| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Pan-PHLPP (PHLPP1 and PHLPP2) targeting the PP2C phosphatase domain [1].
Off-target: protein phosphatase 1 (PP1) (approx. 50% inhibition at 100 μM) [1]. Off-target: protein phosphatase 2Cα (PP2Cα) (approx. 50% inhibition at 100 μM) [1]. Off-target: Gβγ subunit (IC50 = 56 μM) [1]. |
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| ln Vitro |
Neutrophil adherence to plated fibrinogen was stimulated by NSC-117079 at 30 μM, increasing it from 9.0±2.4% to 27.0±8.0%. Similarly, 50 ng/mL GM-CSF induced neutrophil cell adhesion to 22.9± 6.0%, increasing it to 47.6±10.9%. Transendothelial migration of neutrophils occurs after neutrophil labeling. According to the findings, PHLPP NSC-117079 by itself can successfully stop Akt from becoming dephosphorylated in neutrophils, but PHLPP's Akt phosphatase can interfere with the migration of neutrophil markers [2].
NSC117079 (35 min treatment) increased basal neuronal AKT phosphorylation (pAKT473) in a dose-dependent manner in primary rat cortical neurons under supplement-starved conditions; did not significantly alter pERK1/2 levels [1]. NSC117079 (50 and 100 μM) blocked IGF-1-induced AKT activation in neurons and altered total AKT levels (Supplemental Fig. 1) [1]. In primary rat astrocytes, NSC117079 (50 μM, 35 min) decreased both basal pAKT473 and pERK1/2 levels [1]. NSC117079 dose-dependently reduced basal viability of primary rat astrocytes after 24 h incubation as measured by CellTiterBlue metabolism; induced a dose-dependent loss of astrocytes and altered cell morphology from large diffuse cell bodies to an elongated shape (Supplemental Fig. 3) [1]. NSC117079 (24 h co-treatment with staurosporine) protected primary rat cortical neurons from staurosporine-induced cell death at lower STS injury levels (50 nM, 100 nM, 200 nM STS); however, a 35-min pretreatment with NSC117079 failed to augment survival compared to injured control [1]. |
| ln Vivo |
In meniscally unstable joints, a single intra-articular injection of Phlpp twin NSC117079 reduces mechanical allodynia and interferes with joint damage. Seven weeks following injury, animals treated with Phlpp twins continued their regular activity levels, whereas three months following joint damage, animals with heart disease moved and walked less. More than 90% of human articular cartilage explants from osteoarthritis patients produce more cartilage extracellular matrix components (glucosamine antioxidants and aggregated proteins) when NSC117079 is added, and in human articular chondrocytes, Phlpp1 substrate increases the phosphorylation of substances (AKT2, ERK1/2, and PKC) [1].
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| Cell Assay |
Cell viability assay (CellTiterBlue): For neurons, cells seeded in 96-well plates at high density (1.5×10^5/well). At DIV10-12, maintenance media replaced with drug treatment media containing different concentrations of staurosporine with or without NSC117079 for 24 h. Then 20 μl CellTiterBlue reagent added, incubated, and color change detected using a plate reader. For astrocytes, cells used at third passage, seeded onto poly-D-lysine coated 96-well plates, grown to confluence, then treated with increasing doses of NSC117079 for 24 h in DMEM/F12/10% FBS, followed by CellTiterBlue reagent incubation for 30-60 min and analysis [1].
Calcein AM live cell staining: For mixed neuron/astrocyte cultures, cells seeded on glass chamber slides, treated with DMSO or 50 nM staurosporine ± 200 μM NSC117079 for 24 h, then washed with DPBS, incubated with 2 μM calcein AM for ~10 min, and live cell images captured under fluorescent microscope. For astrocytes, cells seeded on glass chamber slides, incubated with NSC117079 at indicated concentrations for 24 h, then washed and stained with calcein AM, images captured [1]. Western blot: For neurons, cells grown on 6-well plates, supplement starved 2 h, then treated with increasing doses of NSC117079 for 35 min. Protein extracts harvested in RIPA buffer with EDTA, protease inhibitors, and phosphatase inhibitors. Samples sonicated, centrifuged, protein concentration determined by BCA assay. 20 μg protein per sample loaded onto 7.5% or 4-15% gradient SDS-PAGE gels, run at 200V for 2 h, transferred to PVDF membranes, blocked in 7.5% milk, incubated overnight at 4°C with primary antibodies (pAKT473, AKT total, pERK1/2, ERK1/2 total, GAPDH), then secondary antibodies, developed with ECL-2 Plus detection reagent, films exposed, densitometry analyzed using UN-SCAN-IT software [1]. For astrocytes, cells grown to confluence on 6-well plates, treated with 50 μM NSC117079 for 35 min, then western blot performed similarly [1]. |
| Toxicity/Toxicokinetics |
NSC117079 reduced basal viability of primary rat astrocytes after 24 h incubation, induced dose-dependent loss of astrocytes, and altered cell morphology (elongated shape) [1].
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| References |
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| Additional Infomation |
Inhibits leucine-rich repeat protein phosphatases with a pH domain; structure can be found in the first article.
NSC117079 is a pan-PHLPP inhibitor that targets the PP2C phosphatase domain of PHLPP1 and PHLPP2, thereby activating AKT in neurons but unexpectedly inhibiting AKT/ERK in astrocytes. It has off-target activity against PP1, PP2Cα, and Gβγ. The compound was neuroprotective in cortical neurons when co-treated with staurosporine but not when given as a brief pretreatment. It did not potentiate IGF-1-induced AKT activation; rather, it inhibited it at higher doses. These findings suggest that non-selective PHLPP inhibition may have detrimental effects on astrocytes due to blockade of PHLPP2-mediated pro-survival signaling. The study concludes that selective PHLPP1 inhibitors should be developed for optimal neuroprotection in global brain ischemia [1]. |
| Molecular Formula |
C20H15N3O7S2
|
|---|---|
| Molecular Weight |
473.47900223732
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| Exact Mass |
473.035
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| CAS # |
500363-63-3
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| PubChem CID |
272572
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| Appearance |
Pale purple to purple solid powder
|
| LogP |
2.1
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
32
|
| Complexity |
972
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1=CC(=C2C(C3C=CC=CC=3C(C2=C1N)=O)=O)NC1C=CC=C(C=1)S(N)(=O)=O)(=O)(=O)O
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| InChi Key |
LHSBZAWDPSTOEY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15N3O7S2/c21-18-15(32(28,29)30)9-14(23-10-4-3-5-11(8-10)31(22,26)27)16-17(18)20(25)13-7-2-1-6-12(13)19(16)24/h1-9,23H,21H2,(H2,22,26,27)(H,28,29,30)
|
| Chemical Name |
1-amino-9,10-dioxo-4-(3-sulfamoylanilino)anthracene-2-sulfonic acid
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| Synonyms |
NSC117079; NSC-117079; NSC 117079
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~105.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1120 mL | 10.5601 mL | 21.1202 mL | |
| 5 mM | 0.4224 mL | 2.1120 mL | 4.2240 mL | |
| 10 mM | 0.2112 mL | 1.0560 mL | 2.1120 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 PHLPP inhibitor NSC117079 activates neuronal AKT.J Pharmacol Exp Ther. 2013 Nov;347(2):516-28. |
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 PHLPP inhibitors inactivate AKT/ERK and alter basal viability in astrocytes. PHLPP inhibitors protect cortical neurons from STS injury. |
 PHLPP inhibitor NSC45586 activates neuronal AKT.J Pharmacol Exp Ther. 2013 Nov;347(2):516-28. |
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