Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Pure and Applied Chemistry

The Scientific Journal of IUPAC

Ed. by Burrows, Hugh / Stohner, Jürgen

IMPACT FACTOR 2017: 5.294

CiteScore 2017: 3.42

SCImago Journal Rank (SJR) 2017: 1.212
Source Normalized Impact per Paper (SNIP) 2017: 1.546

See all formats and pricing
More options …
Volume 79, Issue 4


Discovery of micafungin (FK463): A novel antifungal drug derived from a natural product lead

Akihiko Fujie
  • Corresponding author
  • Fermentation Research Laboratories, Astellas Pharma Inc., 5-2-6 Tokodai, Tsukuba, Ibaraki 300-2698, Japan
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-01-01 | DOI: https://doi.org/10.1351/pac200779040603

FR901379, which is a novel, water-soluble, echinocandin-like lipopeptide, was isolated from a microbial culture broth. It showed potent in vivo antifungal activity against Candida albicans and inhibits the synthesis of 1,3-β-glucan. However, this compound had hemolytic activity and was also less active against Aspergillus fumigatus. To overcome these shortcomings, we synthesized FR131535 bearing an octyloxybenzoyl acyl side chain instead of a fatty acid. FR131535 retained the original activity displayed by FR901379, acquired potent anti-Aspergillus activity, and its hemolytic activity was significantly reduced. Further extensive chemical modification of FR901379 has led to the discovery of micafungin (FK463), which is effective against Candida and Aspergillus spp. Micafungin has been marketed in Japan and the United States as a candin-class parenteral antifungal agent for life-threatening mycoses.

Keywords: antifungal drugs; echinocandin; FK463; FR901379; micafungin


International Symposium on Chemistry of Natural Products (ISCNP-25) and 5th International Conference on Biodiversity (ICOB-5), International Conference on Biodiversity, International Symposium on the Chemistry of Natural Products, ICOB, ISCNP, Biodiversity, Natural Products, 25th, Kyoto, Japan, 2006-07-23–2006-07-28


  • 1.

    T. Iwamoto, A. Fujie, K. Sakamoto, Y. Tsurumi, N. Shigematsu, M. Yamashita, S. Hashimoto, M.Okuhara, M. Kohsaka. J. Antibiot. 47, 1084 (1994).CrossrefGoogle Scholar

  • 2.

    T. Iwamoto, A. Fujie, K. Nitta, S. Hashimoto, M. Okuhara, M. Kohsaka. J. Antibiot. 47, 1092 (1994).Google Scholar

  • 3.

    E. Cabib, T. Drgon, J. Drgonova, R. A. Ford, R. Kollar. Biochem. Soc. Trans. 25, 200 (1997).CrossrefGoogle Scholar

  • 4.

    , M. Debono, R. S. Gordee. Annu. Rev. Microbiol. 48, 471 (1994).CrossrefGoogle Scholar

  • 5.

    , A. Fujie, T. Iwamoto, B. Sato, H. Muramatsu, C. Kasahara, T. Furuta, Y. Hori, M. Hino, S.Hashimoto. Bioorg. Med. Chem. Lett. 11, 399 (2001).CrossrefGoogle Scholar

  • 6.

    M. Tomishima, H. Ohki, A. Yamada, H. Takasugi, K. Maki, S. Tawara, H. Tanaka. J. Antibiot. 52, 674 (1999).CrossrefGoogle Scholar

  • 7.

    S. Tawara, F. Ikeda, K. Maki, Y. Morishita, K. Otomo, N. Teratani, T. Goto, M. Tomishima, H.Ohki, A. Yamada, K. Kawabata, H. Takasugi, K. Sakane, H. Tanaka, F. Matsumoto, S.Kuwahara. Antimicrob. Agents Chemother. 44, 57 (2000).Google Scholar

  • 8.

    , F. Ikeda, Y. Wakai, S. Matsumoto, K. Maki, F. Matsumoto, S. Kuwahara. Antimicrob. Agents Chemother. 44, 614 (2000).CrossrefGoogle Scholar

  • 9.

    H. Yamaguchi, T. Hiratani, K. Iwata, Y. Yamamoto. J. Antibiot. 35, 210 (1982).CrossrefGoogle Scholar

  • 10.

    M. Debono, B. J. Abbott, D. S. Fukuda, M. Barnhart, K. E. Willard, R. M. Molloy, K. H. Michel, J. R. Turner, T. F. Butler, A. H. Hunt. J. Antibiot. 42, 389 (1989).CrossrefGoogle Scholar

  • 11.

    D. M. Schmatz, G. Abruzzo, M. A. Powles, D. C. McFadden, J. M. Balkovec, R. M. Black, K.Nollstadt, K. Bartizal. J. Antibiot. 45, 1886 (1992).Google Scholar

  • 12.

    L. D. Boeck, D. S. Fukuda, B. J. Abbott, M. Debono. J. Antibiot. 42, 382 (1989).CrossrefGoogle Scholar

  • 13.

    S. Ueda, M. Tanaka, M. Ezaki, K. Sakamoto, S. Hashimoto, K. Ito, K. Nagao, T. Higaki, N.Oohata, M. Tsuboi, M. Yamashita. Program and Abstracts of the 38th Intersci. Conf. on Antimicrob. Agents Chemother., F-145, p. 269 (1998).Google Scholar

About the article

Published Online: 2009-01-01

Published in Print: 2007-01-01

Citation Information: Pure and Applied Chemistry, Volume 79, Issue 4, Pages 603–614, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1351/pac200779040603.

Export Citation

© 2013 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Qun Yue, Li Chen, Xiaoling Zhang, Kuan Li, Jingzu Sun, Xingzhong Liu, Zhiqiang An, and Gerald F. Bills
Eukaryotic Cell, 2015, Volume 14, Number 7, Page 698
Xiaohan Wang, Minyi Lin, Dan Xu, Daowan Lai, and Ligang Zhou
Molecules, 2017, Volume 22, Number 12, Page 2069
Christina Görgen and Thomas J. J. Müller
Chemistry of Heterocyclic Compounds, 2017, Volume 53, Number 4, Page 422
Marina Rautenbach, Anscha M. Troskie, and J. Arnold Vosloo
Biochimie, 2016, Volume 130, Page 132
Kristin Shirey, Kayla R. Stover, John Cleary, Ngoc Hoang, and Jonathan Hosler
Biochemistry, 2016, Volume 55, Number 14, Page 2100
Armin Bauer and Mark Brönstrup
Nat. Prod. Rep., 2014, Volume 31, Number 1, Page 35
Tamás Emri, László Majoros, Viktória Tóth, and István Pócsi
Applied Microbiology and Biotechnology, 2013, Volume 97, Number 8, Page 3267
Masato Yamada, Kazunobu Yawata, Yohsuke Orino, Satoshi Ueda, Yasuhiro Isogai, Goro Taguchi, Makoto Shimosaka, and Seiji Hashimoto
Current Genetics, 2009, Volume 55, Number 6, Page 623
Seiji Hashimoto
The Journal of Antibiotics, 2009, Volume 62, Number 1, Page 27

Comments (0)

Please log in or register to comment.
Log in