Spongistatins as tubulin targeting agents.
Recently identified novel agents that disrupt tubulin polymerization include synthetic spiroketal pyrans (SPIKET) targeting the spongistatin binding site of b-tubulin. These agents exhibit anticancer activity by disrupting normal mitotic spindle assembly and cell division as well as inducing apoptosis. At nanomolar concentrations, the SPIKET compound SPIKET-P caused tubulin depolymerization in cell-free turbidity assays and exhibited potent cytotoxic activity against cancer cells as evidenced by destruction of microtubule organization, and prevention of mitotic spindle formation in human breast cancer cells. SPIKET compounds represent a new class of tubulin targeting agents that show promise as anti-cancer drugs.
Uckun
F M
FM
Drug Discovery Program and Parker Hughes Cancer Center, Parker Hughes Institute, St. Paul, MN 55113, USA.
Mao
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C
Jan
S T
ST
Huang
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H
Vassilev
A O
AO
Navara
C S
CS
Narla
R K
RK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D011714:Pyrans / Q000378:metabolism / Q000494:pharmacology*; D013141:Spiro Compounds / Q000378:metabolism / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D011714:Pyrans; C409002:SPIKET-P; D013141:Spiro Compounds; D014404:Tubulin