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Biotech / Medical : Tularik Inc. (TLRK) -- Ignore unavailable to you. Want to Upgrade?

To: quidditch who wrote (157)	4/16/2002 12:20:42 PM
From: scaram(o)uche	Respond to of 598

>> I guess the worry is that TLRK had nothing of significance to be leaked (bummer). << I guess I just don't have the right kind of an "of significance" attitude. I think "taxol". I was expecting a "phase II-like" indication that efficacy can be observed at a dose that can be tolerated. Because the company is so vocal about the imminent transition to phase III and because this sounds good to me....... Roxanne Bales has served as our Vice President, Regulatory Affairs since January 2001. Ms. Bales joined Tularik from SangStat, where she had been VP of Regulatory Affairs. Prior to her work at SangStat, Ms. Bales was at Genentech, Inc. for 10 years where she most recently served as Senior Director, Regulatory. Ms. Bales received her BA and MA in Chemistry from the University of California, Irvine. In addition to her work at SangStat and Genentech, she has held positions in health-related fields such as cancer research, pharmaceutical and device development, and toxicology research. ..... , I think that it's a good bet. But, I don't live and breathe this company, and it is a bet, a gamble, or whatever one would label a highly speculative investment. I won't/haven't bet the farm. >> Maybe that's why the EVP for R&D left for other (greener?) pastures in early February. << That was one of biotech's prime slots. The nature of the transition seemed strained, so I haven't got an angle. The company could certainly do a better job of making the investor feel warm and fuzzy. But Tularik isn't lacking for good brains. The programs are leveraged; four of them are hitting on novel targets. Gleevec fever could hit strong, and Tularik is a premium intracellular signaling company. Add that (1) they've retained full rights to most of their programs, and (2) they're pushing at very large markets (obesity, inflammatory diseases, others).

To: quidditch who wrote (157)	4/17/2002 9:41:25 AM
From: scaram(o)uche	Read Replies (2) \| Respond to of 598

Nat Struct Biol 2002 Apr 15; [epub ahead of print] Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. Shiau AK, Barstad D, Radek JT, Meyers MJ, Nettles KW, Katzenellenbogen BS, Katzenellenbogen JA, Agard DA, Greene GL. [1] The Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA. [2] Tularik Inc., Two Corporate Drive, South San Francisco, California 94080, USA. The R,R enantiomer of 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC) exerts opposite effects on the transcriptional activity of the two estrogen receptor (ER) subtypes, ERalpha and ERbeta. THC acts as an ERalpha agonist and as an ERbeta antagonist. We have determined the crystal structures of the ERalpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ERbeta LBD bound to THC. THC stabilizes a conformation of the ERalpha LBD that permits coactivator association and a conformation of the ERbeta LBD that prevents coactivator association. A comparison of the two structures, taken together with functional data, reveals that THC does not act on ERbeta through the same mechanisms used by other known ER antagonists. Instead, THC antagonizes ERbeta through a novel mechanism we term 'passive antagonism'.