Summary

Name:

TMC353121

Synonyms:

TMC-353121; TMC 353121

Sponsor:

Janssen Therapeutics (formerly Tibotec) / Janssen Pharmaceuticals / Johnson & Johnson (global presence)

Type of product:

Inhibitor

Viral family:

Paramyxoviridae

Status:

Preclinical

Structure

Structure TMC353121

Formula:

C32H42N6O3

Molecular weight:

558.71

TMC353121 

Synonyms:TMC-353121; TMC 353121       Sponsor:Janssen Therapeutics (formerly Tibotec) / Janssen Pharmaceuticals / Johnson & Johnson (global presence)       Type of product:Inhibitor       Mode of action:EI       Viral family:Paramyxoviridae       Virus:RSV (Respiratory Syncytial virus)      

Details

Characteristics:

Small molecule, morpholinopropylaminobenzimidazole derivative acting as inhibitor of RSV F protein, blocking fusion of viral envelope with cytoplasmic membrane of host cell thereby interfering with viral entry;

 

Because of its lipophilic nature and weak basic properties, cpnd is believed to become in acidic cell compartments (e.g., lysosomes), resulting in high concentrations in lysosome-rich tissues such as those of lung and liver

PK Data, Dosage or Route of Administration:

See Rouan et al., Antimicrob Agents Chemother. 2010 Nov;54(11):4534-9. doi: 10.1128/AAC.00643-10 for details on PK/PD of TMC353121

In vivo and clinical data:

In animal studies, cotton rats received nanocrystal formulation of cpnd in s.c. doses of 12.5, 25, 50, 100, and 200 mg/kg 24 h before virus inoculation;

Four days later, bronchoalveolar lavage fluid samples were collected and RSV titers were determined by plaque and qRT-PCR assays;

Viral load in untreated control animals was 5.6 log10 PFU/ml of lung epithelial lining fluid;

Compared to titers of untreated control rats, significant (P values < 0.05) reductions of 0.2, 0.3, 0.4, 0.8, and 1.2 log10 PFU/ml of lung epithelial lining fluid were measured by plaque assay and of 0.5, 0.6, 1.1, 1.7, and 2.2 log10 PFU/ml of lung epithelial lining fluid were measured by qRT-PCR assay after administration of above-mentioned doses, respectively

Ref.: Rouan et al., Antimicrob Agents Chemother. 2010 Nov;54(11):4534-9. doi: 10.1128/AAC.00643-10

Activity in vitro

EC50: 0.125 nM (0.07 ng/mL)(RSV LO strain, HeLa cells)

Ref.: Bonfanti et al., J. Med. Chem. 51:875-896, 2008

Development status

Preclinical

Remarks

Novel cpnd for potential treatment of RSV infection



Formula: C32H42N6O3
Molecular weight: 558.71