Chymase inhibitor
BI-1942
BI-1942 is a highly potent inhibitor of human chymase (IC50 = 0.4 nM). It was tested in a panel of 37 proteases and showed more than 100-fold selectivity against Cathepsin G. This compound is a suitable tool to study the role of chymase in vitro. There is no available data regarding in vivo experiments.
More information
Chymase plays an important and diverse role in the homeostasis for a number of cardiovascular processes and has been linked to heart failure. Chymase is a chymotrypsin-like serine protease that is stored in a latent form in the secretory granules of mast cells. Upon stimulation, it is released in its active form into the local tissue, contributing to the activation of TGF-ß, matrix metalloproteases and cytokines. Cardiac chymase has been shown to be involved in the formation of angiotensin II and to play an important role in activating TGF-ß1 and IL-1ß, generating endothelin, altering apolipoprotein metabolism and degrading the extracellular matrix.
Chymase in complex with a close analog of BI-1942 (Boehringer Ingelheim internal structure).
| Probe name / negative control | BI-1942 | BI-1829 |
| MW [Da] | 434.5 | 419.5 |
| Inhibition of human chymase IC50 [nM]* | 0.4 | 850 |
a for detailed assay conditions see reference 1
| Probe name / negative control | BI-1942 | BI-1829 |
| Solubility @ pH 7.4 [µg/ml] | >93 | n.d. |
| Solubility @ pH 4.5 [µg/ml] | 50 | n.d. |
| Microsomal stability (human/mouse/rat) [% QH] | <30 | n.d. |
| Plasma protein binding (human) [%] | 97.3 | n.d. |
Structurally related BI-1829 shows much weaker inhibition of human Chymase (IC50 = 850 nM) and therefore is a suitable negative control for in vitro experiments.
BI-1829 which serves as a negative control
BI-1942 was tested in a protease panel (37 proteases) at 10 µM and only hit chymase and cathepsin G (inhibition or stimulation higher than 50%). BI-1942 is more than 100-fold selective against cathepsin G (IC50 = 110 nM)*.
| SELECTIVITY DATA AVILABLE | BI-1942 | BI-1829 |
SafetyScreen44™ with kind support of  | Yes | Yes |
| PDSP5 | Yes | No |
| Invitrogen® | No | No |
| DiscoverX® | No | No |
| Dundee | No | No |
*For detailed assay conditions please refer to Reference 1.
Download selectivity data:
BI-1942_selectivityData.xlsx
BI-1829_selectivityData.xlsx
Co-crystal structure of the Boehringer Ingelheim probe compound and the target protein.
No X-ray co-crystal structure with BI-1942 is available. For a structurally related compound an X-ray structure was solved at Boehringer Ingelheim (see Figure 3).
For reference molecules see Reference 4.
Chymase plays an important and diverse role in the homeostasis for a number of cardiovascular processes and has been linked to heart failure. BI-1942 is a potent inhibitor of human chymase with an IC50 value of 0.4 nM and > 100 fold selectivity against Cathepsin G and is thus a suitable tool for testing biological hypotheses involving human Chymase in vitro.
Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategy
Taylor S. J., Padyana A. K., Abeywardane A., Liang S., Hao M.-H., De Lombaert S., Proudfoot J, Farmer 3rd B. S., Li X., Collins B., Martin L., Albaugh D. R., Hill-Drzewi M., Pullen S. S.,Takahashi H.
J. Med. Chem. 2013, 56, 4465.
Benzimidazolone as potent chymase inhibitor; Modulation of reactive metabolite formation in the hydrophobic (P1) region
Loa H. Y., Nemotoa P. A., Kima J. M., Haoa M.-H., Qiana K. C., Farrowa N. A., Albaughd D. R., Fowlerb D. M., Schneidermanb R. D., Augustc E. M., Martinc L., Hill-Drzewic M., Pullen S. S., Takahashia H., De Lombaerta S.
Bioorg. Med. Chem. Lett. 2011, 21, 4533.
When you plan a publication, please use the following acknowledgement:
BI-1942 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.