NSC45586 sodium 

NSC45586 sodium is an inhibitor of PHLPP. NSC45586 sodium targets the PP2C phosphatase domains of PHLPP1 and PHLPP2, blocks the phosphatase activity of PHLPP, increases the expression level of FOXO1 in the nucleus, and reduces the protein expression of PHLPP1. NSC45586 sodium activates the AKT survival signaling pathway, enhances IGF-1-induced AKT activation, and inhibits the phosphorylation of AKT/ERK under basal conditions. NSC45586 sodium reduces staurosporine-induced neuronal death, preserves notochord cell morphology and KRT19 expression, inhibits cell apoptosis (apoptosis), improves the viability and proliferation of nucleus pulposus cells, upregulates the expression of ACAN/SOX9, and downregulates the expression of MMP13. NSC45586 sodium binds tightly to bovine serum albumin (bovine serum albumin), and exerts a more significant effect on nucleus pulposus in male individuals. NSC45586 sodium can be used in studies related to global cerebral ischemia and intervertebral disc degeneration^[1][2].

PHLPP1/2, Akt^[1]

NSC45586 (0-100 μM; 35 min) sodium activates basal AKT in primary rat cortical neurons and enhances IGF-1-induced AKT activation^[1].
NSC45586 (0-250 μM; 24 h) sodium significantly reduces STS (HY-15141)-induced death of primary rat cortical neurons^[1].
NSC45586 (200 μM; 24 h) sodium increases the number of viable cells in rat primary neuron/astrocyte co-cultures following exposure to STS^[1].
NSC45586 (50 μM; 35 min) sodium significantly inhibits basal AKT and ERK phosphorylation in primary rat astrocytes^[1].
NSC45586 (100 μM; 24 h) sodium reduces the expression of PHLPP1 protein in degenerative human nucleus pulposus (NP) cells, with a more significant effect in male cells^[2].
NSC45586 (0-100 μM; 24 h) sodium exhibits cytocompatibility and significantly promotes the proliferation of degenerated male human nucleus pulposus cells^[2].
NSC45586 (25-100 μM; 24 h) sodium promotes the formation of healthy nucleus pulposus cell phenotypes by upregulating the expression of KRT19, ACAN and SOX9 and downregulating the expression of MMP13 in degenerative human nucleus pulposus cells, and this effect is more pronounced in male cells^[2].
NSC45586 (25-100 μM; 30 min) sodium upregulates the phosphorylation level of AKT and the expression of FOXO1 protein in degenerative human nucleus pulposus cells from male donors in a dose-dependent manner^[2].
NSC45586 (100 μM; 24 h) sodium promotes a healthy nucleus pulposus cell phenotype in degenerative human nucleus pulposus cells from male donors by activating the FOXO1 signaling pathway^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

412.38

C₂₀H₁₇N₆NaO₃

6300-44-3

Solid

Brown to black

O=C(O[Na])C1=CC(/N=N/C2=CC=C(/N=N/C3=CC(C)=C(N)C=C3N)C=C2)=CC=C1O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Jackson TC, et al. Pharmacological inhibition of pleckstrin homology domain leucine-rich repeat protein phosphatase is neuroprotective: differential effects on astrocytes. J Pharmacol Exp Ther. 2013;347(2):516-528.  [Content Brief]

  [2]. Zhang C, et al. Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health. JOR Spine. 2023;7(1):e1306. Published 2023 Dec 4.