Disease relevance of Ditekiren

• Development of activity assays for high-volume evaluation of human immunodeficiency virus (HIV) protease inhibitors in rat serum: results with ditekiren [1].
• The cleanup methodology also enabled a commercially available Proteinase Scintillation Proximity Assay (SPA, Amersham) to quantify ditekiren in rat serum through the addition of recombinant HIV-1 protease and cleavage of substrate from SPA beads [1].

High impact information on Ditekiren

• In contrast, ditekiren, a linear hexapeptide, readily and preferentially inhibited SPGP efflux of calcein-AM [2].
• Determination of dissociation constants of high affinity (pM) human renin inhibitors: application to analogues of ditekiren (U-71,038) [3].
• These findings indicate that the biliary excretion of ditekiren and possibly other hydrophobic oligopeptides is mediated, in part, by P-glycoprotein and suggest a possible physiological role for this hepatic transporter [4].
• These findings demonstrate that both the initial uptake into hepatocytes and the subsequent biliary excretion of a linear oligopeptide, such as ditekiren, are nonlinear [5].
• In vitro evaluation of the plasma and blood compatibility of a parenteral formulation for ditekiren, a novel renin inhibitor pseudopeptide [6].

Biological context of Ditekiren

• A fluorescent human renin inhibitor, dansyl-Phe-His-LVA-Ile-Amp (3, U-80,825), was synthesized and utilized in a fluorescence energy transfer displacement assay to determine the dissociation constants (kd's) of a series of ditekiren analogues [3].
• A dose-additive blood pressure response was also observed when the administration of captopril was preceded by ditekiren in conscious sodium replete monkeys [7].

Anatomical context of Ditekiren

• Studies of 28- and 30-day infusion durations revealed intravascular precipitation in monkeys using drug solutions and rates of infusion that were expected to be precipitation-free, based on the solubility of ditekiren and assumptions about blood flow in the monkey right internal jugular vein [8].

Associations of Ditekiren with other chemical compounds

• Appraisal of a glycopeptide cloaking strategy for a therapeutic oligopeptide: glycopeptide analogs of the renin inhibitor ditekiren [9].

Gene context of Ditekiren

• The linear, hydrophobic pseudo-hexapeptide ditekiren, a renin inhibitor, is one such example [10].

Analytical, diagnostic and therapeutic context of Ditekiren

• Determination of ditekiren, a renin inhibitor peptide, in monkey serum using high-performance liquid chromatography with solid-phase extraction [11].
• Results obtained by turbidimetry indicated that formulated ditekiren did not cause aggregation of human platelets or flocculation of proteins at concentrations approaching the solubility limit of the drug in plasma [6].
• The minimum detectable limit of ditekiren for both the RIA and the bioassay for primates was 10ng/ml serum [12].
• Results were confirmed by HPLC or by the renin assay for ditekiren, which inhibits both aspartyl proteases [1].
• Oral administration of ditekiren to rats receiving human renin infusions evoked dose-dependent hypotensive responses that were greater in magnitude and longer in duration than those elicited in rats receiving hog renin infusions [13].

References