RD3-0028
目录号 : GC32340
RD3-0028是有效和选择性的RSV复制抑制剂，EC50值为4.5μM。
Cas No.:3886-39-3
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
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Cell experiment: |
50 mL of HeLa cell suspensions (30000 cells/well) and the Long strain of RSV(25 TCID50/well) in MEM supplemented with 0.1% bovine serum albumin and antibiotics are added to each well in a 96-well round-bottomed microtiter plate that is filled with 50mL of MM in the presence or absence of several concentrations of RD3-0028. The anti-RSV assay is performed primarily with the MTT method[1]. |
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Animal experiment: |
Mouse: Aerosols are generated from reservoirs containing 0.3 to 7.0 mg of RD3-0028 per mL. Solutions of ribavirin are prepared in saline containing 2.5 to 60 mg/mL. Mice are treated intraperitoneally with 100 mg of cyclophosphamide per kg of body weight 5 days before virus inoculation. The mice are weighed, anesthetized with sodium pentobarbital (50 mg/kg), and inoculated intranasally with approximately 105 PFU of RSV A2 in 50 mL (day 0). From day 1 through day 3, the mice are exposed to the RD3-0028 or ribavirin aerosol. Placebo consisted of 10% DMSO-saline containing 1% Tween 80. On day 4, the day on which untreated mice had the maximum RSV pulmonary titer, all animals are killed and the lungs of each mouse are removed and for virus quantification[2].Rat: 14C-RD3-0028 is dissolved in 10% dimethyl sulphoxide (DMSO)/saline containing 1% Tween 80 for administration by the aerosol route. The aerosol is generated using a head-exposure chamber, mono-position, with a mist generator. The mass median aerodynamic diameter of the aerosol particle is 2.1 mm. Rats are exposed to the 14C-RD3-0028 aerosol for 15min and killed at indicated times after the end of exposure. Because the aerosol treatment with 14C-RD3-0028 exposed the rat to 8.8 mg (91.5 kBq)/animal, the solution of this compound is orally administered at a dose of 8.8 mg/body[3]. |
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References: [1]. Watanabe W, et al. Novel anti-respiratory syncytial(RS) viral compounds: benzodithiin derivatives. Biochem Biophys Res Commun. 1998 Aug 28;249(3):922-6. |
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RD3-0028 is a potent and selective inhibitor of RSV replication with an EC50 of 4.5 μM.
RD3-0028 has a 50% effective concentration of 4.5 μM and a 50% cytotoxic concentration of 271.0μM which is superior to that of ribavirin. RD3-0028 inhibits different RSV strains at a low concentration (4.5-11.0 μM) using the MTT method. Using the MTT method, EC50 values of RD3-0028 against tested strains are lower than those of ribavirin. RD3-0028 does not inhibit the replication of measles virus, influenza A virus, herpes simplex virus types 1 and 2, or human cytomegalovirus[1].
Aerosols generated from reservoirs containing RD3-0028 (7 mg/mL) administered for 2 h twice daily for 3 days significantly reduces the pulmonary titer of RSV-infected mice. It is clear that the minimal effective dose of RD3-0028 for RSV-infected mice is significantly less than that of ribavirin, the only compound currently available for use against RSV disease. Furthermore, the RD3-0028 aerosol administration protect the lungs of infected, CYP-treated mice against tissue damage, as evidenced by the preservation of the lung architecture and a reduction in pulmonary inflammatory infiltrates. RD3-0028 aerosol is not toxic for mice at the therapeutic dose[2]. The plasma concentration of RD3-0028 is maintained at the same level from 5 min to 1 h, and decreases with a half-life of 2.2 h for 1±8 h. The excretion of radioactivity in the urine and faeces at 24 h after aerosol treatment is 89.3 and 4.5%, respectively, indicating that almost all the radioactivity is rapidly excreted in the urine. The excretion of total radioactivity is 98.9% within 168 h[3].
[1]. Watanabe W, et al. Novel anti-respiratory syncytial(RS) viral compounds: benzodithiin derivatives. Biochem Biophys Res Commun. 1998 Aug 28;249(3):922-6. [2]. Sudo K, et al. Efficacy of RD3-0028 aerosol treatment against respiratory syncytial virus infection in immunosuppressed mice. Antimicrob Agents Chemother. 1999 Apr;43(4):752-7. [3]. Sudo K, et al. Pharmacokinetics of a benzodithiin (RD3-0028) following aerosol treatment in rat.
| Cas No. | 3886-39-3 | SDF | |
| Canonical SMILES | C12=CC=CC=C1CSSC2 | ||
| 分子式 | C8H8S2 | 分子量 | 168.28 |
| 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 | 5.9425 mL | 29.7124 mL | 59.4248 mL |
| 5 mM | 1.1885 mL | 5.9425 mL | 11.885 mL |
| 10 mM | 0.5942 mL | 2.9712 mL | 5.9425 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。
Efficacy of RD3-0028 aerosol treatment against respiratory syncytial virus infection in immunosuppressed mice
Antimicrob Agents Chemother 1999 Apr;43(4):752-7.PMID:10103176DOI:10.1128/AAC.43.4.752.
RD3-0028, a benzodithiin compound, has antiviral activity against respiratory syncytial virus (RSV) in cell culture. We used a mouse model of RSV infection to determine the in vivo effect of RD3-0028. Cyclophosphamide (CYP)-treated, immunosuppressed mice were inoculated intranasally. The lungs of the mice were removed on day 4. The virus titers of the lungs of RD3-0028-treated mice were compared to the virus titers of the lungs of virus-inoculated, untreated control mice. In an effort to increase the therapeutic effectiveness of this compound, RD3-0028 was administered by aerosol to RSV-infected mice by using a head-exposure system. Aerosols generated from reservoirs containing RD3-0028 (7 mg/ml) administered for 2 h twice daily for 3 days significantly reduced the pulmonary titer of RSV-infected mice. It is clear that the minimal effective dose of RD3-0028 for RSV-infected mice is significantly less than that of ribavirin, the only compound currently available for use against RSV disease. Furthermore, the RD3-0028 aerosol administration appeared to protect the lungs of infected, CYP-treated mice against tissue damage, as evidenced by the preservation of the lung architecture and a reduction in pulmonary inflammatory infiltrates. RD3-0028 aerosol was not toxic for mice at the therapeutic dose. The present study demonstrates the effectiveness of aerosol administration of RD3-0028 for RSV-infected mice.
Mechanism of selective inhibition of respiratory syncytial virus by a benzodithiin compound (RD3-0028)
Microbiol Immunol 2001;45(7):531-7.PMID:11529559DOI:10.1111/j.1348-0421.2001.tb02654.x.
RD3-0028, a compound with a benzodithiin structure, was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication. Its action is specific; no activity is seen against influenza A virus, measles virus, herpes simplex virus type 1 or 2, or human cytomegalovirus. A time-dependent drug addition experiment indicated that the antiviral activity occurs in the late stage of the RSV replication cycle, since this compound completely inhibited syncytium formation even when added up to 16 hr after the infection of cell monolayers at an MOI of 3. RD3-0028 had no direct virucidal effect on RSV. Western blotting analysis showed that RD3-0028 significantly decreased the amount of RSV proteins released into the cell culture medium. Moreover, five independent isolates of the RSV long strain were selected for growth in RD3-0028 (5-20 microg/ml). These resistant viruses were more than 80-fold less sensitive to RD3-0028 than the long strain. The F gene segment of each of these viruses was sequenced and in each case the mutant RNA segment contained at least one sequence alteration, converting asparagine 276 to tyrosine (F1 protein). These results suggest that RD3-0028 inhibits RSV replication by interfering with intracellular processing of the RSV fusion protein, or a step immediately thereafter, leading to loss of infectivity.
Pharmacokinetics of a benzodithiin (RD3-0028) following aerosol treatment in rat
Xenobiotica 2002 Jan;32(1):19-27.PMID:11820507DOI:10.1080/00498250110079158.
1. RD3-0028, a benzodithiin compound, has potent antiviral activity against respiratory syncytial virus (RSV) in cell culture. The compound also inhibits growth of RSV and improves pathologic changes of interstitial pneumonia in the immunosuppressed mouse when delivered by small-particle aerosol. 2. In the present study, the absorption, distribution and excretion of 14C-RD3-0028 were compared in rat following either a single aerosol treatment or oral administration. 3. The plasma concentration was maintained at the same level from 5 min to 1 h, and decreased with a half-life of 2.2 +/- 0.1 h for 1-8 h. 4. The excretion of radioactivity in the urine and faeces at 24 h after aerosol treatment was 89.3 and 4.5%, respectively, indicating that almost all the radioactivity was rapidly excreted in the urine. The excretion of total radioactivity was 98.9% within 168 h. 5. The concentrations of radioactivity in the lung and trachea following aerosol treatment were higher than those in other tissues, and were detected even at 72 h. 6. These results suggest that the aerosol treatment might be useful for delivering RD3-0028 to the respiratory tract of RSV-infected patients.
Novel anti-respiratory syncytial(RS) viral compounds: benzodithiin derivatives
Biochem Biophys Res Commun 1998 Aug 28;249(3):922-6.PMID:9731237DOI:10.1006/bbrc.1998.9222.
Benzodithiin derivatives are highly potent and specific inhibitors of respiratory syncytial virus (RSV) replication in vitro. The most potent and selective congener of a benzodithiin derivative is 1,4-dihydro-2,3-benzodithiin(RD3-0028). According to the modified 3-(4,5-dimethylthiazole-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) assay developed in our laboratories, this compound has a 50% effective concentration of 4.5 microM and a 50% cytotoxic concentration of 271.0 microM, which is superior to that of ribavirin. This compound also inhibits RSV strain subgroups A and B and clinical isolates. RD3-0028, however, does not inhibit the replication of influenza A virus, measles virus, herpes simplex virus types 1 and 2, or human cytomegalovirus. Two other benzodithiin derivatives [1,4-dihydro-6-methyl-2,3-benzodithiin (RD3-0270) and 1,4-dihydro-5-methyl-1-2,3-benzodithiin (RD3-0284)] also inhibit RSV replication at a selectivity index greater a factor of 20. These results suggest that the benzodithiin skeleton is an important structure for inhibitory activity against RSV replication.