EM574
(Synonyms: Idremcinal) 目录号 : GC45446
A motilin receptor agonist
Cas No.:110480-13-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
EM574 is a motilin receptor agonist with an IC50 value of 6.17 nM for binding to rabbit gastric antral smooth muscle homogenates in a radioligand binding assay.1 It also binds to human smooth muscle homogenates in a radioligand binding assay (Kd = 7.8 nM).2 EM574 induces contraction of isolated rabbit, but not rat or guinea pig, intestine (EC50 = 5.5 nM).1 It increases antral motility and enhances gastric emptying in canine models of gastroparesis when administered intraduodenally at a dose of 0.03 mg/kg following a semi-solid meal.3
References
1. Sato, F., Sekiguchi, M., Marui, S., et al. EM574, an erythromycin derivative, is a motilin receptor agonist in the rabbit. Eur. J. Pharmacol. 322(1), 63-71 (1997).
2. Satoh, M., Sakai, T., Fujikura, K., et al. EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum. J. Pharmacol. Exp. Ther. 271(1), 574-579 (1994).
3. Sato, F., Marui, S., Inatomi, N., et al. EM574, an erythromycin derivative, improves delayed gastric emptying of semi-solid meals in conscious dogs. Eur. J. Pharmacol. 395(2), 165-172 (2000).
| Cas No. | 110480-13-2 | SDF | |
| 别名 | Idremcinal | ||
| Canonical SMILES | CC[C@H]([C@](O)(C)[C@H](O)[C@@H](C)C1=C(C)C[C@](O1)(C)[C@]([H])(O[C@@]2([H])[C@H](O)[C@@H](N(C(C)C)C)C[C@@H](C)O2)[C@@H](C)[C@@](O[C@]3([H])O[C@@H](C)[C@H](O)[C@](C)(OC)C3)([H])[C@H]4C)OC4=O | ||
| 分子式 | C39H69NO12 | 分子量 | 744 |
| 溶解度 | DMSO: soluble,Ethanol: soluble,Methanol: soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3441 mL | 6.7204 mL | 13.4409 mL |
| 5 mM | 0.2688 mL | 1.3441 mL | 2.6882 mL |
| 10 mM | 0.1344 mL | 0.672 mL | 1.3441 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
EM574, an erythromycin derivative, is a motilin receptor agonist in the rabbit
Eur J Pharmacol 1997 Mar 12;322(1):63-71.PMID:9088872DOI:10.1016/s0014-2999(96)00983-1.
This study was performed to examine whether an erythromycin derivative, de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) is a motilin receptor agonist in the rabbit gastrointestinal tract. EM574 and porcine motilin induced contractions in segments of isolated rabbit intestine with pEC50 values of 8.26 +/- 0.04 and 8.69 +/- 0.07, respectively, but not in rat or guinea pig preparations. The sensitivity and efficacy of the response to both compounds in rabbits decreased aborally and was insensitive to pretreatment with atropine or tetrodotoxin, but was markedly suppressed under Ca(2+)-free conditions. EM574 and porcine motilin specifically displaced [125I-Tyr23]canine motilin bound to gastric antral smooth muscle homogenates with plC50 values of 8.21 +/- 0.13 and 9.20 +/- 0.11, respectively. The pEC50 value for the contractile response and plC50 value for the receptor binding for motilin, EM574, erythromycin A and three other derivatives correlated well (r = 0.94, P < 0.01). Tissue section autoradiography in the antrum revealed that specific labeled motilin binding sites were localized in the circular muscle layer and myenteric plexus, and could be reduced in the presence of an excess of EM574. These results indicate that EM574 is a potent motilin receptor agonist in the rabbit gastrointestinal tract.
EM574, an erythromycin derivative, is a potent motilin receptor agonist in human gastric antrum
J Pharmacol Exp Ther 1994 Oct;271(1):574-9.PMID:7965757doi
Erythromycin and its derivatives are known to induce phase III-like contractions, which are similar to those induced by motilin, in the human gastrointestinal tract during the interdigestive state, but few detailed in vitro studies have been reported. We evaluated EM574, an erythromycin derivative, as a motilin receptor agonist in the human gastric antrum in vitro, using contraction studies of muscle strips and isolated myocytes, receptor binding assay and tissue section autoradiography. EM574 stimulated contractions of muscle strips in a concentration-dependent manner (10(-7)-10(-5) M), and this contractile effect was unaffected by pretreatment with atropine or tetrodotoxin. Isolated myocytes contracted in response to EM574 with a peak shortening at 10(-7) M, which was comparable to the response to motilin. EM574 displaced specifically 125I-motilin bound to smooth muscle homogenates with a Kd value of 7.8 x 10(-9) M, compared with 4.5 x 10(-9) M for motilin. Film autoradiograms showed that 125I-motilin-binding sites were localized in the muscle layers, and that the labeling disappeared in the presence of a 1000 times molar concentration of EM574. We conclude that EM574 directly stimulates smooth muscle cell contraction by acting on motilin receptors in the human gastric antrum in vitro.
EM574, an erythromycin derivative, improves delayed gastric emptying of semi-solid meals in conscious dogs
Eur J Pharmacol 2000 Apr 28;395(2):165-72.PMID:10794824DOI:10.1016/s0014-2999(00)00185-0.
The gastroprokinetic effects of de(N-methyl)-N-isopropyl-8, 9-anhydroerythromycin A 6,9-hemiacetal (EM574), a non-peptide motilin receptor agonist, were investigated in conscious dogs in a normal state and with experimentally-induced gastroparesis. Gastric emptying of semi-solid meals was assessed indirectly from acetaminophen absorption with simultaneous recording of gastric antral motility. In the normal state, post-prandial intraduodenal administration of EM574 (0.03 mg/kg) [corrected] stimulated antral motility and significantly enhanced gastric emptying as potently as did intravenous porcine motilin (0.003 mg/kg/h). Intraduodenal cisapride at 1 mg/kg denal cisapride at 1 mg/kg elicited antral contractions and tended to accelerate gastric emptying but at 3 mg/kg, gastric emptying was not enhanced despite a further increase in the motor index. In dogs with gastroparesis induced by intraduodenal oleic acid or intravenous dopamine, EM574 (0.03 mg/kg) increased antral motility and reversed the delayed gastric emptying completely. Cisapride (1 mg/kg) partially ameliorated the impaired emptying under these conditions. In atropinized dogs, no acceleration of gastric emptying by EM574 was observed. These results indicate that EM574 potently accelerates gastric emptying of caloric meals in dogs in a normal state and with experimentally-induced gastroparesis, and also suggest that the effect is mediated through stimulation of a cholinergic neural pathway.
Bioactive metabolites of EM574 and EM523, erythromycin derivatives having strong gastrointestinal motor stimulating activity
J Antibiot (Tokyo) 1996 Aug;49(8):794-801.PMID:8823513DOI:10.7164/antibiotics.49.794.
Two motilides, EM574 (N-demethyl-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal) and EM523 (N-demethyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal) have strong gastrointestinal motor stimulating (GMS) activity. When administered orally to dogs, these agents showed strong GMS activity, but their plasma levels were very low and the metabolites which have been determined so far using the radio-labeled compounds show only weak GMS activity. The findings suggested that unknown bioactive metabolites might be responsible for the GMS activity. From the liver of dogs given EM574 intravenously, two bioactive metabolites, EM574 P1 and P2, were isolated by solvent extraction and chromatography as detected by contractile activity. They both showed the same UV spectra as EM574 and the molecular ion peaks at m/z 760 (MH+) and 602 (MH(+)-cladinose) in the FAB-MS. From 2D-NMR experiments, the structures of EM574 P1 and P2 were unveiled to be the 15- and 14-hydroxyl derivatives of EM574, respectively. EM523 P1 and P2 were also isolated in the same procedure. In order to prepare these bioactive metabolites, EM574 and EM523 were converted enzymatically with dog liver homogenates in the presence of co-enzymes to give the corresponding P1 and P2. The structures of the metabolites are shown in Fig 1. They exhibited stronger contractile activity in vitro and GMS activity in vivo than the parent compounds.
Effects of EM574 and cisapride on gastric contractile and emptying activity in normal and drug-induced gastroparesis in dogs
J Pharmacol Exp Ther 1998 Nov;287(2):712-9.PMID:9808701doi
EM574, an erythromycin derivative and potent motilin receptor agonist, is now undergoing clinical trials as a gastroprokinetic drug. The aim of this study was to compare the effect of EM574 with that of cisapride on gastric motility and emptying in normal and gastroparesis dogs. Six dogs were each implanted with two duodenal cannulas for infusion of phenolsulfonphthalein into the proximal duodenum and for aspiration of luminal samples from the distal duodenum. Both solid and liquid gastric emptying were determined by a novel freeze-drying method developed in our laboratory. A freeze-dried standard meal (100 g, 400 kcal) was given with 100 ml normal saline containing 15 g of polyethylene glycol as a liquid marker. Gastric muscle contractility was measured by means of a force transducer implanted on the gastric antrum. EM574 (3-30 microgram/kg) and cisapride (0.3-3.0 mg/kg) were administered intraduodenally at the start of feeding. Clonidine (3-30 microgram/kg) was injected subcutaneously 15 min before feeding to induce gastroparesis. EM574 and cisapride both enhanced gastric muscle contractility in a dose-dependent manner. EM574 (30 microgram/kg and 10 microgram/kg) significantly accelerated gastric emptying of solids and liquids, respectively. Cisapride (1 mg/kg) significantly accelerated solid gastric emptying, but 3.0 mg/kg significantly delayed liquid gastric emptying. Clonidine (10 and 30 microgram/kg) significantly delayed solid and liquid gastric emptying and reduced gastric muscle contractility. EM574, at a dose of 30 microgram/kg, completely restored solid and liquid gastric emptying and muscle contractility to the normal range in dogs with clonidine-induced gastroparesis. Cisapride (1 mg/kg) restored liquid gastric emptying in dogs with gastroparesis to the normal range and partially restored solid emptying. EM574 accelerated gastric muscle contractility and emptying of solids and liquids in normal dogs. The stimulating activity of EM574 on gastric muscle contractility and emptying was comparable to that of cisapride, but EM574 was as effective as cisapride in normalizing gastric muscle contractility and emptying in dogs with clonidine-induced gastroparesis.