Description: NSC 405020 is a novel, potent noncatalytic small molecule inhibitor of MT1-MMP (Membrane type-1 matrix metalloproteinase), it directly interacts with PEX domain of MT1-MMP and affects PEX homodimerization but has not catalytic activity of MT1-MMP. It specifically targets PEX domain rather than the catalytic domain of MT1-MMP with IC50 >100 μM and does not inhibit the catalytic activity of MT1-MMP or MMP-2. Inhibition of MT1-MMP expression by NSC405020 resulted in decrease of arsenic-mediated invasion of HSC5 cells involving decrease in phosphorylated extracellular signal-regulated kinases (pERK).
References: Cancer Res. 2012 May 1;72(9):2339-49.
Chemical Name: 3,4-Dichloro-N-(1-methylbutyl)benzamide
InChi Key: ARDYECYBETXQFD-UHFFFAOYSA-N
InChi Code: InChI=1S/C12H15Cl2NO/c1-3-4-8(2)15-12(16)9-5-6-10(13)11(14)7-9/h5-8H,3-4H2,1-2H3,(H,15,16)
SMILES Code: O=C(NC(C)CCC)C1=CC=C(Cl)C(Cl)=C1
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
In vitro activity: NSC 405020 is a noncatalytic inhibitor of MT1-MMP, directly interacts with PEX domain of MT1-MMP. NSC 405020 affects PEX homodimerization but not catalytic activity of MT1-MMP. NSC 405020 (100μM) inhibits migration of cells with high level of MT1-MMP, with a reduction of migration efficiency by about 75%. NSC 405020 does not inhibit migration of cells with low level of MT1-MMP and does not inhibit cell adhesion on collagen.
Kinase Assay: Assays are conducted in wells of a 24-well, 8 μm pore size Transwell plate. A 6.5-mm insert membrane is coated with 0.1 mL COL-I (300 μg/mL in MEGM) and then air dried for 16 hours. The collagen coating is rehydrated for 1 hour in 0.2 mL MEGM. The inner chamber contains MEGM-10% FBS as a chemoattractant. The compounds (10–100 μmol/L) or DMSO (0.1%–1%) are added to both inner and outer chambers. Before plating in the outer chamber, cells (5×104) are coincubated for 20 minutes with the compounds or DMSO in MEGM. Cells are allowed to migrate for 16 to 18 hours. The cells remaining on the top surface of the membrane are removed with a cotton swab. The cells on the bottom surface of the membrane are fixed and stained (0.2% crystal violet). The incorporated dye is extracted with 1% SDS and the A570 is measured.
Cell Assay: Assays are conducted in wells of a 96-well flat bottom, white wall plates. 184B5-MT and MCF7-β3/MT cells (5×104) are grown for 16 hours in MEGM-10% FBS and DMEM-10% FBS, respectively. 184B5-MT cells are replenished with fresh MEGM (0.1 mL per well) and incubated for an additional 24 hours in the presence of the compounds (100 μM) or vehicle (1% DMSO). MCF7-β3/MT cells are replenished with fresh DMEM-10% FBS (0.1 mL per well) and incubated for an additional 6 hours in the presence of the compounds (400 μM) or vehicle (2% DMSO). The viable cells are counted using a luminescent ATP-Lite assay.
Cancer Res. 2012 May 1;72(9):2339-49.
Purity ≥98%