Camicinal  (Synonyms: GSK962040)

Camicinal (GSK962040) is a small molecule, selective motilin receptor agonist with pEC50 of 7.9.

pEC50: 7.9 (Motilin Receptor)^[1].

Camicinal (GSK962040) had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, Camicinal (GSK962040) 300 nmol L 1-10 μmol L 1 caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol L 1. The pEC50 values for motilin, erythromycin and Camicinal (GSK962040) were, respectively, 10.4 ± 0.01 (n = 770), 7.3 ± 0.29 (n = 4) and 7.9 ± 0.09 (n = 17) [1]. Camicinal (GSK962040) activated the dog motilin receptor (pEC50 5.79; intrinsic activity 0.72, compared with [Nle13]-motilin) [2]. Camicinal (GSK962040) was preferred because its initial IC₅₀ values at CYP3A4 were significantly higher than our preferred threshold of 10 μM [3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Camicinal (GSK962040) (5 mg free base kg 1) also produced an increase in total faecal weight over the 2-h postdose period (21.2 ± 4.5 g; P < 0.05) [1]. Camicinal (GSK962040) induced phasic contractions, the duration of which was dose-related (48 and 173 min for 3 and 6 mg kg 1), driven by mean plasma concentrations >1.14 μmol L 1. After the effects of GSK962040 faded, migrating motor complex (MMC) activity returned. Migrating motor complex restoration was unaffected by 3 mg kg 1 GSK962040 but at 6 mg kg 1, MMCs returned 253 min after dosing, compared with 101 min after saline (n = 5 each) [2]. he oral bioavailability (Fpo) of Camicinal (GSK962040) was found to be 48 ( 13%. Camicinal (GSK962040) shows a long lasting effect (T1/2 ) 46.9 ( 5.0 min at 3 μM) when compared with the short-lived effect of [Nle13]motilin (T1/2 ) 11.4 ( 1.5 min at 0.3 μM) [3]. Camicinal (GSK962040) strongly facilitated cholinergic activity in the antrum, with lower activity in fundus and small intestine only [4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

424.55

Solid

C₂₅H₃₃FN₄O

923565-21-3

O=C(N1CCC(NC2=CC=CC(F)=C2)CC1)CC3=CC=C(CN4C[C@H](C)NCC4)C=C3

Room temperature in continental US; may vary elsewhere.

• [1]. Sanger, G.J., et al., GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil, 2009. 21(6): p. 657-64, e30-1.  [Content Brief]

  [2]. Leming, S., et al., GSK962040: a small molecule motilin receptor agonist which increases gastrointestinal motility in conscious dogs. Neurogastroenterol Motil, 2011. 23(10): p. 958-e410.  [Content Brief]

  [3]. Westaway, S.M., et al., Discovery of N-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-pi peridinamine (GSK962040), the first small molecule motilin receptor agonist clinical candidate. J Med Chem, 2009. 52(4): p. 1180-9.  [Content Brief]

  [4]. Broad, J., et al., Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists. Br J Pharmacol, 2012. 167(4): p. 763-74.  [Content Brief]