A230
Human Cancer Xenograft Studies of Angiogenesis Inhibitor YN968D1 as an Anti-Tumor Agent.
Luisa Iruela-Arispe,1 Liguang Lou,2 Xiuhua Chen,2 Paul
Chen.2 University of California, Los Angeles,1 Los Angeles, CA, Advenchen Laboratories, LLC,2 Thousand Oaks, CA.
Note about YN968D1:
cannot find out much about Advenchen Laboratories
or YN968D1 from google but Advenchen Laboratories
did sponsor this:
grc.uri.edu
Note about PTK787:
Oral Angiogenesis Inhibitor in Phase III Trials
for Treatment of Patients with Metastatic Colorectal Cancer
The small molecule PTK787/ZK 222584 entered two Phase III clinical trials for the treatment of metastatic colorectal cancer in early 2003.
schering.de
Angiogenesis inhibitors for the inhibition of VEGFr become a target of considerable interest to pursue for the treatment of cancer.
A new small molecule angiogenesis inhibitor
YN968D1 has been discovered that has in vitro VEGF induced HUVEC assay IC50 30 nM potency and shows better efficacy in several human cancer xenograft studies comparing in the parallel with PTK787 that is in Phase III clinical trial.
YN968D1 produces remarkable preclinical antitumor activity on human colon cancer LS174t, HT29, LOVO and human A431 xenograft models.
It generates dose response as well and it has similar activity to 5-FU. All animals treated orally have no significant body weight change and have tumor size difference visually between treatment and control groups after tumor extraction. These experiments conducted in two to three weeks dosing at mostly 70 mg/kg and tumors were implanted in nude mice 7-10 days reaching volume between 60 to 200 mm3 before oral dosing daily or i.p. dosing once four days.
The results are:
(1) T/C% of YN968D1, PTK787, 5-FU on LS174t are 74%, 107%, 65%;
(2) T/C% of YN968D1, PTK787, oxaliplatin on HT29 are 64%, 73%, 66%;
(3) T/C% of YN968D1 on LOVO are 67%, 74%, 58%, 57%, 38% at 1.2 mg/kg, 3.5 mg/kg, 10mg/kg, 35 mg/kg, 70 mg/kg dose respectively; T/C% of PTK787 on LOVO are 69%
at 70 mg/kg dose.
(4) T/C% of YN968D1, PTK787 on A431 are 22%, 46%.
These results demonstrate the definitive superior in vivo efficacy of YN968D1 over PTK787 and further preclinical studies are on going. |
