Rilpivirine (Synonyms: R278474, TMC278) |
| カタログ番号GC11059 |
非ヌクレオシド逆転写酵素阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| 同義語 | R278474, TMC278 | ||
| Chemical Name | 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 | ||
| Formula | C22H18N6 | M.Wt | 366.42 |
| 溶解度 | ≥ 12.25 mg/mL in DMSO, ≥ 6.58 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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