Chlorcyclizine
(Synonyms: 氯环利嗪；氯环力嗪) 目录号 : GC63666
A histamine H1 antagonist
Cas No.:82-93-9
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Rats[1]Timed-mated CRL:CD [SD] female rats between 9 and 13 weeks of age at initiation of dosing and weighing between 245 and 363 g are used. Rats are administered a single daily oral gavage dose of 30, 60, or 90 mg/kg Chlorcyclizine (n=8/group) during the sensitive period for palate development, GDs 11 to 14. These doses are selected such that 30 mg/kg is a likely no-effect dose and higher doses of 60 and/or 90 mg/kg will induce a moderate or high incidence of fetal cleft palate. Given that CRL:CDs [SD] rats have an extremely low incidence of spontaneous cleft palate in the testing laboratory, as well as to avoid unnecessary use of animals, a methylcellulose control group is omitted[1].
[1]. Enright BP, et al. Effects of the histamine H1 antagonist Chlorcyclizine on rat fetal palate development. Birth Defects Res B Dev Reprod Toxicol. 2010 Dec;89(6):474-84.
Chlorcyclizine is a phenylpiperazine that acts as a histamine H1 receptor antagonist (Ki = 9 nM).1 It has also been shown to be effective against hepatitis C virus (HCV; EC50 = 44 nM in vitro), preventing viral entry into host cells.2 In chimeric mice engrafted with primary human hepatocytes, 10-50 mg/kg chlorcyclizine significantly inhibited infection of HCV genotypes 1b and 2a.2
1.Tran, V.T., Chang, R.S.L., and Snyder, S.H.Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramineProc. Natl. Acad. Sci. USA75(12)6290-6294(1978) 2.He, S., Xiao, J., Dulcey, A.E., et al.Discovery, optimization, and characterization of novel chlorcyclizine derivatives for the treatment of hepatitis C virus infectionJ. Med. Chem.59(3)841-853(2016)
| Cas No. | 82-93-9 | SDF | |
| 别名 | 氯环利嗪；氯环力嗪 | ||
| 分子式 | C18H21ClN2 | 分子量 | 300.83 |
| 溶解度 | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.3241 mL | 16.6207 mL | 33.2414 mL |
| 5 mM | 0.6648 mL | 3.3241 mL | 6.6483 mL |
| 10 mM | 0.3324 mL | 1.6621 mL | 3.3241 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。
Chlorcyclizine Inhibits Viral Fusion of Hepatitis C Virus Entry by Directly Targeting HCV Envelope Glycoprotein 1
Cell Chem Biol 2020 Jul 16;27(7):780-792.e5.PMID:32386595DOI:10.1016/j.chembiol.2020.04.006.
Chlorcyclizine (CCZ) is a potent hepatitis C virus (HCV) entry inhibitor, but its molecular mechanism is unknown. Here, we show that CCZ directly targets the fusion peptide of HCV E1 and interferes with the fusion process. Generation of CCZ resistance-associated substitutions of HCV in vitro revealed six missense mutations in the HCV E1 protein, five being in the putative fusion peptide. A viral fusion assay demonstrated that CCZ blocked HCV entry at the membrane fusion step and that the mutant viruses acquired resistance to CCZ's action in blocking membrane fusion. UV cross-linking of photoactivatable CCZ-diazirine-biotin in both HCV-infected cells and recombinant HCV E1/E2 protein demonstrated direct binding to HCV E1 glycoprotein. Mass spectrometry analysis revealed that CCZ cross-linked to an E1 sequence adjacent to the putative fusion peptide. Docking simulations demonstrate a putative binding model, wherein CCZ binds to a hydrophobic pocket of HCV E1 and forms extensive interactions with the fusion peptide.
Carrier mediated transport of chlorpheniramine and Chlorcyclizine across bovine olfactory mucosa: implications on nose-to-brain transport
J Pharm Sci 2005 Mar;94(3):613-24.PMID:15666293DOI:10.1002/jps.20284.
Delivery to the CNS via the nasal cavity has been pursued as a means to circumvent the blood-brain barrier (BBB), yet the mechanism of drug transport across this novel route is not well understood. Hydroxyzine and triprolidine have been reported to readily reach the CNS following nasal administration, whereas no measurable amounts of Chlorcyclizine or chlorpheniramine, structurally similar antihistamines, were observed in the CSF. The permeation of chlorpheniramine and Chlorcyclizine in vitro across the bovine olfactory mucosa was studied to investigate the biological and physicochemical characteristics that contribute to the limited CNS disposition of these compounds following nasal administration. The submucosal to mucosal fluxes (J(s-m)) of Chlorcyclizine and chlorpheniramine across the olfactory mucosa were significantly greater than the mucosal to submucosal fluxes (J(m-s)). Moreover, the submucosal-mucosal permeability of both compounds was temperature dependent and saturable. In the presence of metabolic inhibitors (ouabain and 2,4-dinitrophenol) and P-glycoprotein (P-gp)/multidrug resistance protein 1 (MRP1) inhibitors (quinidine and verapamil), the J(m-s) increased and J(s-m) decreased significantly. These results indicate that chlorpheniramine and Chlorcyclizine are effluxed from the olfactory mucosa by efflux transporters such as P-gp and MRP1. Transport studies across inert polymeric membranes demonstrated that the permeability of chlorpheniramine and Chlorcyclizine decreased at donor concentrations higher than 3 mM suggesting that physicochemical properties such as self-aggregation also play a role in the reduced olfactory mucosal permeability of these compounds at higher concentrations.
Chlorcyclizine--induced pulmonary phospholipidosis in rats
Res Commun Chem Pathol Pharmacol 1982 Nov;38(2):235-46.PMID:6131507doi
Chlorcyclizine (CZ) was administered to rats (100 mg/kg, p.o.) for either 1 or 2 weeks (5 days per week). Controls were pair-fed and received deionized water vehicle for the same periods of time. The level of total phospholipid increased about 50% in the lungs after 1 week of CZ but did not increase further after 2 weeks of treatment. There was a time-dependent increase in the recovery of alveolar macrophages (AMs) from the lungs of the CZ-treated rats as well as in the phospholipid content of the cells. After 2 weeks of CZ, the AMs contained 5.6-fold more phospholipid than controls. The AM fraction showed a greater relative elevation in phospholipid at both time points than did the remainder of the lung tissue. The results illustrated the marked susceptibility of the AM to the disruption of phospholipid metabolism by CZ.
Effects of the histamine H1 antagonist Chlorcyclizine on rat fetal palate development
Birth Defects Res B Dev Reprod Toxicol 2010 Dec;89(6):474-84.PMID:21058326DOI:10.1002/bdrb.20261.
Background: The effects of histamine H1 antagonist Chlorcyclizine on rat palate development were characterized following in utero exposure. Methods: To identify the optimum dose for inducing cleft palate, pregnant rats were administered 30, 60, or 90 mg/kg Chlorcyclizine on Gestation Days 11 to 14. Fetal palate gene expression was also assessed after 90 mg/kg Chlorcyclizine at 8, 15 and 30 hours post-dose on Gestation Day 14 using microarray and qRT-PCR. Results: Rats in the 60- and 90-mg/kg groups exhibited adverse clinical signs and body weight loss. Rats in the 90-mg/kg group also demonstrated increases in late resorptions and decreases in fetal weight. Effects in the low-dose group were limited to decreases in body weight gain. Fetal assessment on Gestation Day 21 revealed that findings were limited to the 60- and 90-mg/kg groups, and included cleft palate (80% of litters for both groups), high arched palate, small nose, micrognathia, high domed head, digits shortened/absent and small limb. The fetal incidence of cleft palate was higher at 90 mg/kg, thus this dose was selected to assess palate gene expression. The altered genes associated with chlorcyclizine-induced cleft palate included Wnt5a, Bmp2, Bmp4, Fgf10, Fgfr2, Msx1, and Insig1 but the magnitude of the change was relatively small (1.5- to 2-fold). Conclusions: Expression of several genes involved in palate, limb and digit development was altered in the fetal palate following in utero exposure to Chlorcyclizine. The subtle perturbation and interplay of these genes may have profound effects on the dynamics of fetal palate development.
Preclinical Pharmacological Development of Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection
J Infect Dis 2018 May 5;217(11):1761-1769.PMID:29373739DOI:10.1093/infdis/jiy039.
Hepatitis C virus (HCV) is a small, single-stranded, positive-sense RNA virus that infects more than an estimated 70 million people worldwide. Untreated, persistent HCV infection often results in chronic hepatitis, cirrhosis, or liver failure, with progression to hepatocellular carcinoma. Current anti-HCV regimens comprising direct acting antivirals (DAAs) can provide curative treatment; however, due to high costs there remains a need for effective, shorter-duration, and affordable treatments. Recently, we disclosed anti-HCV activity of the cheap antihistamine Chlorcyclizine, targeting viral entry. Following our hit-to-lead optimization campaign, we report evaluation of preclinical in vitro absorption, distribution, metabolism, and excretion properties, and in vivo pharmacokinetic profiles of lead compounds. This led to selection of a new lead compound and evaluation of efficacy in chimeric mice engrafted with primary human hepatocytes infected with HCV. Further development and incorporation of this compound into DAA regimens has the potential to improve treatment efficacy, affordability, and accessibility.