Thursday, February 6, 2014
Although at least 10 companies are chasing inhibitors of
for decreasing low-density lipoprotein cholesterol, the compounds dominating
the field are antibodies or siRNAs that require injection. Roche's Genentech Inc. unit and a
separate team from Pfizer Inc. and The University of Queensland
are betting that peptides might provide an oral competitor and have identified
short peptide fragments that inhibit binding of PCSK9 to its target.1,2
Optimizing the potency and stability for oral delivery is the next challenge.
Craik and colleagues used rational drug design to create peptides that would
competitively inhibit the interaction between PCSK9 and its binding site on
LDLR, which lies in the receptor's epidermal growth factor-like A domain
Craik told SciBX that the next steps for his team
include improving the potency and biopharmaceutical properties of the peptides.
His team has not yet tested the peptides in animal models.
Martz, L. SciBX 7(5);
Published online Feb. 6, 2014
Y. et al. J. Biol. Chem.; published online Nov. 13, 2013;
Contact: Daniel Kirchhofer, Genentech Inc., South San Francisco, Calif.
2. Schroeder, C.I. et
al. Chem. Biol.; published online Jan. 16, 2014;
Contact: David J. Craik, The University of Queensland, Brisbane,
3. Kwon, H.J. et al.
Proc. Natl. Acad. Sci. USA 105, 1820-1825 (2008)
Esperion Therapeutics Inc. (NASDAQ:ESPR),
South San Francisco, Calif.
(NYSE:PFE), New York, N.Y.
(SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
Shifa Biomedical Corp., Malvern, Pa.
The University of Queensland, Brisbane, Queensland, Australia