|To: Pseudo Biologist who wrote (438)||6/29/1999 12:44:00 PM|
|From: Mike McFarland|
*OT chit chat|
Good discussion here of late, not sure
I understood it all, but I gave it my
best. I read it all again yesterday. With
the article in the Journal, who knows,
maybe somebody will notice Sibia soon.
I re-established my half position in
this yesterday, yes, a significant portion
of that pathetic volume was just little ol
me. Had to spend a third of my MAGN to do it,
timing was not so good, I had some magn at 1.5,
took a smidgen of gain, but could have had more
if I'd held off til today, no matter, nearly
20 grand in magn was just too much, back to
just an insane amount.
I'll go to a full position in sibi if we see
a significant dip, there are always buying
ops, but I think I want to be in this now,
espcially if the PFE cloud suddenly lifts.
Thanks to all for your opinions here,
as well as on the patent thread. I am
going to discount PFE's suit as a merely
a mechanism to keep the lawyers busy...
job security and all that. Maybe PFE is
just using it as a negiotiaing took to
snag a lower royalty rate than the others,
then they can look good against the others
paying the extravagant half percent.
Of course a half a percent of what? That
I'd like to know.
In for a penny, in for a pound. Thanks again
all, sorry I don't have anything to contribute
other than that I'm on back on board.
|RecommendKeepReplyMark as Last ReadRead Replies (2)|
|To: Jongmans who wrote (441)||7/11/1999 11:12:00 PM|
Finally, SIBI/BMY Alzheimer's collaboration will begin clinical trials by year-end. |
Thursday's report about ELN(Athena)'s work toward an Alzheimer's vaccine took all the headlines (lots of chatter on CNBC, lead stories on TV network news, WSJ and other major newspaper articles, etc), but the WSJ article also noted the good news that BMY would begin clinical trials of SIBI's anti-amyloid plaque protease inhibitor drug candidate:
"[I]f initial safety trials go well [BMY] will quickly move into large-scale tests of effectiveness. In a high-risk gambit to get a drug to market faster, the company will simultaneously conduct four large trials . . . rather than the more typical procedure of conducting consecutive rounds of efficacy trials. . . . The trials will involve several thousand patients and last as long as two years." (WSJ 7/8/99, p. A8, continuation of ELN/Alzheimer's article on front page - hardcopy, sorry, I don't access the interactive edition).
BMY will apparently be spending serious money on these trials. Its apparent strong commitment to development hasn't, I believe, been publicized before now. The 4/30/99 SIBI 10-K noted only that the "most advanced compounds from this [BMY Alzheimer's] collaboration are in pre-clinical development" [p. 10, see also table from p.6, included in post #308 on this thread Message 8680842 .
Rick Harmon's post #384 noted that SIBI IR was still saying early this month that SIBI "expected to hear of clinical plans soon" techstocks.com , Rick having earlier muttered a couple of times about how tight-lipped SIBI was being about this collaboration , e.g. techstocks.com )
On the ELN/Athena effort, see also: techstocks.com
|RecommendKeepReplyMark as Last ReadRead Replies (1)|
|To: Czechsinthemail who wrote ()||7/17/1999 1:29:00 PM|
J Pharmacol Exp Ther 1999 Jul;290(1):170-81 |
SIB-1757 and SIB-1893: selective, noncompetitive antagonists of
metabotropic glutamate receptor type 5.
Varney MA, Cosford ND, Jachec C, Rao SP, Sacaan A, Lin FF, Bleicher L, Santori EM, Flor PJ, Allgeier H,
Gasparini F, Kuhn R, Hess SD, Veli elebi G, Johnson EC
SIBIA Neurosciences, Inc., La Jolla, California.
[Medline record in process]
Cell lines expressing the human metabotropic glutamate receptor subtype 5a (hmGluR5a) and hmGluR1b were used as targets
in an automated high-throughput screening (HTS) system that measures changes in intracellular Ca2+ ([Ca2+]i) using
fluorescence detection. This functional screen was used to identify the mGluR5-selective antagonist, SIB-1757
[6-methyl-2-(phenylazo)-3-pyridinol], which inhibited the glutamate-induced [Ca2+]i responses at hmGluR5 with an IC50 of
0.37 &mgr;M compared with an IC50 of >100 &mgr;M at hmGluR1. Schild analysis demonstrated a noncompetitive
mechanism of inhibition. Pharmacophore mapping was used to identify an additional compound, SIB-1893
[(E)-2-methyl-6-(2-phenylethenyl)pyridine], which was also shown to block glutamate-induced increases in [Ca2+]i at
hmGluR5 with an IC50 of 0.29 &mgr;M compared with an IC50 of >100 &mgr;M at hmGluR1. SIB-1757 and SIB-1893
showed little or no activity when tested for agonist and antagonist activity at the other recombinant human mGluR subtypes,
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, and N-methyl-D-aspartate receptors. In rat neonatal
brain slices, SIB-1757 and SIB-1893 inhibited (S)-3,5-dihydroxyphenylglycine (DHPG)-evoked inositol phosphate
accumulation in hippocampus and striatum by 60% to 80%, with a potency similar to that observed on recombinant mGluR5.
However, in the cerebellum, a brain region with low mGluR5 expression, SIB-1757 failed to inhibit DHPG-evoked inositol
phosphate accumulation. In cultured rat cortical neurons, SIB-1757 and SIB-1893 largely inhibited DHPG-evoked [Ca2+]i
signals, revealing a population of neurons that were less sensitive to SIB-1757 and SIB-1893. This is the first description of
highly selective, noncompetitive mGluR5 antagonists. These compounds will be useful tools in evaluating the role of mGluR5 in
normal physiology and in animal models of disease.
|RecommendKeepReplyMark as Last ReadRead Replies (1)|