P [3].
  • The fixed-monocyte-mediated cytotoxicity to A375 cells was induced by the synergistic actions of FK-565 and recombinant interferon-gamma (rIFN-gamma), but not other cytokines [rIFN-alpha A, rIFN-beta, tumor necrosis factor (TNF), interleukin (IL)-2, -3 and -6] [3].

Chemical compound and disease context of FK-565


Biological context of FK-565


Anatomical context of FK-565

  • Tumor cytotoxicity of human monocyte membrane-bound interleukin-1 alpha induced by synergistic actions of interferon-gamma and synthetic acyltripeptide, FK-565 [3].
  • Doses of FK-565 greater than 5 mg/kg are required for in vivo augmentation of natural killer cells, macrophages, and for therapeutic activity, presumably because FK-565 is a peptide small molecular mass which is rapidly degraded and excreted [1].
  • In addition to its therapeutic properties, which were consistently greater than the positive control at optimal doses, FK-565 had significant immunoaugmentary properties for natural killer cells, macrophages, and T cells both in vitro and in vivo, suggesting that its therapeutic activity is due to immune augmentation [1].
  • We have shown that treatment of PBMC with IL-2 for four days caused an increase in intracellular free calcium and in ATP levels, which were further significantly enhanced when LAK cells were generated in the presence of CP/FK-565 [13].
  • In vitro and in vivo evaluation of effects of a heptanoyl tripeptide, FK-565, on porcine macrophage and lymphocyte function [14].

Associations of FK-565 with other chemical compounds


Gene context of FK-565


Analytical, diagnostic and therapeutic context of FK-565


  1. Immunomodulatory and therapeutic properties of FK-565 in mice. Talmadge, J.E., Lenz, B., Schneider, M., Phillips, H., Long, C. Cancer Immunol. Immunother. (1989) [Pubmed]
  2. Activation by a new synthetic acyltripeptide and its analogs entrapped in liposomes of rat alveolar macrophages to the tumor cytotoxic state. Sone, S., Mutsuura, S., Ogawara, M., Utsugi, T., Tsubura, E. Cancer Immunol. Immunother. (1984) [Pubmed]
  3. Tumor cytotoxicity of human monocyte membrane-bound interleukin-1 alpha induced by synergistic actions of interferon-gamma and synthetic acyltripeptide, FK-565. Inamura, N., Sone, S., Okubo, A., Kunishige, E., Nakanishi, M., Ogura, T. Cancer Immunol. Immunother. (1989) [Pubmed]
  4. Inhibitory effect of FK-565 alone and in combination with zidovudine on retroviral infection by Friend leukemia virus in mice. Yokota, Y., Wakai, Y., Watanabe, Y., Mine, Y. J. Antibiot. (1988) [Pubmed]
  5. Immunoactive peptides, FK-156 and FK-565. III. Enhancement of host defense mechanisms against infection. Mine, Y., Watanabe, Y., Tawara, S., Yokota, Y., Nishida, M., Goto, S., Kuwahara, S. J. Antibiot. (1983) [Pubmed]
  6. Increased release of interleukin-1 and tumour necrosis factor by interleukin-2-induced lymphokine-activated killer cells in the presence of cisplatin and FK-565. Basu, S., Sodhi, A. Immunol. Cell Biol. (1992) [Pubmed]
  7. Up-regulation of induction of lymphokine (IL-2)-activated killer (LAK) cell activity by FK-565 and cisplatin. Basu, S., Sodhi, A., Singh, S.M., Suresh, A. Immunol. Lett. (1991) [Pubmed]
  8. Effect of TNF priming of murine peritoneal macrophages on their activation to a tumoricidal state. Singh, R.K., Sodhi, A. Immunol. Lett. (1991) [Pubmed]
  9. Antitumor effects of novel immunoactive peptides, FK-156 and its synthetic derivatives. Izumi, S., Nakahara, K., Gotoh, T., Hashimoto, S., Kino, T., Okuhara, M., Aoki, H., Imanaka, H. J. Antibiot. (1983) [Pubmed]
  10. WS1279, a novel lipopeptide isolated from Streptomyces willmorei. Biological activities. Tanaka, M., Hori, Y., Sakai, F., Ueda, H., Goto, T., Okuhara, M., Tsuda, Y., Okada, Y. J. Antibiot. (1993) [Pubmed]
  11. Pharmacotherapy of dilated cardiomyopathy: current status and future directions. Kawai, C. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. (1992) [Pubmed]
  12. Immunoactive peptides, FK 156 and FK 565. IV. Activation of mouse macrophages. Watanabe, Y., Tawara, S., Mine, Y., Kikuchi, H. J. Antibiot. (1985) [Pubmed]
  13. Up-regulation of IL-2 induced lymphokine activated killer cell activity by cisplatin and FK-565: involvement of calcium ion. Sodhi, A., Basu, S. Immunol. Lett. (1992) [Pubmed]
  14. In vitro and in vivo evaluation of effects of a heptanoyl tripeptide, FK-565, on porcine macrophage and lymphocyte function. Chitko, C.G., Chapes, S.K., Thaler, R.C., Nelssen, J.L., Anderson, G.A., Clough, E.R., Blecha, F. Am. J. Vet. Res. (1991) [Pubmed]
  15. Bleomycin and FK 565 enhance the release of GM-CSF from LPS-stimulated BALB/c peritoneal macrophages. Blaney, B.A., Turk, J.L. Immunopharmacology and immunotoxicology. (1995) [Pubmed]
  16. Activation of tumoricidal properties in macrophages and inhibition of experimentally-induced murine metastases by a new synthetic acyltripeptide, FK-565. Inamura, N., Nakahara, K., Kino, T., Gotoh, T., Kawamura, I., Aoki, H., Imanaka, H., Sone, S. Journal of biological response modifiers. (1985) [Pubmed]
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