Biological Information

Background Information:

Endothelin (ET) is a potent vasoconstrictor that is cleaved from a low-activity precursor, big ET by endothelin converting enzymes (ECE). Two isozymes of ECE (ECE-1 and ECE-2) have been molecularly identified with each shown to belong to the type II membrane-bound metalloprotease family. ECE-1 also cleaves a variety of bioactive peptides such as bradykinin, neurotensin, angiotensin I, and substance P. An ECE-1 inhibitor may be useful for the treatment of heart failure and hypertension.

Family:

Protease

Sub Family:

Neprilysin

Class:

Metallo Peptidase

Protein Name:

ECE1

Uniprot Number:

P42892

Gene Name:

ECE1

Gene ID:

1889

Accession Number:

NM_001397

Organism:

Human

Construct Details:

Fragment (90-770), Recombinant

Assay Information

Assay Type:

Biochemical

Assay Sub Type:

Enzymatic

Functional Mode:

Antagonist

Detection Method:

Spectrofluorimetry

Measured Response:

Fluorescence

Testing Information

Procedure Summary:

Human recombinant ECE-1 expressed in murine myeloma cells NS0 is used. Test compound and/or vehicle is preincubated with 20 ng/ml enzyme‡ in modified MES buffer pH 6.0 for 15 minutes at 25⁰C. The reaction is initiated by addition of 10 μM Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(Dnp) for another 60 minute incubation period. Determination of the amount of Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala formed is read spectrophotometrically at 320 nm/405 nm. Compounds are screened at 10 μM.

Substrate:

10 µM Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(Dnp)

Incubation:

60 min at 25°C

Control Inhibitor:

Phosphoramidon

Criteria For Significance:

≥ 50% of max stimulation or inhibition

Test Concentration / Dose:

Suggested concentration for initial testing is 10 uM

Test Sample Requirements:

Minimum for 1) Screen: 25 μl of 10 mM stock -OR- 1 mg (pre-weighed). 2) Dose Response: 60 μl of 10 mM stock -OR- 1 mg (pre-weighed).

Minimum Order Quantity:

2

Turnaround Time

Standard:

15 Business Days

Reference Compound Data

PubChem ID

46936424

Name

Phosphoramidon

Measurement

0.0020μM -

Clinical Relevance

Therapeutic Area:

Inflammation/Allergy

Additional Information

Brand:

LeadHunter

Testing Location:

Taiwan - Taipei