Hypothemycin exhibits antifungal and cytotoxic activity against some tumor cell lines partly attributed to inhibition of Ras-inducible genes. Hypothemycin facilitates the ubiquitinylation process of cyclin D1. Hypothemycin has been identified as a potent and selective inhibitor of threonine/tyrosine-specific kinase, MEK, and other protein kinases that contain a conserved cysteine residue in the ATP-binding site in in vitro studies.
1. Sonoda, H., et al., 1999. Suppression of oncogenic transformation by hypothemycin associated with accelerated cyclin D1 degradation through ubiquitin-proteasome pathway. Life sciences. 65(4): 381-94. PMID: 10421424
2. Tanaka, H., et al., 1999. Antitumor efficacy of hypothemycin, a new Ras-signaling inhibitor. Japanese journal of cancer research : Gann. 90(10): 1139-45. PMID: 10595743
3. Camacho, R., et al., 1999. Hypothemycin inhibits the proliferative response and modulates the production of cytokines during T cell activation. Immunopharmacology. 44(3): 255-65. PMID: 10598882
4. Zhao, A., et al., 1999. Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK. The Journal of antibiotics. 52(12): 1086-94. PMID: 10695671
5. Schirmer, Andreas., et al., 2006. Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides. Proceedings of the National Academy of Sciences of the United States of America. 103(11): 4234-9. PMID: 16537514
6. Winssinger, Nicolas., et al., 2007. Chemistry and biology of resorcylic acid lactones. Chemical communications (Cambridge, England). (1): 22-36. PMID: 17279252