Uses
Competitive, mechanism-based inhibitor of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). It possesses Ki values in the nanomolar range against the gelatinases (14nM for MMP-2; 600nM for MMP-9), but in the micromolar range against other metalloproteinases (206μM for MMP-1, 15μM for MMP-3, 96μM for MMP-7, and 4μM for ADAM17/TACE). This inhibitor has also been used in vitro, in vivo, and in tissue culture. In vivo, it is metabolized to an even more potent gelatinase inhibitor.
Definition
ChEBI: 2-[(4-phenoxyphenyl)sulfonylmethyl]thiirane is an aromatic ether.
Biochem/physiol Actions
SB-3CT is a potent matrix metalloproteinase MMP-2 and MMP-9 inhibitor. Matrix metalloproteinases (MMPs) are involved in a number of activities including angiogenesis and embryogenesis. In particular, gelatinases A (MMP-2) and B (MMP-9), are thought to facilitate tumor metastasis. SB-3CT exhibits a covalent mechanism based behavior in inhibition of MMP-2 and MMP-9. This inhibitor appears to have similarity to TIMP-1 and TIMP-2 in the slow-binding component of inhibition. SB-3CT has been shown to directly bind to the zinc in the catalytic site of MMP-2. SB-3CT does not affect the activities of MMP-1 (Ki = 206 μM) MMP-3 (Ki = 15 μM), or MMP-7 (Ki = 96 μM).
Enzyme inhibitor
This thiirane (FW = 306.41 g/mol), also known as matrix
metalloproteinase-2/matrix metalloproteinase-9 inhibitor IV (MMP-
2/MMP-9 inhibitor IV) and SB-3CT, is a mechanism-based inhibitor of
gelatinase A, or matrux metalloproteinase 2, Ki = 0.014 μM, gelatinase
B, or matrix metalloproteinase 9, Ki = 0.6 μM, membrane-type matrix
metalloproteinase 1, matrix metalloproteinase 14, matrilysin, Ki = 96
μM, stromelysin 1, or matrix metalloproteinase 3, Ki = 15 μM.
in vivo
SB-3CT (i.p.; 50 mg/kg; every other day; five weeks) inhibits intraosseous growth of human PC3 cells within the marrow of human fetal femur fragments previously implanted in SCID mice[3].
| Animal Model: | Five-week-old male C.B.-17.SCID mice[3] |
| Dosage: | 50 mg/kg |
| Administration: | IP; every other day; five weeks |
| Result: | Inhibited intraosseous growth of human PC3 cells within the marrow of human fetal femur fragments previously implanted in SCID mice.
|
IC 50
MMP-2: 13.9 nM (Ki); MMP-9: 600 nM (Ki)
