SB-3CT is a selective MMP-2 and MMP-9 inhibitor with Ki values of 13.9 and 600 nM, respectively, with much less potency to the other MMPs with Ki values of 206μM, 15μM and 96μM for MMP-1, 3 and 7, respectively[1]. SB-3CT also works as an inhibitor of gelatinase, a member of MMP family. Daily intraperitoneal administration of SB-3CT at dose of 50 mg/kg potently inhibited the liver metastasis and increased survival in an aggressive mouse model of T-cell lymphoma[2]. Treatment with 0.1 or 1μM SB-3CT inhibited capillary-like tubule formation by BMEC-1 cells and the ability of BMEC-1 cells to invade filters coated with Matrigel, but not the cell proliferation up to 10μM. Intraperitoneal injection with SB-3CT at dose of 50 mg/kg potently inhibited intraosseous tumor growth, bone degradation, and intratumoral angiogenesis of human PC3 cells within the marrow of human fetal femur fragments previously implanted in SCID mice[3]. SB-3CT is blood-brain barrier permeable as it can be rapidly absorbed and readily distributed to the brain, and also shows neuroprotective effect[4].
作用机制
SB-3CT directly binds the catalytic zinc ion of MMP-2.[5]
SB-3CT 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human wild type (WT) podocytes and transgenic podocytes
14 mM
48 hours
After MMP-2 inhibition, podocyte apoptosis was attenuated, but NOX4 expression remained almost the same.
Kidney Int Rep. 2023 Jun 19;8(9):1864-1874.
CD8+ T cells
10 mM
6 hours
To assess the effect of SB-3CT on T cell proliferation and cytokine production.
Am J Respir Cell Mol Biol. 2011 May;44(5):700-8.
C6 cells
30 µM
Inhibition of MMP-2/9 can alleviate Pb-induced down-regulation of ZO-1 and occludin.
Int J Biol Sci. 2017 Oct 31;13(11):1351-1360.
SB-3CT 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
CC10-OVA mice
Intratracheal
10 µM
7 days post-administration
To evaluate the effects of SB-3CT on T cell accumulation and lung injury.
Am J Respir Cell Mol Biol. 2011 May;44(5):700-8.
Mice
TMCAO
Intraperitoneal injection
10 mg/kg
3 consecutive days
To specifically inhibit MMP-9-driven pathways in vivo
Mol Ther. 2017 Jun 7;25(6):1448-1459
Mice
Embolic focal cerebral ischemia model
Intraperitoneal injection
25 mg/kg
2 and 4 hours post-ischemia, repeated for seven days
SB-3CT treatment reduced infarct volume and ameliorated neurobehavioral outcomes.
Mol Neurodegener. 2012 May 15;7:21
Mice
Col4a3 C1615Y transgenic mice
Intraperitoneal injection
50 mg/kg
6 days
After MMP-2 inhibition, podocyte apoptosis was attenuated, but NOX4 expression remained almost the same.
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