Rupintrivir
(Synonyms: (2E,4S)-4-[(2R,5S)-2-(4-氟苄基)-6-甲基-5-(5-甲基异恶唑-3-基甲酰氨基)-4-氧代庚酰氨基]-5-[[(3S)-2-氧代-3-吡咯烷基]-2-戊烯酸乙酯,AG7088) 目录号 : GC50441
一键复制产品信息
Rupintrivir是一种强效、不可逆的human rhinovirus (HRV) 3C protease抑制剂，抑制所有HRV血清型复制的平均EC50值为0.023μM。
Cas No.:223537-30-2
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Rupintrivir is a potent, irreversible inhibitor of human rhinovirus (HRV) 3C protease with a mean EC50 value of 0.023μM for inhibiting the replication of all HRV serotypes [1]. Rupintrivir binds in a unique conformation to the active site of SARS-CoV-2 Mpro, splitting the catalytic cysteine and histidine residues and inhibiting the activity of SARS-CoV-2 [2]. Rupintrivir has been widely used to inhibit the replication of enterovirus 71 (EV 71), and is combined with IFN-α to develop combination therapies that efficiently eliminate the virus [3].
In vitro, Rupintrivir treatment for 72 hours significantly reduced the levels of Norovirus RNA in HG23 cells, with an EC50 value of 0.3µM[4]. Treatment with 100nM Rupintrivir for 48 hours suppressed the HRV-induced hypersecretion of cytokines IL-6 and IL-4 in precision-cut lung slices (PCLS) from house dust mite (HDM)-sensitized mice [5].
In vivo, Rupintrivir treatment via daily intraperitoneal injection at a dose of 0.1mg/kg for 10 days can alleviate EV 71 virus-induced necrotizing myositis in suckling mice and increase the survival rate[6].
References:
[1] Patick A K, Binford S L, Brothers M A, et al. In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease[J]. Antimicrobial agents and chemotherapy, 1999, 43(10): 2444-2450.
[2] Lockbaum G J, Henes M, Lee J M, et al. Pan-3C protease inhibitor rupintrivir binds SARS-CoV-2 main protease in a unique binding mode[J]. Biochemistry, 2021, 60(39): 2925-2931.
[3] Hung H C, Wang H C, Shih S R, et al. Synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir[J]. Journal of Infectious Diseases, 2011, 203(12): 1784-1790.
[4] Rocha-Pereira J, Nascimento M S J, Ma Q, et al. The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon[J]. Antimicrobial agents and chemotherapy, 2014, 58(8): 4675-4681.
[5] Danov O, Lasswitz L, Obernolte H, et al. Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo[J]. Respiratory research, 2019, 20(1): 228.
[6] Zhang X, Song Z, Qin B, et al. Rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: evaluation of antiviral efficacy in a murine infection model[J]. Antiviral research, 2013, 97(3): 264-269.
Rupintrivir是一种强效、不可逆的human rhinovirus (HRV) 3C protease抑制剂，抑制所有HRV血清型复制的平均EC50值为0.023μM[1]。Rupintrivir以独特的构象结合到SARS-CoV-2 Mpro的活性位点，将催化半胱氨酸和组氨酸残基分开，从而抑制SARS-CoV-2的活性[2]。Rupintrivir已被广泛用于抑制肠道病毒 71型(EV 71)的复制，并与IFN-α联合开发可有效清除病毒的联合疗法[3]。
在体外，Rupintrivir处理HG23细胞72小时，显著降低了诺如病毒(Norovirus)RNA的水平，EC50值为0.3μM[5]。100nM的Rupintrivir处理48小时，抑制了屋尘螨(HDM)致敏小鼠的精确切割肺切片(PCLS)中HRV诱导的细胞因子IL-6和IL-4的过度分泌[5]。
在体内，每日腹腔注射0.1mg/kg剂量的Rupintrivir，连续10天，可减轻EV 71病毒诱导的乳鼠坏死性肌炎，并提高存活率[6]。
| Cell experiment [1]: | |
Cell lines | HG23 cells |
Preparation Method | HG23 cells (Norwalk virus replicon-bearing Huh-7 origin) were grown in RPMI-1640 medium with 10% (v/v) fetal bovine serum (FBS), 2mM l-glutamine, 20mM HEPES, 0.075g/l sodium bicarbonate, 100U penicillin/ml, and 100μg/ml streptomycin at 37°C and 1.25mg/ml of Geneticin (G418) in a humidified atmosphere of 5% CO2. Cells were seeded in 96-well plates at a density of 5×103 cells and cultured overnight. A serial dilution of Rupintrivir (0.1, 0.2, 0.4, 0.8, 1.6, 3.1, and 6.3µM) was added to the cultures. After 72h of incubation, cell monolayers were washed with phosphate-buffered saline (PBS) and collected for quantification of RNA load by qRT-PCR. |
Reaction Conditions | 0.1, 0.2, 0.4, 0.8, 1.6, 3.1, and 6.3µM; 72h |
Applications | Rupintrivir treatment significantly reduced the levels of Norovirus RNA in HG23 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Suckling ICR mice |
Preparation Method | Two-day-old suckling ICR mice (2.0-2.3g) were injected with 106 pfu EV71 (strain 695F) and subsequently underwent intraperitoneal (i.p.) injection with 5-15μl of Rupintrivir or ribavirin dissolved in DMSO to achieve a dosage of 0.1mg/kg (n=13) for Rupintrivir or 100mg/kg (n=10) for ribavirin; an equivalent volume of DMSO was injected in the control group (n=14). The Rupintrivir was injected every day for 10 days. Infected mice were monitored daily for signs of morbidity and mortality. The sickness of mice was evaluated using a graded score (0, healthy; 1, slow movement; 2, weakness in hind limbs; 3, paralysis in single limb; 4, paralysis in two limbs; and 5, death). |
Dosage form | 0.1mg/kg/day for 10 days; i.p. |
Applications | Rupintrivir treatment effectively rescued EV71-induced paralysis and death in a suckling mouse model. |
References: | |
| Cas No. | 223537-30-2 | SDF | |
| 别名 | (2E,4S)-4-[(2R,5S)-2-(4-氟苄基)-6-甲基-5-(5-甲基异恶唑-3-基甲酰氨基)-4-氧代庚酰氨基]-5-[[(3S)-2-氧代-3-吡咯烷基]-2-戊烯酸乙酯,AG7088 | ||
| Canonical SMILES | O=C(C1=NOC(C)=C1)N[C@@H](C(C)C)C(C[C@@H](CC2=CC=C(F)C=C2)C(N[C@H](/C=C/C(OCC)=O)C[C@@H]3CCNC3=O)=O)=O | ||
| 分子式 | C31H39FN4O7 | 分子量 | 598.66 |
| 溶解度 | DMSO : 50 mg/mL (83.52 mM; Need ultrasonic) | 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 | 1.6704 mL | 8.352 mL | 16.704 mL |
| 5 mM | 334.1 μL | 1.6704 mL | 3.3408 mL |
| 10 mM | 167 μL | 835.2 μL | 1.6704 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet