YM022

YM022用途

YM022 是一种高效,选择性和口服活性胃泌素/胆囊收缩素(CCK)-B 受体 (CCK-BR) 拮抗剂。 YM022 显示CCK-B 和 CCK-A 受体的 Ki 值分别为 68 pM 和 63 nM。 YM022 在体内可以抑制胃泌素诱导的胃酸分泌和组氨酸脱羧酶的活化。

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YM022名称

[ CAS 号 ]:
145084-28-2

[ 中文名 ]:
YM022

[ 英文名 ]:
YM 022

[英文别名 ]:

ym 022

YM022生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> CCR

信号通路 >> 免疫及炎症 >> CCR

研究领域 >> 代谢疾病

[ 靶点 ]

CCR1:68 pM (Ki)

CCR2:63 nM (Ki)

[体外研究]

YM022以剂量依赖的方式抑制与犬胰腺CCK-A受体的结合,[3H]去甲肾上腺素结合的IC50值为136nm[1]。YM022抑制[125I]CCK-8与犬克隆胃泌素/CCK-B受体的结合,呈剂量依赖性,其IC50值为0.73nm[1]。YM022的选择性[胃泌素/CCK-B受体的IC50与CCK-A受体的IC50之比]为186[1]。

[体内研究]

YM022(静脉注射；0.01-1μM/kg)剂量依赖性抑制五肽胃泌素和蛋白胨粉诱导的酸分泌,ED50值分别为0.0261和0.0654μmol/kg,而不影响组胺或甲基胆碱诱导的酸分泌[3]。YM022(皮下注射,300μmol/kg,单次给药)以剂量依赖的方式降低胃粘膜HDC活性,升高血清胃泌素浓度(给药后24小时测定)。对YM022的最大酶抑制率为300μmol/kg,HDC的抑制作用持续4周。牺牲时,大鼠注射后4周(YM022)内注射部位可见药物残留[3]。YM022悬浮于2%甲氧基纤维素中供口服,PEG300悬浮于皮下注射[3]。动物模型：大鼠[3]剂量：300μmol/kg给药：皮下注射；300μmol/kg；单次给药结果：抑制ECL细胞活性至少4次,表现为HDC活性大大降低,血清胃泌素水平大大升高。

[参考文献]

[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.

YM022物理化学性质

[ 密度 ]:
1.23g/cm3

[ 沸点 ]:
735.4ºC at 760mmHg

[ 熔点 ]:
187-190 °C

[ 分子式 ]:
C₃₂H₂₈N₄O₃

[ 分子量 ]:
516.59000

[ 闪点 ]:
398.6ºC

[ 精确质量 ]:
516.21600

[ PSA ]:
90.87000

[ LogP ]:
5.48260

[ 蒸汽压 ]:
1.72E-21mmHg at 25°C

[ 折射率 ]:
1.647

[ 储存条件 ]:
室温，密封，干燥

YM022安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301

[ 警示性声明 ]:
P301 + P310

[ 危害码 (欧洲) ]:
T+

[ 危险品运输编码 ]:
UN 2811 6.1 / PGIII

YM022文献

Motilin Stimulates Gastric Acid Secretion in Coordination with Ghrelin in Suncus murinus.

PLoS ONE 10 , e0131554, (2015)

Motilin and ghrelin constitute a peptide family, and these hormones are important for the regulation of gastrointestinal motility. In this study, we examined the effect of motilin and ghrelin on gastr...

Glycogen Synthase Kinase-3beta regulates Snail and beta-catenin during gastrin-induced migration of gastric cancer cells.

J. Mol. Signal. 5 , 9, (2010)

The gastrointestinal peptide hormone gastrin is known to regulate various cellular processes including proliferation, migration and metastasis in gastrointestinal (GI) cells. The studies described her...

Signaling through cholesterol esterification: a new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion.

J. Lipid Res. 50(11) , 2203-11, (2009)

Several studies indicate that cholesterol esterification is deregulated in cancers. The present study aimed to characterize the role of cholesterol esterification in proliferation and invasion of two ...

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