Compound | Chemistry |
---|---|
Lixisenatide (AVE0010, ZP10), ZP10A (see below)a | Once daily, phase III (Lyxumia) (Gerich et al., 2010). For ZP10, a prolonged-release formulation exists (Thorkildsen et al., 2003) and is going to be evaluated. |
CJC-1131 | GLP-1 analog (GLP-1 plus Gly37 replaced with Lys37, Lys37 contains a reactive chemical linker, Ala8 replaced with D-Ala8; structure in Leger et al., 2004); it allows for covalent binding to endogenous serum albumin and is protected against DPP-4 degradation (Guivarch et al., 2004); its half-life is similar to that of circulating albumin, approximately 10 to 15 days (De León et al., 2006; Nauck and Meier, 2005; Sinclair and Drucker, 2005; Christensen and Knop, 2010): no longer in active clinical development |
CJC-1134 | A similar conjugate of albumin as CJC-1131, albeit with exendin-4 (Baggio and Drucker, 2007; Baggio et al., 2008; Christensen and Knop, 2010). It is given once weekly, in phase II; the half-life of albumin is the basis of the half-life of the compound |
CJC-1134-PC | Same molecule as CJC-1134 except that it originates from exendin-4(1–39) instead of GLP-1 (Baggio et al., 2008) |
LY307161 | 31-amino acid analog of GLP-1; long acting (sustained release formulation) (Gromada et al., 2004) |
LY315902 | GLP-1 plus C8 fatty acid chain linked to Lys34, Lys26 replaced with Arg26, His7 replaced with des-His7; half-life of 3–6 h; no new data |
LY2189265 | Phase II (Bastyr et al., 2010; Glaesner et al., 2010) |
PEG-DAPD | PEGylatedb DAPD (dual acting peptide for diabetes) = GLP-1/glucagon hybrid peptide containing a maleimide-polyethylene glycol polymer (Claus et al., 2007); no new data |
Semaglutide (NN9535) | Once weekly, phase II finished, no data available |
TH0318 | Safe in phase I clinical trial (Peri et al., 2009)c |
VRS-859 | Once monthly given (Schellenberger et al., 2009; Cleland et al., 2010) |
ZP 10Aa | Exendin-4(1–39) plus N-terminally extended with a His and C-terminally extended with six Lys residues |
ZP2929 | Dual-acting as both a GLP-1 receptor agonist and a glucagon receptor agonist (like oxyntomodulin) (DauGaard et al., 2010) |
More modifications/substitutions of GLP-1 | (Green and Flatt, 2007; Yu and Wang, 2008) |
Small molecule agonists (quinoxaline) | (Irwin et al., 2010) |
LY315902, N-(3-(1H-imidazol-4-yl)-1-oxopropyl)-26-l-arginine-34-(N6-(1-oxooctyl)-l-lysine)-8–37-glucagon-like peptide I.
↵a For this novel, rationally designed peptide (H-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK-NH2), the binding affinity for the human GLP-1 receptor is 4-fold higher than that of GLP-1 (7–36) amide (Thorkildsen et al., 2003) and an antiapoptotic effect was demonstrated (Tews et al., 2008).
↵b Pegylation (covalent linking with methoxy polyethylene glycol chains) results in several advantages (e.g., increase in half life of the parent compound), is used for at least eight remedies, and is classified by the FDA as “generally recognized as safe.”