HCV protease inhibitor
BI-1230
BI-1230 is a single-digit nanomolar inhibitor of HCV NS3 protease activity and of viral replication. It binds to the active site of NS3 and was shown to be highly selective against other serine/cysteine proteases. BI-1230 shows good in vivo PK properties, including half-life and bioavailability. As such, this compound is a valuable tool for both in vitro and in vivo studies. We also offer faldaprevir from our infectious diseases pipeline for pre-clinical research purposes.
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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 various functions. 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. BI-1230 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 infection4.
| Probe name / negative control | BI-1230 | BI-1675 |
| MW [Da, free base]a | 817.0 | 554.6 |
| IC50 [nM]b | 6.7 | 4870 |
| EC50 [nM], replicon assay, genotype 1ac | 4.6 | n.d. |
| EC50 [nM], replicon assay, genotype 1bc | <1.8 | n.d. |
a For 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
b Enzymatic assay, NS3-NS4A heterodimer, fluorogenic substrate, 60 min incubation
c Cell-based HCVPV RNA replication Luciferase reporter assay, genotype background 1a and 1b, Huh7 cells, 72h incubation
| Probe name | BI-1230 | BI-1675 |
| logD @ pH 11 | 2.7 | 0.4 |
| Solubility @ pH 7 [µg/mL] | >39 | n.d. |
| Caco-2 permeability AB @ pH 7.4 [*10-6 cm/s] | 8.7 | 0.1 |
| Caco efflux ratio | 0.3 | 2.5 |
| Microsomal stability [% QH] | <24 | n.d. |
| Plasma Protein Binding human [%] | 99.9 | n.d. |
| CYP 1A2 (IC50) [µM] | 13.9 | n.d. |
| CYP 2C9 (IC50) [µM] | 4 | n.d. |
| CYP 2C19 (IC50) [µM] | 2 | n.d. |
| CYP 2D6 (IC50) [µM] | >30 | n.d. |
in vivo DMPK parameters of BI-1230 in rat and doga.
| Route | BI-1230 | RATA | DOGB |
| i.v. | Clearance [mL/min/kg] | 15 | 1.9 |
| Mean residence time after i.v. dose [h] | 2.3 | 3.4 | |
| Vss [L/kg] | 2.1 | 0.4 | |
| p.o. | t1/2 [h] | 2.1 | 5.1 |
| tmax [h] | 1.8 | 1.7 | |
| Cmax [nM] | 405 | 7370 | |
| AUC0-inf [nM*h] | 2550 | 49700 | |
| F [%] | 42 | 92 |
a i.v. dose: 1.6 mg/kg, p.o. dose: 4 mg/kg
b i.v. dose: 1.1 mg/kg, p.o. dose: 2.2 mg/kg
BI-1675 can be used as inactive in vitro control compound.
BI-1675, negative control
BI-1230 is highly selective against other serine/cysteine proteases.
| SELECTIVITY DATA AVILABLE | BI-1230 | BI-1675 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| PDSP6 | Yes | Yes |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
Download selectivity data:
BI-1230_selectivityData.xlsx
BI-1675_selectivityData.xlsx
An X-ray structure of BI-1230 in complex with NS3 is not available. However, the structure with the highly related faldaprevir (BI 201335) was solved.
X-ray structure of HCV NS3 protease with faldaprevir, a close analog of BI-1230 (PDB code: 3p8n)
For a recent review of HCV NS3 protease inhibitors see reference 5.
BI-1230 is a nanomolar inhibitor of Hepatitis C Virus (HCV) protease and of viral replication with good in vivo PK characteristics.
A Highly Convergent and Efficient Synthesis of a Macrocyclic Hepatitis C Virus Protease Inhibitor BI 201302
Wei X., Shu C., Haddad N., Zeng X., Patel N. D., Tan Z., Liu J., Lee H., Shen S., Campbell S., Varsolona R. J., Busacca C. A., Hossain A., Yee N. K., Senanayake C. H.
Org. Lett. 2013, 15, 1016-1019.
WO 2005/028501A1, US 8552205
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-1230 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.