Rilpivirine
(Synonyms: 利匹韦林; R278474; TMC278; DB08864) 目录号 : GC11059
A non-nucleoside reverse transcriptase inhibitor
Cas No.:500287-72-9
Sample solution is provided at 25 µL, 10mM.
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Rilpivirine is a second-generation non-nucleoside inhibitor of HIV-1 reverse transcriptase with IC50 value of 0.73 nM [1].
Since the existed anti-HIV compound efavirenz showed a serious of side effects including low genetic barrier to resistance and causing CNS disturbance, the alternative NNRTIs (non-nucleoside reverse transcriptase inhibitors) with the advantages (potent, well-tolerated and long plasma half-lives) of efavirenz and without these side effects have been developed. Rilpivirine is one of these new candidate compounds [2].
Rilpivirine showed inhibitory activities to both wild-type HIV (with EC50 value of 0.51 nM) and NNRTI-resistant strains. The conformational flexibility of rilpivirine allowed it to adjust different mutations of the reverse transcriptase. For the singly mutant HIV strains such as L100I, G190S, G190A and V106A, rilpivirine showed higher retained potency than efavirenz and low EC50 values blow 1 nM. In MT-4 cells infected with the K103N isolates, rilpivirine exerted the EC50 value of 0.35 nM. Besides that, rilpivirine showed EC50 values of 2.7 nM and 0.8-1.7 nM for the double-mutant strains K103N/L100I and K103N/ Y181C, respectively. Besides that, rilpivirine was found to significantly inhibit the expression or function of some drug transporters including OATP1B1, CYP3A4 and ABCB1 [2 and 3].
The long elimination half-life and high oral bioavailability of rilpivirine allowed it to be administrated in once-daily oral dose. It showed good oral absorption at dose up to 200 mg in the in vivo evaluation assay. Since rilpivirine has a poor water- and oil- solubility, a nanosuspension injectable formulation has been developed [2 and 4].
References:
[1] Moss D M, Liptrott N J, Curley P, et al. Rilpivirine inhibits drug transporters ABCB1, SLC22A1, and SLC22A2 in vitro. Antimicrobial agents and chemotherapy, 2013, 57(11): 5612-5618.
[2] Garvey L, Winston A. Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. 2009.
[3] Weiss J, Haefeli W E. Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. International journal of antimicrobial agents, 2013, 41(5): 484-487.
[4] Baert L, van’t Klooster G, Dries W, et al. Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment. European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72(3): 502-508.
| Cell experiment [1]: | |
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Cell lines |
Caco-2 cell lines |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 h; 20 μM |
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Applications |
The ability of rilpivirine to inhibit ABCB1-mediated transport of digoxin was assessed using Caco-2 cell monolayers. Permeation of 1 μM digoxin in the A-to-B direction was significantly increased when it was coincubated with rilpivirine at 1 μM, 3μM, 10μM and 30μM compared with that for the rilpivirine-free controls. Permeation of 1 μM digoxin in the B-to-A direction was significantly decreased when it was coincubated with 10 μM rilpivirine and 30 μM rilpivirine compared with rilpivirine-free control incubations |
| Animal experiment [2]: | |
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Animal models |
Six male beagle dogs |
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Dosage form |
Per dog, two vials each containing 25 mg of TMC278; oral taken |
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Applications |
In dogs, TMC278 (rilpivirine) was more slowly absorbed from tablets than from the suspended powders for reconstitution. Compared to the tablet, the relative bioavailability obtained with the powders ranged between 69% and 89% for TMC278/PVP-VA 64 1:9 (w/w) and between 85% and 157% for TMC278/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Moss D M, Liptrott N J, Curley P, et al. Rilpivirine inhibits drug transporters ABCB1, SLC22A1, and SLC22A2 in vitro[J]. Antimicrobial agents and chemotherapy, 2013, 57(11): 5612-5618. [2] Van Gyseghem E, Pendela M, Baert L, et al. Powder for reconstitution of the anti-HIV-1 drug TMC278–formulation development, stability and animal studies[J]. European journal of pharmaceutics and biopharmaceutics, 2008, 70(3): 853-860 | |
| Cas No. | 500287-72-9 | SDF | |
| 别名 | 利匹韦林; R278474; TMC278; DB08864 | ||
| 化学名 | 4-[[4-[4-[(E)-2-cyanoethenyl]-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile | ||
| Canonical SMILES | CC1=CC(=CC(=C1NC2=NC(=NC=C2)NC3=CC=C(C=C3)C#N)C)C=CC#N | ||
| 分子式 | C22H18N6 | 分子量 | 366.42 |
| 溶解度 | ≥ 12.25 mg/mL in DMSO, ≥ 6.58 mg/mL in EtOH with ultrasonic and warming | 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 | 2.7291 mL | 13.6455 mL | 27.2911 mL |
| 5 mM | 0.5458 mL | 2.7291 mL | 5.4582 mL |
| 10 mM | 0.2729 mL | 1.3646 mL | 2.7291 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet