Background:

IC50: 0.02 nM for SSTR3

Somatostatin (SRIF) is a cyclic tetradecapeptide that was originally isolated from mammalian hypothalamus and characterized as a physiological regulator of GH secretion from the anterior pituitary. BIM 23056 is a novel linear peptide of SRIF SSTR3 antagnist.

In vitro: BIM 23056 bound to SSTR3 with subnanomolar affinities. BIM 23056 displayed remarkable selectivity for SSTR3, not interacting significantly with either SSTR1 or SSTR2 at concentrations as high as 1 μM. BIM 23056 was 30,000-fold selective for SSTR3, which maks it a ligand of choice for future studies on SSTR3 [1]. In addition, it has been found that BIM 23056 behaves as a potent and surmountable antagonist at the human recombinant sst5 receptor. Such antagonism was specific for the sst5 receptor as BIM 23056 did not inhibit [Ca2+], or Ins(1,4,5)P3 increases in response to UTP [2].

In vivo: No animal in vivo data have been reported.

Clinical trial: Up to now, BIM 23056 is still in the preclinical development stage.

参考文献:
[1] Raynor K, Murphy WA, Coy DH, Taylor JE, Moreau JP, Yasuda K, Bell GI, Reisine T.  Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides. Mol Pharmacol. 1993 Jun;43(6):838-44.
[2] Wilkinson GF, Thurlow RJ, Sellers LA, Coote JE, Feniuk W, Humphrey PP.  Potent antagonism by BIM-23056 at the human recombinant somatostatin sst5 receptor. Br J Pharmacol. 1996 Jun;118(3):445-7.