CatC substrate | BI-1750

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Target protein: 
Cathepsin C
Probe Name: 
BI-1750
MOLECULAR WEIGHT [DA]: 
685.4
In stock: 
16758638

Chemical structure

Highlights

BI-1750 is a novel fluorophore substrate of the protease Cathepsin C (CatC). At 50 µM, BI-1750 is converted by CatC with a Michaelis-Menten kinetic and its highly selective versus the related proteases CatB, CatF, CatH, CatK, CatL and CatS. BI-1750 is well permeable and can be used to monitor intracellular CatC activity in human whole blood assays and other cellular systems. It can also be used to monitor intracellular CatC activity in cells from rats and minipigs.

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Target 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 cells1.

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 neutrophils2.

In vitro Activity

BI-1750 behaves like a substrate for Cathepsin C and all assays proving this behaviour 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” formular.


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

[RFU/30 min]

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

[RFU, n=10]

750 +/- 32

6,449 +/- 171

 

In vitro DMPK and CMC parameters

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.

In vivo DMPK parameters

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.

Selectivity

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

 

BI-1750

Selectivity data available

Cerep®

No

Panlabs®

No

Invitrogen®

No

DiscoverX®

No

Dundee

No

reference molecules

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

Summary

BI-1750 is a stable and highly selective intracellular substrate for the human protease Cathepsin C (CatC).1 It can be used to monitor intracellular CatC activity in ex vivo whole blood assays or other cellular systems. This substrate works in whole blood assays from rats and minipigs as well.

Supplementary data

References

  1. Human Dipeptidylpeptidase I Gene characterization, localization and expression

    Narayanam V. Rao, Gopna V. Rao and John R. Hoidal

    Journal of Biological Chemistry 1997, 272, 10260-10265

  2. Neutrophil Elastase, Proteinase 3, and Cathepsin G as Therapeutic Targets in Human Diseases

    Brice Korkmaz, Marshall S. Horwitz, Dieter E. Jenne and Francis Gauthier

    Pharmcological Review 2010, 62726-759

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