IHVR-19029
目录号 : GC39492
IHVR-19029 是一种有效的内质网 α-葡萄糖苷酶 Ⅰ 和 Ⅱ (α-glucosidases I/II) 抑制剂，对 ER α-葡萄糖苷酶 Ⅰ 的 IC50 为0.48 μM。IHVR-19029 能有效阻断几种出血热病毒的复制，如登革病毒、埃博拉病毒和裂谷热病毒。
Cas No.:1447464-73-4
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
IHVR-19029 is a potent endoplasmic reticulum (ER) α-glucosidases I and II inhibitor, with an IC50 of 0.48 μM for ER a-glucosidase I. IHVR-19029 efficiently blocks the replication of several hemorrhagic fever viruses, such as Dengue virus (DENV), Ebola virus (EBOV) and Rift Valley fever virus[1][2][3].
[1]. Bray M, et al. Meeting report: 31st International Conference on Antiviral Research. Antiviral Res. 2018 Oct;158:88-102. [2]. Jin hong Chang, et al. Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses. Antiviral Research. Volume 98, Issue 3, June 2013, Pages 432-440. [3]. Ester Prodrugs of IHVR-19029 with Enhanced Oral Exposure and Prevention of Gastrointestinal Glucosidase Interaction.ACS Med Chem Lett. 2017 Jan 17;8(2):157-162. [4]. Ma J, et al. Enhancing the antiviral potency of ER α-glucosidase inhibitor IHVR-19029 against hemorrhagic fever viruses in vitro and in vivo. Antiviral Res. 2018 Feb;150:112-122.
| Cas No. | 1447464-73-4 | SDF | |
| Canonical SMILES | O=C(NC(C)(C)C)N(C1CCCCC1)CCCCCCN2[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C2 | ||
| 分子式 | C23H45N3O5 | 分子量 | 443.62 |
| 溶解度 | DMSO: 250 mg/mL (563.55 mM) | 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 | 2.2542 mL | 11.2709 mL | 22.5418 mL |
| 5 mM | 0.4508 mL | 2.2542 mL | 4.5084 mL |
| 10 mM | 0.2254 mL | 1.1271 mL | 2.2542 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。
Ester Prodrugs of IHVR-19029 with Enhanced Oral Exposure and Prevention of Gastrointestinal Glucosidase Interaction
ACS Med Chem Lett 2017 Jan 17;8(2):157-162.PMID:28197304DOI:10.1021/acsmedchemlett.6b00332.
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay. Further in vitro evaluation showed that the bioconversion of the prodrugs is species dependent: in mice, the prodrugs were converted to 6 in the plasma and liver; while in human, the conversion occurred mainly in liver. An in vivo pharmacokinetic study in mice demonstrated that the tetrabutyrate prodrug 8 achieved the most improved overall exposure of 6 upon both oral and intravenous administration.
Enhancing the antiviral potency of ER α-glucosidase inhibitor IHVR-19029 against hemorrhagic fever viruses in vitro and in vivo
Antiviral Res 2018 Feb;150:112-122.PMID:29253498DOI:10.1016/j.antiviral.2017.12.008.
Targeting host functions essential for viral replication has been considered as a broad spectrum and resistance-refractory antiviral approach. However, only a few host functions have, thus far, been validated as broad-spectrum antiviral targets in vivo. ER α-glucosidases I and II have been demonstrated to be essential for the morphogenesis of many enveloped viruses, including members from four families of viruses causing hemorrhagic fever. In vivo antiviral efficacy of various iminosugar-based ER α-glucosidase inhibitors has been reported in animals infected with Dengue, Japanese encephalitis, Ebola, Marburg and influenza viruses. Herein, we established Huh7.5-derived cell lines with ER α-glucosidase I or II knockout using CRISPR/Cas9 and demonstrated that the replication of Dengue, Yellow fever and Zika viruses was reduced by only 1-2 logs in the knockout cell lines. The results clearly indicate that only a partial suppression of viral replication can possibly be achieved with a complete inhibition of ER-α-glucosidases I or II by their inhibitors. We therefore explore to improve the antiviral efficacy of a lead iminosugar IHVR-19029 through combination with another broad-spectrum antiviral agent, favipiravir (T-705). Indeed, combination of IHVR-19029 and T-705 synergistically inhibited the replication of Yellow fever and Ebola viruses in cultured cells. Moreover, in a mouse model of Ebola virus infection, combination of sub-optimal doses of IHVR-19029 and T-705 significantly increased the survival rate of infected animals. We have thus proved the concept of combinational therapeutic strategy for the treatment of viral hemorrhagic fevers with broad spectrum host- and viral- targeting antiviral agents.