Reversible Lipidization Prolongs the Pharmacological Effect, Plasma Duration, and Liver Retention of Octreotide

Abstract

REAL-OCT has a significantly enhanced pharmacological effect, and this is most likely due to the favorable changes in the pharmacokinetic parameters upon lipidization. The observed liver targeting effect of REAL-TOC suggests that REAL-OCT might be advantageous over OCT in treating liver cancers.

Converting Peptides into Drug Leads by Lipidation

“…Amide Enkephalin [11][12][13], Galanin [14][15][16][17][18], GIP [7,19], GLP-1 (liraglutide) [20], hPP [21], IGF1R JM inhibitor [22], Insulin [23][24][25][26][27][28][29]; Leuteinizing hormone releasing hormone (LHRH) [30], NPW [31], NPY [15], NT [15], RC-160 [32,33], STAT3 [34], Tetragastrin [35][36][37], Thyrotropin releasing hormone (TRH) [28,30,38,39] linear Ester Angiotensin II [40,41], BBI [42][43][44], Desmopressin [45], Ghrelin [2,[46][47][48], Salmon calcitonin (sCT) [49][50][51], TRH [52], Octreotide [53] Fatty acid branched Liraglutid...…”

“…Lipidated peptides [Tyr 3 ]REAL-octreotide (Fig. 8c) [53], Mal-sCT [50] and [K 68 (EPam)]SDF1α ( Fig. 8d; SDF1α, stromal cell-derived factor-1α) [126] were more stable (2 to 12-fold) than their parent peptides in liver slices, liver fluid and liver homogenates, respectively.…”

Influence of Acylation on the Adsorption of Insulin to Hydrophobic Surfaces

“…Today, an acylated insulin variant and an acylated GLP-1 variant are marketed, while acylation has been reported to increase the plasma half-life of leu-enkephalin (12), desmopressin (13,14), octreotide (15), salmon calciotonin (16) and interferon-alpha (17).…”

Aqueous-Soluble, Non-Reversible Lipid Conjugate of Salmon Calcitonin: Synthesis, Characterization and In Vivo Activity

“…To confer the benefits of lipidization without sacrificing efficacy, Shen_s group designed a novel method, known as reversible aqueous lipidization (REAL), in which water-soluble lipid groups were conjugated to a peptide drug via inter-disulfide bonds (9Y12). This method has been shown to be particularly useful for potentiating the activity of peptide drugs with an intra-disulfide bond, such as desmopressin (10,11), calcitonin (12) and octreotide (13). The potentiated activities appeared to be related to the enhanced stability of the conjugates and their capacity to bind to local tissues and plasma proteins.…”