The BioWorld article on Ligand's G-CSF was good size. It took up 1/4 of page 1 and all of page 3. The article was entitled "Ligand Finds Mini-Molecule To Do G-CSF Protein's Job". The byline is "Mantra For Drug Discovery: Pill, Yes; Needle No" and was written by David Leff.
The article begins be mentioning the biotechnology and pharma's version of a needle exchange program which seeks to find oral compounds capable of replacing injected drugs. Rosen is quoted extensively throughout the report (he was senior author on the Science paper and Senior Director of Transcription Research at Ligand.
Background on AMGN's billion dollar a year injectable G-CSF (Nuepogen) is given and Ligand and partner SBH have "drawn a bead on G-CSF as a likely first target of their aim to replace large proteins with mini-mimic molecules.
The mimic, SB247464, was discovered in SBH's defined compound collection. It "is a symetrical, heterocyclic, organic compound with a molecular weight of 526 daltons."
The paper indicates that a compound such as a small molecule that can be taken orally has several advantages over the large protein or smaller peptides (5K), both of which require injection.
The molecule is thought to work via receptor oligomerization, but SB247464 is mouse specific (unlike recombinant Neupogen which works on mouse and human receptors).
The only real info on other molecules came from this paragraph:
"Although this compound does have, we believe, incredible effects in the mouse," Rosen observed, "in the assays we've done to date we have not seen activity in human systems. so we're going back to several drawing boards, looking for related molecules from the same series as well as discovery of additional ones that will be human-active."
Ligand plans to use SB247464 to study its mechanism of action by testing some hypotheses on how it actually works.
in the final paragraph:
Rosen concluded, "This is a general approach to drug discovery that's applicable to many protein receptor systems. It's an important lesson that we learned - and I'm afraid many others will learn from our work."
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