260264-93-5
260264-93-5 structure
- Name: GI254023X
- Chemical Name: (2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5-phenylpentanamide
- CAS Number: 260264-93-5
- Molecular Formula: C21H33N3O4
- Molecular Weight: 391.50400
- Catalog: Signaling Pathways Metabolic Enzyme/Protease MMP
- Create Date: 2017-10-14 10:15:07
- Modify Date: 2024-01-06 11:52:46
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GI254023X is a potent MMP9 and ADAM10 inhibitor with IC50s of 2.5 and 5.3 nM, respectively.
| Name | (2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5-phenylpentanamide |
|---|---|
| Synonyms |
BIDD:PXR0042
GI4023 (2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxidanylidene-butan-2-yl]-2-[(1S)-1-[methanoyl(oxidanyl)amino]ethyl]-5-phenyl-pentanamide GI254023X |
| Description | GI254023X is a potent MMP9 and ADAM10 inhibitor with IC50s of 2.5 and 5.3 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
IC50: 2.5 nM (MMP9), 5.3 nM (ADAM10)[1] |
| In Vitro | In cellular assay 25 µM and even a concentration of 1 µM GI254023X strongly reduces constitutive RAGE shedding; also PACAP-inducing shedding of RAGE is significantly reduced. At a concentration of 100 nM, a slight inhibition of RAGE shedding is still observed. In in vitro assays with recombinant proteinases, GI254023X discriminates between ADAM17 (IC50=541 nM) and ADAM10 (IC50=5.3 nM)/MMP9 (IC50=2.5 nM)[1]. CXCL16 shedding is inhibited by ADAM protease inhibitors (e.g GI254023x). A2780 cells are incubated with the ADAM-10/ADAM-17 inhibitor TAPI-2, as well as the ADAM-10-selective inhibitor GI254023x, as the level of expressed ADAM-10 is on average 9.8-fold higher on mRNA level compare with ADAM-17. In addition, GI254023x also prevents CXCL16 shedding from the cell membrane and is even more potent than TAPI-2[2]. When apply the specific ADAM10 (α-secretase) inhibitor GI254023X (5 mM) to serum/glucose-deprived slices, PI counts are significantly increased in comparison with DMSO (carrier)-treated controls[3]. |
| Cell Assay | Cell death is quantified based on plasma membrane permeabilization. When apply the ADAM10 (a-secretase) inhibitor GI254023X (5 mM), slices are cultured in serum-/glucose-free medium for 48 h containing the inhibitor or its respective carrier (DMSO) as control. Round circles of identical size (Ø 500mm) are positioned in equivalent locations within the CA1 region of each hippocampus image and all PI-stained cells are counted using software. Cell viability assays are performed with a commercial kit according to the manufacturer’s instructions. The assay quantitates ATP levels, an indicator of metabolically active cells, photometrically with a fluorescence plate reader. Additionally, the live-dead cell staining kit are applied according to the manual. Cells are simultaneously stained with green fluorescent calcein-AM (4mM; ex/em: 495/515 nm) to detect intracellular esterase activity (viable cells) and red fluorescent ethidium homodimer-3 (2mM; ex/em: 530/635 nm) to indicate loss of plasma membrane integrity (dead cells)[3]. |
| References |
| Molecular Formula | C21H33N3O4 |
|---|---|
| Molecular Weight | 391.50400 |
| Exact Mass | 391.24700 |
| PSA | 105.72000 |
| LogP | 4.45500 |
| Storage condition | -20℃ |
| RIDADR | NONH for all modes of transport |
|---|