TMC353121Potent RSV fusion inhibitor CAS# 857066-90-1 |
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Quality Control & MSDS
3D structure
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| Cas No. | 857066-90-1 | SDF | Download SDF |
| PubChem ID | 11249932 | Appearance | Powder |
| Formula | C32H42N6O3 | M.Wt | 558.71 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 50 mg/mL (89.49 mM; Need ultrasonic) H2O : < 0.1 mg/mL (insoluble) | ||
| Chemical Name | 2-[[6-[[2-(3-hydroxypropyl)-5-methylanilino]methyl]-2-(3-morpholin-4-ylpropylamino)benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol | ||
| SMILES | CC1=CC(=C(C=C1)CCCO)NCC2=CC3=C(C=C2)N=C(N3CC4=C(C=CC(=N4)C)O)NCCCN5CCOCC5 | ||
| Standard InChIKey | DKORMNNYNRPTBJ-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C32H42N6O3/c1-23-6-9-26(5-3-16-39)28(19-23)34-21-25-8-10-27-30(20-25)38(22-29-31(40)11-7-24(2)35-29)32(36-27)33-12-4-13-37-14-17-41-18-15-37/h6-11,19-20,34,39-40H,3-5,12-18,21-22H2,1-2H3,(H,33,36) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | TMC353121 is a potent inhibitor of respiratory syncytial virus (RSV) fusion with pEC50 value of 9.9. | |||||
| Targets | RSV | |||||
| IC50 | 9.9 (pEC50) | |||||
TMC353121 Dilution Calculator
TMC353121 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.7898 mL | 8.9492 mL | 17.8984 mL | 35.7967 mL | 44.7459 mL |
| 5 mM | 0.358 mL | 1.7898 mL | 3.5797 mL | 7.1593 mL | 8.9492 mL |
| 10 mM | 0.179 mL | 0.8949 mL | 1.7898 mL | 3.5797 mL | 4.4746 mL |
| 50 mM | 0.0358 mL | 0.179 mL | 0.358 mL | 0.7159 mL | 0.8949 mL |
| 100 mM | 0.0179 mL | 0.0895 mL | 0.179 mL | 0.358 mL | 0.4475 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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TMC353121 is a RSV fusion inhibitor. It has been developed from the precursor molecule JNJ-2408068 using a molecular modelling approach. It maintains high activity (pEC50 9.9) and low cytotoxicity, while presenting a shorter retention time in the lung (lung t1/2 25 h). [1]
TMC353121 was found to inhibit RSV by preventing both virus cell fusion and syncytia formation by causing a local disturbance of the natural six-helix bundle conformation of RSV-F protein.
TMC353121 reduces viral load in therapeutic and prophylactic administration. TMC353121 has potent antiviral properties in vivo in a BALB/c mice model and protects against lung infection and virus-induced inflammation.[2]
TMC353121 had dose-dependent antiviral activity, which varied from 1log10 reduction of
peak viral load to complete inhibition of the RSV replication. TMC353121 (0.39 μg/mL) can completely inhibit the shedding of RSV. And a dose-dependent reduction of INFγ, IL6 and MIP1α was associated. TMC353121 administered as CI for 16 days was generally well-tolerated. [3]
References:
1. Bonfanti JF, Meyer C, Doublet F et al. Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121). J Med Chem. 2008; 51: 875–896.
2. Olszewska W1, Ispas G, Schnoeller C et al. Antiviral and lung protective activity of a novel respiratory syncytial virus fusion inhibitor in a mouse model. Eur Respir J. 2011 Aug;38(2):401-8.
3. Ispas G, Koul A, Verbeeck J et al. Antiviral Activity of TMC353121, a Respiratory Syncytial Virus (RSV) Fusion Inhibitor, in a Non-Human Primate Model. PLoS One. 2015 May 26;10(5):e0126959.
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Antiviral Activity of TMC353121, a Respiratory Syncytial Virus (RSV) Fusion Inhibitor, in a Non-Human Primate Model.[Pubmed:26010881]
PLoS One. 2015 May 26;10(5):e0126959.
BACKGROUND: The study assessed the antiviral activity of TMC353121, a respiratory syncytial virus (RSV) fusion inhibitor, in a preclinical non-human primate challenge model with a viral shedding pattern similar to that seen in humans, following continuous infusion (CI). METHODS: African green monkeys were administered TMC353121 through CI, in 2 studies. Study 1 evaluated the prophylactic and therapeutic efficacy of TMC353121 at a target plasma level of 50 ng/mL (n=15; Group 1: prophylactic arm [Px50], 0.033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 24 hours pre-infection to 10 days; Group 2: therapeutic arm [Tx50], 0.033 mg/mL TMC353121 from 24 hours postinfection to 8 days; Group 3: control [Vh1] vehicle, 24 hours post-infection to 8 days). Study 2 evaluated the prophylactic efficacy of TMC353121 at target plasma levels of 5 and 500 ng/mL (n=12; Group 1: prophylactic 5 arm [Px5], 0.0033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 72 hours pre-infection to 14 days; Group 2: prophylactic 500 arm [Px500], 0.33 mg/mL TMC353121; Group 3: control [Vh2] vehicle, 14 days). Bronchoalveolar lavage fluid and plasma were collected every 2 days from day 1 postinfection for pharmacokinetics and safety analysis. FINDINGS: TMC353121 showed a dose-dependent antiviral activity, varying from 1 log10 reduction of peak viral load to complete inhibition of the RSV replication. Complete inhibition of RSV shedding was observed for a relatively low plasma exposure (0.39 mug/mL) and was associated with a dose-dependent reduction in INFgamma, IL6 and MIP1alpha. TMC353121 administered as CI for 16 days was generally well-tolerated. CONCLUSION: TMC353121 exerted dose-dependent antiviral effect ranging from full inhibition to absence of antiviral activity, in a preclinical model highly permissive for RSV replication. No new safety findings emerged from the study.
Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121).[Pubmed:18254606]
J Med Chem. 2008 Feb 28;51(4):875-96.
A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.
