KRN7000

Molecular Weight: 842.323 g/mol
Molecular Formula: C₅₀H₉₉NO₈

Source: Analog derived from the sponge Agelas mauritianus. (PORIFERA)
Activity: antitumor, immunostimulatory
Status:Phase I clinical trials (Europe and Asia)

A collaboration between employees of Japan's Kirin Brewery and the University of the Ryukyus published a report describing the first known isolation of a chemical class called the alpha-galactosylceramides from a natural source (the sponge Agelas mauritianus).

These compounds, dubbed the agelasphins, were shown to exhibit antitumor and possible immunostimulatory activity. Further work revealed pronounced in vivo activity against B16 melanoma in mice.

This work prompted the synthesis of a number of derived compounds, including KRN7000

Survival rates of mice inoculated with B16 and EL-4 cancer cells and then treated with the synthetic compound were increased significantly over those that did not receive the drug. Observation that KRN7000 markedly stimulates lymphocytic proliferation under certain conditions indicates the drug may be a powerful biological response modifier. Another animal study revealed KRN7000 significantly inhibited tumor growth and metastasis in the liver.

KRN700 activity is unusual in that it appears to stimulate the production of natural killer T (NKT) cells in the body. These are blood plasma cells with cytotoxic anti-tumor activity that target lipids rather than proteins. Recent efforts, led by the Kirin researchers, have uncovered similar NKT cell activators in mammals.

KRN7000 was placed into Phase I trials for cancer immunotherapy in Asia and Europe in 2001.

NCBI PubChem compound summary page - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Giaccone G, Punt C, Ando Y, Ruijter R, Nishi N, Peters M, von Blomberg BME, Scheper R, Roelvink M, Beijnen J, Zwierzina H, and H Pinedo. 2000. KRN7000, an NKT Cell Enhancer, in Patients with Solid Tumors - A Phase I Study of the EORTC BTDG. American Society of Clinical Oncology Annual Meeting.

Kobayashi E, Motoki K, Uchida T, Fukushim H, and Y Koezuka. 1995. KRN7000, a novel immunomodulator, and its antitumor activities. Oncol Res. 7:529-34.

Nakagawa R, Serizawa I, Motoki K, Sato M, Ueno H, Iijima R, Nakamura H, Shimosaka A, and Y Koezuka. 2000. Antitumor activity of alpha-galactosylceramide, KRN7000, in mice with the melanoma B16 hepatic metastasis and immunohistological study of tumor infiltrating cells. Oncol. Res. 12:51-8.

Newman DJ, and GM Cragg. 2004. Advanced Preclinical and Clinical trials of natural Products and Related Compounds from marine Sources. Current Medicinal Chemistry 11:1693-1713.