HCV protease inhibitor faldaprevir
BI-201335
Faldaprevir (BI-201335) is a highly potent and selective Hepatitis C Virus (HCV) NS3-NS4 protease inhibitor. It has shown a good ADME profile both in vitro and in vivo, so its predicted PK profile in humans is also good. This compound is available for pre-clinical research purposes only and can be used together with the BI-1230 inhibitor, which is also available on our website. We recommend ordering both compounds for your experiments.
More information
HCV NS3 protease is a 180-amino acid chymotrypsin-like serine protease. Its function is the auto-proteolytic cleavage of HCV viral polyprotein (~3000 aa) into individual, non-structural (NS) proteins with different purposes. Thus it is an essential component of HCV replication and infectivity. The NS3 protein contains two functional domains: a serine protease- and a helicase domain. The active site of NS3 is located in the shallow and wide protein-protein interaction surface of these domains. Faldaprevir and other known NS3 inhibitors cover significant parts of this interaction surface in addition to the active site. Boehringer Ingelheim was the first company to establish proof-of-concept in humans for an HCV NS3 protease inhibitor as a treatment of HCV infection.4 Faldaprevir is a highly optimized noncovalent competitive inhibitor of NS3-NS4A proteases (HCV genotypes 1a and 1b) with Ki values in theh low nanomolar range. Values of 2 to 230 nM were measured against theh NS3-NS4A proteases of HCV genotypes 2 to 6. It is a very weak inhibitor of cathepsin B and showed no inhibition of human leukocyte elastase.
X-ray structure of HCV NS3 protease with faldaprevir (BI 201335) (PDB code: 3p8n1)
| Probe name / negative control | faldaprevir | BI-1675 |
| MW [Da]a | 869.8 | 554.6 |
| IC50 [nM]b | 5.2 | 4870 |
| EC50 [nM], replicon assay, genotype 1ac | 13 | n.a. |
| EC50 [nM], replicon assay, genotype 1bc | 7.1 | n.a. |
aFor the salt form you will get, please refer to the label on the vial and for the molecular weight of the salt, please refer to the FAQs
bEnzymatic assay, NS3-NS4A heterodimer, fluorogenic substrate, 60 min incubation
cCell-based HCVPV RNA replication Luciferase reporter assay, genotype background 1a and 1b, Huh7 cells, 72 h incubation
Faldaprevir displays good permeability in Caco-2 cells assays and a high microsomal stability.
| Probe name / negative control | faldaprevir | BI-1675 |
| logD @ pH 11 | 2.1 | n.a. |
| Solubility @ pH 7 [µg/ml] | <4 | n.a. |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 2.1 | 0.1 |
| Caco-2 efflux ratio | 0.9 | 2.5 |
| MDCK permeability PappAB @ 1µM [10-6 cm/s] | 1/20 | n.a. |
| MDCK efflux ratio | 20 | n.a. |
| Microsomal stability (human/rat/dog) [% QH] | 17 / <5.6 / <10.9 | n.d |
| Plasma Protein Binding (human/mouse/rat) [%] | 99.8 / 99.2 / 100 | n.d |
Faldaprevir was investigated as part of more than 50 clinical trials and can be regarded as a well-characterized molecule for in vivo usage. Note: As part of the opnMe, the compound is shared only for pre-clinical research purposes.
| FALDAPREVIR | RATA | DOGB |
| Clearance [mL/(min*kg)] | 20 | 2.1 |
| Mean residence time after iv dose [h] | 1.6 | 2.6 |
| tmax [h] | 1.5 | 1 |
| Vss [l/kg] | 1.9 | 0.3 |
ai.v. dose: 1.7 mg/kg; p.o. dose: 4.3 mg/kg
bi.v. dose: 1.7 mg/kg; p.o. dose: 3.4 mg/kg. For more details on PK data please see reference 3.
BI-1675 can be used as negative control although it is structurally more related to BI-1230. It is recommended to order and test all three compounds in parallel.
BI-1675 which serves as a negative control for BI-1230 and faldaprevir
Faldaprevir is highly selective against other serine/cysteine proteases1-3.
Data from selectivity assay panels currently not available.
| SELECTIVITY DATA AVILABLE | Faldaprevir | BI-1675 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BI-201335_selectivityData.xlsx
BI-1675_selectivityData_0.xlsx
X-ray structure of HCV NS3 protease with faldaprevir (BI 201335) is available (see above, PDB code: 3p8n)1
BI-1230, which is also available on opnMe.com. For a review of HCV NS3 protease inhibitors please see reference 5.
Faldaprevir (BI 201335) is a highly potent and selective HCV NS3/4A protease inhibitor especially efficacious against HCV genotype 1a/1b provided for pre-clinical research use only.
Preclinical Characterization of BI 201335, a C-Terminal Carboxylic Acid Inhibitor of the Hepatitis C Virus NS3-NS4A Protease
Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection
Cross-species absorption, metabolism, distribution and pharmacokinetics of BI 201335, a potent HCV genotype-1 NS3/4A protease inhibitor
An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus
Lamarre D., Anderson P. C., Bailey M., Beaulieu P., Bolger G., Bonneau P., Bös M., Cameron D. R., Cartier M., Cordingley M. G., Faucher A. M., Goudreau N., Kawai S. H., Kukolj G., Lagacé L., LaPlante S. R., Narjes H., Poupart M. A., Rancourt J., Sentjens R. E., St George R., Simoneau B., Steinmann G., Thibeault D., Tsantrizos Y. S., Weldon S. M., Yong C. L., Llinàs-Brunet M.
Nature 2003, 426, 186-189.
When you plan a publication, please use the following acknowledgement:
BI 201335 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.