KRN7000 Background

α-Galactosylceramide (α-GalCer) or the common name of KRN7000 is an agelasphin derivative developed by Kirin Brewery Co., Ltd., is a biological response modifier (BRM). Agelasphins was isolated from an extract of the Okinawan marine sponge Agelas mauritianus. The Alpha-GalCer structure consist of a galactose combined with a ceramide in an alpha-configuration.

KRN7000 is no longer extracted from the native source, but chemically synthesized. Alpha-GalCer is a specific ligand for human and mouse natural killer T (NKT) cells and KRN7000 exhibits potent anti-tumor activity with murine in vivo experiments including subcutaneous implanted model and metastatic models in the liver and lung. In the liver metastatic models, treatment with KRN7000 suppressed the growth of tumors and prolonged the survival term of the tumor-bearing mice. KRN7000 has been reported to show various immunological effects in infectious diseases, autoimmune disease and graft verse host disease in mice.

Chemical name:
(2S,3S,4R)-1-O-(alpha-D-galactosyl)-N-hexacosanoyl-2-amino-1,3,4-octadecanetriol

KRN7000 chemical properties:
M.W.: 858.34
Molecular Formula: C50H99NO9
Melting point: 189-190°C
Appearance: Off-white powder
Solubility: Insoluble in water, methanol, ethanol or
other organic solvents, very slightly soluble in
tetrahydrofuran, slightly soluble in pyridine

 

KRN7000 chemical structure:

Alpha-GalCer chemical structure


KRN7000 (Alpha-GalCer) Adobe pdf datasheet

Alpha-GalCer (KRN7000) datasheet by Funakoshi Company

Click here to learn how to draw Alpha-GalCer molecule. This weblink is a short animation about the chemical synthesis of Alpha-GalCer.

References:

1) Natori, T., et al. Agelasphins, Novel Antitumor and Immunostimulatory Cerebrosides from the Marine Sponge Agelasmauritianus, Tetrahedron Lett., 34, 5591-5592, (1993).

2) Akimoto, K., et al. Synthesis and Stereochemistry of Agelasphin-9b, Tetrahedron Lett., 34, 5593-5596, (1993).

3) Natori, T., et al. Agelasphins, novel antitumor and immunostimulatory cerebrosides from the marine sponge Agelas mauritianus Tetrahedron, 50, 2771-2784, (1994).

4) Motoki, K., et al. Immunostimulatory and Antitumor Activities of Monoglycosylceramides Having Various Sugar Moieties Biol. Pharm. Bull., 18, 1487-1491, (1995).

5) Morita, M., et al. Syntheses of α-, β-monoglycosylceramides and four diastereomers of an α-galactosylceramide Bioorganic Med. Chem. Lett., 5, Pages 699-704.

6) Motoki, K., et al. Antitumor activities of α-, β-monogalactosylceramides and four diastereomers of an α-galactosylceramide Bioorganic Med. Chem. Lett., 5, 705-710, (1995).

7) Kawano, T., et al. CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science, 278, 1626-1629, (1997).

8) Kronenberg. M. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol., 23 :877-900 (2005).

9) Yamaguchi, Y., et al. Enhancing effects of (2S,3S,4R)- 1-O- (alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino) -1,3,4-octadecanetriol (KRN7000) on antigen-presenting function of antigen-presenting cells and antimetastatic activity of KRN7000-pretreated antigen-presenting cells. Oncology Res., 8, 399-407, (1996).

10) Giaccone, et al. A Phase I Study of the Natural Killer T-Cell Ligand α-Galactosylceramide (KRN7000) in Patients with Solid Tumors Clinical Cancer Res. 8:3702–3709, (2002).

11) Shimizu, K., et al. Cross-presentation of glycolipid from tumor cells loaded with alpha-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells.S, J Exp Med., 204 : 2641-2653 (2007).

12) Ishii Y., et al. Alpha-galactosylceramide-driven immunotherapy for allergy. Front Biosci. 2008 May 1;13:6214-28.

13) Shimizu K., et al. Cross-presentation of glycolipid from tumor cells loaded with alpha-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells J Exp Med. 2007 Oct 29;204(11):2641-53.

14) Kamijuku H. et al. Mechanism of NKT cell activation by intranasal coadministration of alpha-galactosylceramide, which can induce cross-protection against influenza viruses, Mucosal Immunol. 2008 May;1(3):208-218.

Back to top

 

New 7DW8-5 glycolipid

7DW8-5

Now available 7DW8-5 glycolipid derivative of Alpha-GalCer for human and mice iNKT immunoresearch

 

Meet Funakoshi Company
at the following meetings:

The 11th Annual Meeting of Japanese Society for Epigentics
Tokyo, Japan
May 22-23, 2017

The 36th Annual Meeting of Japanese Association of Forensic Toxicology

The 21st Annual Meeting of Japanese Assocation of Cancer Immunology
Chiba, Japan
June 28-30, 2017

The Japanese Society for Genome Editing
Osaka, Japan
June 28-30, 2017

The 76th Annual Meeting of the Japanese Cancer Association
Yokohama, Japan
September 28-30, 2017

NIH Festival
Bethesda, Maryland
September 2017

ASCB
Philadelphia, PA
December 2-6, 2017