598510

DL-Thiorphan

A thiol containing amido-acid that selectively binds to the active site zinc of metalloproteinases and blocks their activity (IC₅₀ = 2.1 nM for neutral endopeptidase-NEP).

• Synonym(s): DL-Thiorphan, N-[(RS)-2-Benzyl-3-mercaptopropanoyl]-glycine
• Empirical Formula (Hill Notation): C₁₂H₁₅NO₃S
• CAS Number: 76721-89-6
• Molecular Weight: 253.32
• MDL number: MFCD00058435
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• Assay: ≥95% (TLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated; protect from light
• color: white
• solubility: DMSO: 10 mg/mL; ethanol: 10 mg/mL
• shipped in: ambient
• storage temp.: −20°C
• InChI: 1S/C12H15NO3S/c14-11(15)7-13-12(16)10(8-17)6-9-4-2-1-3-5-9/h1-5,10,17H,6-8H2,(H,13,16)(H,14,15)
• InChI key: LJJKNPQAGWVLDQ-UHFFFAOYSA-N

Description

General description

A thiol containing amido-acid that selectively binds to the active site zinc of metalloproteinases and blocks their activity (IC₅₀ = 2.1 nM for neutral endopeptidase-NEP). Although it is shown to inhibit the activity for Aβ peptide degrading enzyme neprilysin in vitro, it has no effect on the secretion of Aβ peptide or amyloid β precursor protein (APP). Also reported to inhibit the activity of angiotensin-converting enzyme (ACE) at much higher concentrations (IC₅₀ = 140 nM); however, it does not affect the activity of endothelin-converting enzyme.

A thiol-containing amido-acid that selectively binds to the active site zinc of neprilysin (also known as neutral endopeptidase and NEP) and inhibits its activity (IC₅₀ = 2.1 nM). Inhibits the β-amyloid (Aβ) degrading activity of neprilysin in vivo, but does not affect the secretion of either Aβ peptide or amyloid precursor protein (APP). Also shown to inhibit other neprilysin-related family members, such as mouse NL1 (IC₅₀ = 47 nM) and the neprilysin homolog from Ascaris suum (IC₅₀ = 22 µM). Inhibits the activity of angiotensin-converting enzyme (ACE) (IC₅₀ = 140 nM), but has no effect on the activity of endothelin-converting enzyme (ECE).

Biochem/physiol Actions

Cell permeable: no

Primary Target
NEP activity

Product does not compete with ATP.

Reversible: no

Target IC₅₀: 2.1 nM for neutral endopeptidase-NEP

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). DMSO stock solutions are stable for up to 2 weeks at -20°C.

Other Notes

Eckman, E.A., et al. 2001. J. Bio. Chem.276, 24540.
Iwata, N., et al. 2001. Science292, 1550.
Shirotani, K., et al. 2001. J. Biol. Chem.276, 21895.
Ghaddar, G., et al. 2000. Biochem. J.347, 419.
Iwata, N., et al. 2000. Nature Med.6, 143.
Takaki, Y., et al. 2000. J. Biochem.128, 897.
Fuller, S.J., et al. 1995. Biochemistry34, 8091.
Sajid, M., et al. 1995. Parasitology.111, 599.
Gomez-Monterrey, I., et al. 1994. J. Med. Chem.37, 1865.
Takahashi, M., et al. 1993. J. Biol. Chem.268, 21394.
Roderick, S.L., et al. 1989. Biochemistry28, 1493.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable