Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Indications -- Cancer -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (313)	11/20/2002 11:40:17 PM
From: Miljenko Zuanic	Respond to of 1840

I think it is relative to SU5416? Indolinone derivative. It appears that does have broad activity toward RTK. Abstract 194: Mechanism of action and biomarker studies of SU11248, a selective inhibitor of split kinase domain receptor tyrosine kinases (including VEGF receptors, PDGF receptors, c-Kit, and Flt3) Citation: European Journal of Cancer Vol 38, Suppl. 7, November 2002, page 61 O. Potapova, A. Laird, M. Nannini, G. Li, K. Moss, J. Cherrington, D. Mendel SUGEN, Inc., Preclinical Research and Translational Medicine, South San Francisco, USA Several members of the split kinase domain (Class III) superfamily of receptor tyrosine kinases (RTKs) are implicated in cancer. These include the VEGF receptors VEGFR2/KDR and VEGFR1/Flt-1, the platelet-derived growth factor receptors PDGFRa and PDGFRb, c-Kit, and Flt3. SU11248 is an orally available selective small molecule inhibitor of these RTKs. In biochemical and/or cellular assays, SU11248 inhibited VEGFR2, VEGFR1, the PDGFRs, c-Kit and Flt3 with low nM potency. In human tumor xenografts grown in mice, SU11248 selectively inhibited the phosphorylation of VEGFR2, PDGFRb, c-Kit and an activated mutant form of Flt3 (Flt3-ITD), but did not inhibit EGFR phosphorylation. SU11248 also inhibited biological readouts dependent on the kinase activity of VEGFR2 (vascular permeability) and c-Kit (hair pigmentation) in mice. SU11248 exhibited broad and potent anti-tumor activity in mice, regressing several tumors (including A431 human epidermoid, Colo205 human colon and HT-29 human colon xenografts) and suppressing or delaying the growth of diverse other tumors. Studies were initiated to explore early and late responses to SU11248 treatment in mice bearing tumor xenografts to identify candidate biomarkers of response. Preclinical data will be presented on several candidate tumor biomarkers identified using histological and biochemical approaches and evaluated further preclinically and in the clinic. These include Ki-67 and active Caspase 3, which reflect levels of proliferation and apoptosis, respectively, and phosphoepitopes on several downstream effectors of RTK function. We also report the results of studies using selective inhibitors or VEGF or PDGF receptors, either alone or in combination, to explore the relative contributions of inhibition of these receptor families to the anti-tumor activity of SU11248. SU11248 is currently in Phase I clinical trials in patients with advanced cancer.