Anyone come across TZT 1027? Anyone heard of UK/Europe trials?

Thanks

Ian

Tzt-1027:
A substance that is being studied as a treatment for cancer. It belongs to
the family of drugs called tubulin inhibitors. Also called soblidotin.
http://www.health-dictionary.com/cancer_term_details/Tzt-1027


TZT-1027, a novel dolastatin 10 derivative: Phase I and pharmacologic study
of day 1 and 8 IV administration every 3 weeks in patients (pts) with
advanced solid tumors
TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces
tumor cell death.
Otani M, Natsume T, Watanabe JI, Kobayashi M, Murakoshi M, Mikami T,
Nakayama T.
Safety Research Department, Teikoku Hormone Mfg. Co., Ltd., Takatsu-ku,
Kawasaki-shi, Kanagawa 213-8522, Japan. otani-m@....
TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with
potent antitumor activity both in vitro and in vivo. In this study, we
performed biochemical and histopathological examinations, and evaluated
TZT-1027-induced tumoral vascular collapse and tumor cell death in an
advanced tumor model, murine colon 26 adenocarcinoma. In addition, we
studied the effects of TZT-1027 on cultured human umbilical vein endothelial
cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective
hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral
area of the tumor mass. Measurements of tumoral hemoglobin content and dye
permeation revealed that the hemorrhage occurred firstly and tumor blood
flow stopped secondarily. The vascular damage was followed by continuous
induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor
regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with
membrane blebbing in 30 min. These cell changes were completely inhibited by
K252a, a broad-spectrum inhibitor of protein kinases. These effects of
TZT-1027 on both tumor vasculature and HUVEC were greater than those of
vincristine. In conclusion, TZT-1027 quickly attacked the well-developed
vascular system of advanced tumors by a putative protein kinase-dependent
mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a
conventional antitumor activity and a unique anti-tumoral vascular activity,
making it a potentially powerful tool for clinical cancer therapy.
PMID: 10965026 [PubMed - indexed for MEDLINE
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=Pu
bMed&list_uids=10965026&dopt=Abstract