CRYPTOPHYCINS

Molecular Weight (Cryptophycin 1): 655.177 g/mol
Molecular Formula (Cryptophycin 1): C₃₅H₄₃ClN₂O₈

Source: marine and non-marine cyanophytes; Dysidea arenaria (PORIFERA)
Activity: tubulin interactive agent, antifungal, cytotoxin
Status: Clinical trials of semi-synthetic cryptophycin 52 discontinued in 2002.

This family of compounds was initially reported from a terrestrial source (the Nostoc sp. cyanophyte component of a Scottish lichen). Representative compounds have also been found in species of free-living marine and non-marine cyanophytes and, more recently, from the Japanese sponge Dysidea arenaria.

The expressed bioactivity that was originally pursued was activity as an antifungal agent. Development of the compound for this purpose was not pursued beyond preliminary investigations when it was deemed too toxic for human use.

More recently it has been reported that cryptophycin 1 is an inhibitor of tubulin assembly in cells, likely binding to tubulin at the so-called "peptide binding site" in a manner similar to that suspected for dolastatin 10 and the hemiasterlin derivative HTI-286.

Lilly licensed the compounds from the University of Hawaii and Wayne State University, and utilized a semi-synthetic approach to build the modified natural product cryptophycin 52. This compound progressed through Phase I and toward Phase II human clinical trials before trials were discontinued in 2002.

Cryptophycin 24 (arenastatin A) from the Okinawan sponge Dysidea arenari is reported to be a potent cytotoxin.

NCBI PubChem compound summary page - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

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.