HEMIASTERLINS

Molecular Weight (Hemiasterlin): 526.711 g/mol
Molecular Formula (Hemiasterlin): C₃₀H₄₆N₄O₄

Source: Sponges of genus Auletta, Siphonochalin (PORIFERA)
Activity: cytotoxic and tubulin interactive agents
Status:Preclinical

This class of novel marine oligopeptides have been shown to be potent antitumor agents. Representatives of this class of natural products have been isolated from extracts prepared from sponges residing in two distinct genera (Auletta; Siphonochalina). Three different hemiasterlins with drug development potential (hemiasterlin, hemiasterlin A, hemiasterlin C) have been the subject of chemical and biological investigations.

These molecules exhibit cytotoxic and antitubulin activity similar to that seen in the dolastatins. Mitotic inhibition occurs through binding to tubulin at the vinca/peptide region in a manner similar to dolastatin.

The production of synthetic hemiasterlin analogs, facilitated by the simple tripeptide molecular structure, has been achieved. Studies have demonstrated that one analog, HTI-286, effectively inhibits tubulin polymerization, disrupts cell microtubule organization, and induces mitotic arrest and apoptosis.

NCBI PubChem compound summary page - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Gamble, W.R., Durso, N.A., Fuller, R.W., Westergaard, C.K., Johnson, T.R., Sackett, D.L., Hamel, E., Cardellina, J.H. 2nd, Boyd, M.R.. 1999. Cytotoxic and tubulin-interactive hemiasterlins from Auletta sp. and Siphonochalina spp. sponges. Bioorg. Med. Chem. 7:1611-1615.

Frank Loganzo, Carolyn M. Discafani, Tami Annable, Carl Beyer, Sylvia Musto, Malathi Hari, Xingzhi Tan, Carolyn Hardy, Richard Hernandez, Michelle Baxter, Thiruvikraman Singanallore, Gulnaz Khafizova, Marianne S. Poruchynsky, Tito Fojo, James A. Nieman, Semiramis Ayral-Kaloustian, Arie Zask, Raymond J. Andersen, and Lee M. Greenberger. 2003. HTI-286, a Synthetic Analogue of the Tripeptide Hemiasterlin, Is a Potent Antimicrotubule Agent that Circumvents P-Glycoprotein-mediated Resistance in vitro and in vivo. Cancer Research 63:1838-1845.