857066-90-1 Usage
Biological Activity
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 ofpeak 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.
Check Digit Verification of cas no
The CAS Registry Mumber 857066-90-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,5,7,0,6 and 6 respectively; the second part has 2 digits, 9 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 857066-90:
(8*8)+(7*5)+(6*7)+(5*0)+(4*6)+(3*6)+(2*9)+(1*0)=201
201 % 10 = 1
So 857066-90-1 is a valid CAS Registry Number.
857066-90-1Relevant articles and documents
Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121)
Bonfanti, Jean-Fran?ois,Meyer, Christophe,Doublet, Frédéric,Fortin, Jér?me,Müller, Philippe,Queguiner, Laurence,Gevers, Tom,Janssens, Peggy,Szel, Heidi,Willebrords, Rudy,Timmerman, Philip,Wuyts, Koen,Van Remoortere, Pieter,Janssens, Frans,Wigerinck, Piet,Andries, Koen
, p. 875 - 896 (2008/09/19)
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.