CatC substrate
BI-1750
BI-1750 is a novel fluorophore substrate for the human protease Cathepsin C (CatC), which enzymatically cleaves BI-1750 with a Michaelis-Menten kinetic. It is stable and highly selective, with no conversion by the related enzymes CatB, CatF, CatH, CatK, CatL and CatS observed. BI-1750 is cell permeable and may be used to monitor intracellular CatC activity in ex vivo human whole blood assays and other cellular systems, including activity in cells from rodents.
More information
Cathepsin C (CatC) is a lysosomal cysteine protease. It is expressed at high levels in lung, kidney, and placenta and at moderate to low levels in many other organs. Among immune/inflammatory cells, the mRNA is expressed at high levels in polymorphonuclear leukocytes and alveolar macrophages and their precursor cells.1
In the bone marrow, CatC activates neutrophil serine proteases (NSPs) during myelopoiesis of neutrophils. Inhibition of CatC leads to a decrease in neutrophil elastase (NE), cathepsin G (CG), proteinase 3 (PR3) and NSP4 activities in circulating neutrophils.2
BI-1750 behaves like a substrate for Cathepsin C and all assays proving this behavior are given below with different assay conditions.
| Probe name | BI-1750 |
| MW [Da] | 685.43 |
| CatC (IC50) [nM]a | 120,000 |
a Assay conditions for CatC assay are available in the patent WO2014140075. More detailed experimental conditions can always be obtained via the “Contact us” form.
At 50 µM, BI-1750 is enzymatically cleaved by CatC similar to the standard substrate Gly-Arg-AMC:
| Substrate | Vmax [RFU/sec] |
| 50 µM Gly-Arg-AMC | 29 |
| 50 µM BI-1750 | 22 |
BI-1750 is converted by isolated primary human neutrophils (PMN) depending on cell-number:
| PMN (*1e5) | Substrate turnover |
| 19.4 | 5,045 |
| 9.7 | 2,763 |
| 4.85 | 1,526 |
| 2.43 | 769 |
| 1.21 | 408 |
| 0.61 | 179 |
| 0.3 | 69 |
Turnover of BI-1750 in human whole blood: (40 µM BI-1750, 30 min incubation at 37oC)
| Plasma control [RFU, n=10] | Whole blood |
| 750 +/- 32 | 6,449 +/- 171 |
No data available, this tool can be used to monitor intracellular CatC activity in human whole blood assays and other cellular systems but in in vivo assays.
No data available, this tool can be used to monitor intracellular CatC activity in human whole blood assays and other cellular systems but in in vivo assays.
BI-1750 is not converted by the related enzymes CatB, CatF, CatH, CatK, CatL and CatS.
| Enzyme | Enzyme specific substrate | BI-1750 | |
Substrate | Turnover [RFU/min] | Turnover [RFU/min] | |
| CatB | Z-Arg-Arg-AMC | 80 | 0 |
| CatF | Z-Leu-Arg-AMC | 26 | 0 |
| CatH | H-Arg-AMC | 86 | 0 |
| CatL | Z-Phe-Arg-AMC | 114 | 0 |
| CatK | Z-GPR-AMC | 36 | 0 |
| CatS | Z-Val-Val-Arg-AMC | 69 | 0.1 |
| SELECTIVITY DATA AVILABLE | BI-1750 |
SafetyScreen44™ with kind support of  | Yes |
| Invitrogen® | No |
| DiscoverX® | No |
| Dundee | No |
Download selectivity data:
BI-1750_selectivityData.xlsx
Daniel Guay, Christian Beaulieu and David M. Percival Therapeutic Utility and Medicinal Chemistry of Cathepsin C Inhibitors Current Topics in Medicinal Chemistry 2010, 10, 2010, 708-716 DOI: 10.2174/156802610791113469, PubMed
BI-1750 is a stable and highly selective intracellular substrate for the human protease Cathepsin C (CatC).
2 D structure formats available
Cathepsin C Substrate | BI-1750.png
When you plan a publication, please use the following acknowledgement:
BI-1750 was kindly provided by Boehringer Ingelheim via its open innovation platform opnMe, available at https://www.opnme.com.