Pleconaril (VP 63843)
(Synonyms: 普可那利,VP 63843; Win 63843) 目录号 : GC32067
A capsid-binding antipicornaviral agent
Cas No.:153168-05-9
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
Pleconaril is an antipicornaviral agent.1,2 It inhibits Picornaviridae viral replication by binding to a hydrophobic pocket in the major VP1 capsid protein, which prevents uncoating of the viral RNA genome. Pleconaril inhibits replication of the rhinoviruses HRV-A2 and HRV-B14 in HeLa Rh cells (EC50s = 0.1 and 0.3 μM, respectively) and is not cytotoxic to HeLa Rh cells with a 50% cytotoxic concentration (CC50) of greater than 131 μM.3 It also inhibits replication of enterovirus 71 (EV71) in human rhabdomyosarcoma (RD) cells (EC50 = 15 μM) and is not cytotoxic to RD cells (CC50 = >131 μM). Pleconaril (80 mg/kg per day) increases survival of EV71-infected mouse pups from 20 to 80%.4
1.Florea, N.R., Maglio, D., and Nicolau, D.P.Pleconaril, a novel antipicornaviral agentPharmacotherapy23(3)339-348(2003) 2.Bernard, A., Lacroix, C., Cabiddu, M.G., et al.Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compoundsAntivir. Chem. Chemother.24(2)56-61(2015) 3.Bernard, A., Lacroix, C., Cabiddu, M.G., et al.Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compoundsAntivir. Chem. Chemother.24(2)56-61(2015) 4.Zhang, G., Zhou, F., Gu, B., et al.In vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infectionArch. Virol.157(4)669-679(2012)
| Cas No. | 153168-05-9 | SDF | |
| 别名 | 普可那利,VP 63843; Win 63843 | ||
| Canonical SMILES | FC(C1=NC(C2=CC(C)=C(OCCCC3=CC(C)=NO3)C(C)=C2)=NO1)(F)F | ||
| 分子式 | C18H18F3N3O3 | 分子量 | 381.35 |
| 溶解度 | DMSO : 100 mg/mL (262.23 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 2.6223 mL | 13.1113 mL | 26.2226 mL |
| 5 mM | 0.5245 mL | 2.6223 mL | 5.2445 mL |
| 10 mM | 0.2622 mL | 1.3111 mL | 2.6223 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。
Single oral dose escalation pharmacokinetics of Pleconaril (VP 63843) capsules in adults
J Clin Pharmacol 1999 Jun;39(6):613-8.PMID:10354965DOI:10.1177/00912709922008227.
Pleconaril is an orally active broad-spectrum antipicornaviral agent with excellent penetration into the central nervous system and nasal epithelium. The authors report the results of a randomized, placebo-controlled, dose escalation study of pleconaril oral capsules following single-dose administration of 50 to 1000 mg. Fifty-six healthy adults (ages 19-55) participated in the study. Each subject received a single dose of pleconaril oral capsule(s) or an identically matched placebo. Blood samples (n = 19) were obtained over 36 hours postdose, and pleconaril was quantified from plasma by gas chromatography. Pleconaril disposition was best characterized using a two-compartment open-model with first-order absorption. Fifty-five subjects completed the study (31 +/- 10 years, 77.6 +/- 11 kg). The administration of pleconaril was well tolerated. There was no difference in tmax, lambda z, ka, t1/2elim, Cl/F, or Vdss/F among the various dose groups. A significant difference in both Cmax and AUC was observed between study groups; however, this difference became insignificant when the parameters were corrected for dose. Cmax and AUC were dose proportional between 50 and 1000 mg (r2 > 0.97 and 0.90, respectively). Pleconaril demonstrates a favorable safety and pharmacokinetic profile following single-dose administration.
Pleconaril: a novel antipicornaviral drug
Expert Opin Investig Drugs 2001 Feb;10(2):369-79.PMID:11178348DOI:10.1517/13543784.10.2.369.
Pleconaril (VP-63843) 3-[3,5-dimethyl-4[[3-(3-methyl-5-isoxazolyl)propyl] oly]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole is a novel, broad spectrum antipicornaviral agent. Pleconaril binds to a hydrophobic pocket in the viral capsid inducing conformational changes, which lead to altered receptor binding and viral uncoating. Pleconaril is orally bioavailable and achieves serum concentrations in excess of those required to inhibit 90% of clinical rhino- and enteroviral isolates in vitro. It possesses the additional advantage of achieving several fold higher concentrations within the central nervous system and nasal secretions than in serum, a characteristic that is highly desirable for an antiviral targeted towards viruses known to cause central nervous system and upper respiratory tract infections. Approximately 80% of an orally administered dose is excreted in the faeces within 48 h. Urine excretion accounts for the remainder of the drug. Pleconaril has demonstrated an excellent safety profile in dose escalation and clinical studies. Clinical studies have reported a reduction in the duration and intensity of symptoms in children and adults with enteroviral meningitis and in adults with rhinoviral respiratory tract infections treated with Pleconaril. Lastly, Pleconaril has demonstrated efficacy in the treatment of severe life-threatening enteroviral infections of the newborn and in immunosuppressed individuals. Pleconaril appears to be a promising drug for the treatment of enteroviral and rhinoviral infections.
Attenuated virulence of pleconaril-resistant coxsackievirus B3 variants
J Infect Dis 1999 Jun;179(6):1538-41.PMID:10228078DOI:10.1086/314758.
Pleconaril (VP 63843) is a novel orally bioavailable small molecule with broad antipicornavirus (enterovirus and rhinovirus) activity. Ten independently derived pleconaril-resistant variants of coxsackievirus B3 were isolated from cell culture. The molecular basis of drug resistance and the biologic properties of the drug-resistant viruses were investigated. RNA sequence analysis revealed amino acid changes in the drug-binding pocket of the resistant variants. Thermal stability studies showed the drug-resistant viruses to be significantly less stable than wild type virus. When evaluated in a murine model in which wild type virus infection is 100% lethal, the drug-resistant viruses showed attenuated virulence with both reduced mortality and delayed time to death. Virus titers in heart and spleen were dramatically lower in drug-resistant virus-infected mice than in wild type virus-infected animals. The study results indicate that pleconaril-resistant virus variants are attenuated and significantly less virulent than drug-sensitive wild type virus.