YM 022

[Description]:

YM022 is a highly potent, selective and orally active gastrin/cholecystokinin (CCK)-B receptor (CCK-BR) antagonist. YM022 shows the Ki values of 68 pM and 63 nM for CCK-B and CCK-A receptor, respectively[1]. YM022 can inhibit gastrin-induced gastric acid secretion and histidine decarboxylase activation in vivo[3].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> CCR

Signaling Pathways >> Immunology/Inflammation >> CCR

Research Areas >> Metabolic Disease

[Target]

CCR1:68 pM (Ki)

CCR2:63 nM (Ki)

[In Vitro]

YM022 inhibits binding to canine pancreas CCK-A receptor in a dose-dependent manner, with an IC50 value for [3H]devazepide binding of 136 nM[1]. YM022 inhibits the binding of [125I]CCK-8 to canine cloned gastrin/CCK-B receptor in a dose-dependent manner, with an IC50 value for [125I]CCK-8 binding of 0.73 nM[1]. Selectivity [ratio of (IC50 for gastrin/CCK-B receptor)/(IC50for CCK-A receptor)] of YM022 is 186[1].

[In Vivo]

YM022 (intravenous injection; 0.01-1 μM/kg) dose-dependently inhibits pentagastrin- and peptone meal-induced acid secretion with ED50 values of 0.0261 and 0.0654 μmol/kg, respectively, without affecting histamine- or methacholine-induced acid secretion[3]. YM022 (subcutaneous injection; 300 μmol/kg; single dose) lowers the oxyntic mucosal HDC activity and raises the serum gastrin concentration in a dose-dependent manner (measured 24 h after dosage). Maximum enzyme inhibition is achieved at a dose of 300 μmol/kg for YM022 and the inhibition of HDC lasts for 4 weeks. At sacrifice, drug residues can be seen at the injection site for as long as 4 (YM022) weeks after injection in rat[3]. YM022 is suspended in 2% Methocel for oral ingestion and in PEG300 for subcutaneous injection[3]. Animal Model: Rat[3] Dosage: 300 μmol/kg Administration: Subcutaneous injection; 300 μmol/kg; single dose Result: Suppressed the ECL cell activity for at least 4 as manifested in greatly reduced HDC activity, greatly elevated serum gastrin level.

[References]

[1]. Nishida A, et al. Pharmacological profile of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo- 5-phenyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), a new potent and selective gastrin/cholecystokinin-B receptor antagonist, in vitro and in vivo.J Pharmacol Exp Ther. 1994 May;269(2):725-31.

[2]. Kitano M, et al. Long-lasting cholecystokinin(2) receptor blockade after a single subcutaneous injection of YF476 or YM022.Br J Pharmacol. 2000 Jun;130(3):699-705.

[3]. Beinborn M, et al. Small synthetic ligands of the cholecystokinin-B/gastrin receptor can mimic the function of endogenous peptide hormones.Yale J Biol Med. 1998 May-Aug;71(3-4):337-46.

[ Density]:
1.23g/cm3

[ Boiling Point ]:
735.4ºC at 760mmHg

[ Melting Point ]:
187-190 °C

[ Molecular Formula ]:
C₃₂H₂₈N₄O₃

[ Molecular Weight ]:
516.59000

[ Flash Point ]:
398.6ºC

[ Exact Mass ]:
516.21600

[ PSA ]:
90.87000

[ LogP ]:
5.48260

[ Vapour Pressure ]:
1.72E-21mmHg at 25°C

[ Index of Refraction ]:
1.647

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301

[ Precautionary Statements ]:
P301 + P310

[ Hazard Codes ]:
T+

[ RIDADR ]:
UN 2811 6.1 / PGIII

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