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OBJECTIVE The aim of the present study was to identify a small, metabolically stable somatotropin release inhibiting factor (SRIF) analog with a more universal binding profile similar to that of natural somatostatin, resulting in improved pharmacological properties and hence new therapeutic uses. DESIGN A rational drug design approach was followed by(More)
Stepwise modification of a conformationally stabilised analogue of the fragment of somatostatin which had been thought to be essential biologically active moiety has enabled us to synthesise the analogue H-(D) Phe-Cys-Phe-(D) Trp-Lys-Thr-Cys-Thr(ol) code-named SMS 201-995, which in vitro is three times more potent than the native hormone in inhibiting the(More)
The goal of this project was to find a somatostatin (SRIF) analog with superior therapeutic potential. Receptor binding studies of new SRIF analogs were used to reveal SRIF substructures that interact with individual human SRIF receptor subtypes (sst1-sst5). Incorporation of these substructures into a stable cyclohexapeptide template led to SOM230, which(More)
The aim of the present study was to selectively target a beta-emitter-labelled octreotide analogue to somatostatin (SRIF)-receptor-expressing tumours and to evaluate the feasibility of SRIF-receptor-mediated radiotherapy by delivering a lethal dose of radiation to the tumour. The most promising compound in a series of DTPA-coupled octreotide analogues was(More)
To obtain orally active octreotide (Sandostatin, SMS 201-995) analogs a new class of glycated somatostatin derivatives were synthesized by the Amadori reaction (Maillard reaction). The synthesis, chemical and biological characterization of a series of new compounds is described. These oligopeptides bind with high affinity to somatostatin receptors and(More)
Starting from a hypothetical conformation of natural somatostatin and a knowledge of the minimal fragment needed for biological activity, a process of rational design and lead optimization has led to the potent, selective, and long-acting analogue SMS 201-995, (formula: see text) which selectively inhibits growth hormone secretion in several animal species(More)
Somatostatin (SRIF) and its octapeptide analogue, octreotide (Sandostatin), have a similar high affinity for specific receptors with 50% inhibitory concentrations (IC50s) in the subnanomolar range. Hence, the striking superiority of octreotide in vivo, which includes duration of action, specificity, and potency, must originate from its different(More)
An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe1 of Tyr3-octreotide. This new(More)
Magnetic resonance imaging (MRI) has been used for the determination in vivo of rat pituitary size. In midsagittal T2-weighted sections the pituitary, having a lower T2 value than the surrounding tissue, was visible with pronounced contrast. The size has been estimated by pixel counting. A close correlation (r = 0.96) with the pituitary weights determined(More)