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 : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Biotech Jim who wrote (23098)	7/13/1998 12:58:00 PM
From: Pseudo Biologist	Respond to of 32384

Biotech Jim, Re. <<Well, we go from a question I raised several months ago to a Science paper. I guess the data I like most is that the compound appears to be a full agonist (fig. 6), but not according to fig. 5. Does it block natural G-CSF activity? >> Thanks for the comments, and for alerting the thread to this work in the first place. The paper answers many questions, but raises a few new ones as well. An explanation for the "biphasic" shape of the curves on figures 2 and 5 is given in the next to last paragraph of the paper. The behavior is compatible with a "direct dimerization" model where the drug crosslinks two receptor molecules. Note also the symmetric structure of the molecule (Fig. 1). I understand that this direct crosslinkig mechanism is how human growth hormone works (ref. 2), and that biphasic curves are seen in that case too. G-CSF appears to form a 2:2 complex (2 hormones, 2 receptors), and thus does not present biphasic behavior. Figure 6 does not show biphasic behavior, but this is in vivo. Hard to tell what's going on exactly here. Your last question is an interesting one; I would guess no, based on the reported experiments with mixed mouse/human extracellular domains. The last sentence of the first paragraph on page 259 reads: "This (inactivity of SB 247464 towards a construct in which only the N-terminal domains of the receptor is mouse; Fig 4 C,D) shows that the murine G-CSF receptor sequences required for SB 247464 activity are distinct from those required for G-CSF binding." PB