RE: TO ALL KNOWLEDGABLE READERSThis is the TLN annual information return 2008 - also available on SEDAR:
https://rapidshare.com/files/238982007/AnnualInfoReturn.pdf.html
On page 15...
TLN-4601 was evaluated on different types of human tumor cell lines for its ability to interfere with Ras
processing via protein prenylation by monitoring farnesyl transferase (FTase) and Geranylgeranyl
transferase (GGTase) I activities. Downstream Ras signaling events, such as Raf-1 and ERK1/2
phosphorylation, were also evaluated by immunoblots.
No mobility shift of either HDJ2 or Rap1A
(surrogate markers of FTase and GGTase I, respectively) were observed in cells exposed to TLN-4601 for
up to 48h suggesting TLN-4601 does not inhibit Ras prenylation. In contrast, a strong inhibition of EGFinduced
phosphorylation of c-Raf-1 and ERK1/2 in mutated cancer cell lines tested was shown. This
effect was time-dependent with complete inhibition of protein phosphorylation within 6h. Recent
data
indicate that TLN-4601 decreases Ras-GTP levels (active form of Ras) and total Raf-1 protein levels
leading to an inhibiton of MEK and ERK phosphorylation. Other studies showed that TLN-4601 does not
directly inhibit EGFR, c-Raf, MEK1, ERK1 or ERK2 kinase activities. Taken together, TLN-4601 is not
a FTase inhibitor and inhibits Ras signaling by inhibiting Ras activation and decreasing Raf-1 protein.
Further experiments are ongoing to establish the specific target(s)/mechanism by which these effects are
mediated.
Thescience is clear. 4601 does not act like Concordia,s product. There isno one hidding anything. 4601 is a superior product because it blocksall downstream even. This means that PI3K is block, ERK/MEK etc.
Thisis year 1, of drug combo. ASCO 2009 is about personalized medicine. Anew shift in oncology, before people were focussing on finding the"blockbuter" drug. A stand alone product. Now combo is the new standardof care.