E-6123
目录号 : GC35922
E-?6123 是一种血小板活化因子 (PAF) 受体拮抗剂。
Cas No.:131614-02-3
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
E-6123 is a platelet-activating factor (PAF) receptor antagonist. PAF[1]
E-6123 (E6123) partially inhibits the Thapsigargin-induced increase in the levels of interleukin-6 mRNA and interleukin-6 protein. To clarify the role of the concurrently produced cell-associated PAF in the thapsigargin-induced increase in the interleukin-6 mRNA level and interleukin-6 production, the effects of the PAF receptor antagonist E-6123 are examined. E-6123 at 1 and 10 μM partially inhibits the Thapsigargin (46.1 nM)-induced increase in the interleukin-6 mRNA level at 4 h and interleukin-6 production at 8 h[1].
[1]. Ichinowatari G, et al. Participation of prostaglandin E2 and platelet-activating factor in thapsigargin-induced production of interleukin-6. Eur J Pharmacol. 2002 Jan 11;434(3):187-96.
| Cas No. | 131614-02-3 | SDF | |
| Canonical SMILES | O=C(C1CC1)N2CC3=C(CC2)C(C(C4=CC=CC=C4Cl)=N[C@H]5C)=C(S3)N6C5=NN=C6C | ||
| 分子式 | C23H22ClN5OS | 分子量 | 451.97 |
| 溶解度 | Soluble in DMSO | 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 | 2.2125 mL | 11.0627 mL | 22.1254 mL |
| 5 mM | 0.4425 mL | 2.2125 mL | 4.4251 mL |
| 10 mM | 0.2213 mL | 1.1063 mL | 2.2125 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。
Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist
Arzneimittelforschung 1990 Nov;40(11):1201-5.PMID:2085331doi
(S)-(+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl - 2,3,4,5 - tetrahydro - 8H - pyrido[4',3':4,5] thieno[3,2-fl-[1,2,4]triazolo]4,3-a][1,4]diazepine (E-6123) is a newly synthesized platelet-activating factor (PAF) antagonist. The effects of E-6123 on in vitro and in vivo PAF-induced responses were investigated. The IC50 values of E-6123 on 3H-PAF binding to human and guinea pig platelets were 2.7 and 3.0 nmol/l, respectively, and those on PAF-induced platelet aggregation in platelet-rich plasma of human, guinea pig and beagle dog were 10.1, 14.7 and 16 nmol/l, respectively. Oral administration of E-6123 at 3 and 10 micrograms/kg to dogs inhibited ex vivo PAF-induced platelet aggregation in a dose-dependent manner. In guinea pigs, E-6123 at 3 micrograms/kg completely inhibited ex vivo PAF-induced platelet aggregation up to 8 h and the inhibition was still significant at 24 h after administration. Occupancy of the platelet PAF receptor by E-6123 at 3 h and 24 h after administration amounted to 80% and 56%, respectively. Bronchoconstriction induced by PAF injection in guinea pigs was inhibited dose-dependently by oral or intravenous administration of E-6123 at similar doses. The IC50 value of E-6123 at 3 h after oral administration was 1 microgram/kg. Oral administration of E-6123 at 3 micrograms/kg inhibited the bronchoconstriction by more than 90% up to 8 h. Hemato-concentration induced by PAF injection in guinea pigs was inhibited by oral administration of E-6123 at 10 micrograms/kg. E-6123 also protected mice from PAF injection-induced death in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Dual effects of a novel thienodiazepine platelet-activating factor antagonist, on drug-oxidizing enzymes in beagle dog
Xenobiotica 1994 Apr;24(4):293-300.PMID:8059533DOI:10.3109/00498259409045893.
1. We have examined the effects of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8, 11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3, 2-f][1, 2, 4]triazolo[4, 3-a][1, 4]diazepine (E-6123), a novel thienodiazepine platelet-activating factor antagonist, on drug-oxidizing capacity in beagle dog, using antipyrine (AP) and trimethadione (TMO) as two model substrates. 2. The plasma half-life (t1/2) and area under the curve (AUC) of AP (0.5 mg/kg, i.v. injection) increased in a dose-dependent manner after a single oral dose of E-6123 (0.2, 1 or 10 mg/kg), whereas the total body clearance (Cl) of AP was decreased, and the apparent volume of distribution (Vd) was unchanged. 3. The pharmacokinetic parameters (t1/2, Cl and AUC) of the metabolism of TMO (4 mg/kg, i.v.) after repeated oral administration of E-6123 (10 mg/kg for 7 days) were not significantly changed in comparison with findings in control dog. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO in plasma after i.v. administration of TMO in E-6123-treated dog was increased only 5 and 15 min after the final dose, but was not changed at other sampling times (0.5, 1, 2 4, 6, 8 and 12 h). 4. The content of b5, the activity of p-nitroanisole O-demethylase and benzphetamine N-demethylase were significantly increased, compared with controls, by repeated E-6123 treatment. However, aniline hydroxylase activity was not significantly changed. 5. Content of P450 2B was significantly increased in E-6123 treated dog, while that of 3A was not.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist. Effects on microvascular permeability, hypotension and nephrosis
Arzneimittelforschung 1991 Dec;41(12):1255-9.PMID:1815526doi
The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.
PAF mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways
Am J Physiol Lung Cell Mol Physiol 2001 Mar;280(3):L436-41.PMID:11159026DOI:10.1152/ajplung.2001.280.3.L436.
Goblet cell metaplasia is an important morphological feature in the airways of patients with chronic airway diseases; however, the precise mechanisms that cause this feature are unknown. We investigated the role of endogenous platelet-activating factor (PAF) in airway goblet cell metaplasia induced by cigarette smoke in vivo. Guinea pigs were exposed repeatedly to cigarette smoke for 14 consecutive days. The number of goblet cells in each trachea was determined with Alcian blue-periodic acid-Schiff staining. Differential cell counts and PAF levels in bronchoalveolar lavage fluid were also evaluated. Cigarette smoke exposure significantly increased the number of goblet cells. Eosinophils, neutrophils, and PAF levels in bronchoalveolar lavage fluid were also significantly increased after cigarette smoke. Treatment with a specific PAF receptor antagonist, E-6123, significantly attenuated the increases in the number of airway goblet cells, eosinophils, and neutrophils observed after cigarette smoke exposure. These results suggest that endogenous PAF may play a key role in goblet cell metaplasia induced by cigarette smoke and that potential roles exist for inhibitors of PAF receptor in the treatment of hypersecretory airway diseases.
Eosinophilic airway inflammation induced by repeated exposure to cigarette smoke
Eur Respir J 1998 Aug;12(2):387-94.PMID:9727790DOI:10.1183/09031936.98.12020387.
Acute exposure to cigarette smoke causes airway hyperresponsiveness (AHR) in guinea-pigs, which resolves within a few hours. Repeated exposure may have a different effect on the airways. To address this question, guinea-pigs were repeatedly exposed to cigarette smoke (six cigarettes for 1 h x day(-1)) for 14 consecutive days. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 1 day after the last exposure. Significant neutrophilia in BALF was observed after 3 days of smoke exposure. Significant eosinophilia in BALF and AHR were observed after 14 days of smoke exposure, but not after 3 or 7 days of smoke exposure. These changes persisted until 3 days after the last exposure and resolved 7 days afterwards. Histologically, the recruited eosinophils were observed predominantly in the airways, but not in the alveoli. Treatment with E-6123, a specific platelet-activating factor receptor antagonist (1 mg x kg(-1) x day(-1) p.o. during smoke exposure) significantly inhibited the eosinophil influx and AHR. Repeated exposure to cigarette smoke may induce prolonged airway inflammation and airway hyperresponsiveness in guinea-pigs. Platelet-activating factor or platelet-activating factor-like lipids may play a key role in airway hyperresponsiveness, presumably by the induction of eosinophilic airway inflammation.