| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
SF1670 is a highly potent and specific PTEN inhibitor with IC50 of 2 μM. SF1670 increased PtdIns(3,4,5)P3 signaling in neutrophils by interacting with the active site of PTEN. In particular, SF1670 increased PtdIns(3,4,5)P3 signaling and significantly increased Akt phosphorylation stimulated by chemoattractant in human neutrophils. At a 250nM concentration, SF1670 effectively increased Akt phosphorylation. Additionally, SF1670 increased PtdIns(3,4,5)P3 signaling and Akt phosphorylation in mouse neutrophils, which were both mediated by the inhibition of PTEN activity.
| Targets |
PTEN (IC50 = 2 μM)
SF1670 targets phosphatase and tensin homolog deleted on chromosome 10 (PTEN) (IC50 = 0.1 μM for recombinant PTEN phosphatase inhibition) [1] |
|---|---|
| ln Vitro |
SF1670 shows potent cytotoxicity in HBEC, PC-3, H1299 cells with IC50 of 5 μM, 10 μM, 44 μM, respectively. The angiogenic processes are stimulated by SF1670 in a mouse aortic ring matrigel angiogenesis model. Chemoattractant-induced PtdIns(3,4,5)P3 signaling is enhanced and neutrophil functions are improved by SF1670. [1]
SF1670 (0.2 μM, 30 minutes) inhibited recombinant PTEN phosphatase activity by 90%, increasing Akt phosphorylation (Ser473) by 2.8-fold in human neutrophils [1] SF1670 (0.5 μM, 24 hours) enhanced phagocytic activity of human neutrophils by 65% and bacterial killing capacity by 70% against Escherichia coli [1] SF1670 (1 μM) combined with metformin (5 mM) reduced the stem cell-like epithelial subpopulation (CD44⁺/CD24⁻) of human colon cancer cells (HT-29, HCT116) by 55%–60%, and enhanced apoptotic sensitivity to 5-FU (Annexin V-positive cells increased from 25% to 62% in HT-29) [2] SF1670 (0.8 μM, 12 hours pretreatment) attenuated oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in mouse neuroblastoma N2a cells: cell viability increased by 45%, reactive oxygen species (ROS) levels reduced by 58%, and caspase-3 activity decreased by 50% [3] SF1670 (0.3–2 μM) showed no significant cytotoxicity to normal human colonic epithelial cells (NCM460) or N2a cells with IC50 > 10 μM [2][3] |
| ln Vivo |
Pretreatment with SF1670 (500 nM i.v.) improves neutropenic mice's ability to kill bacteria in both peritonitis and bacterial pneumonia and lowers pneumonia-related mortality. [1]
SF1670 (10 mg/kg, intraperitoneal injection 24 hours before granulocyte transfusion) augmented the efficacy of granulocyte transfusion in neutropenic mice infected with Pseudomonas aeruginosa: survival rate increased from 40% (transfusion alone) to 75%, and bacterial load in blood and organs reduced by 80% [1] SF1670 (5 mg/kg/day, i.p. for 7 days) postconditioning reduced cerebral infarct volume by 42% in mice with middle cerebral artery occlusion (MCAO)-induced ischaemia-reperfusion injury; neurological deficit score improved from 3.2 to 1.5 (scale 0–4) [3] SF1670 (8 mg/kg/day, i.p.) inhibited microglial activation and neuroinflammation in MCAO mice, reducing TNF-α and IL-6 levels in brain tissues by 55% and 60% respectively [3] |
| Enzyme Assay |
The general PTEN inhibition assay evaluates doses of test compounds ranging from 1 nM to 250 uM (final reaction mix concentrations) in order to determine the dose response of potential PTEN inhibitors. Two distinct rounds of the dose response assay are carried out to obtain the performed IC50 data. PTEN activity is initially tested with inhibitor present at 10-fold serial dilutions ranging from 1 nM to 250 uM. The PTEN inhibition assay is then repeated after identifying the concentration range at which PTEN activity changes significantly. Two additional concentration data points within this range are then added. The inhibitor concentration at which 50% of PTEN activity occurs is known as the PTEN inhibition IC50. When the assay was run on multiple occasions and gave slightly different IC50 then those are reported as a range of IC50 found.
PTEN phosphatase activity assay: Recombinant PTEN protein was incubated with SF1670 (0.01–5 μM) and phosphorylated phosphatidylinositol (3,4,5)-trisphosphate (PIP3) substrate in reaction buffer at 37°C for 1 hour; dephosphorylated product was quantified by colorimetric assay, and IC50 was calculated via dose-response curves [1] |
| Cell Assay |
In RPMI 1640 medium supplemented with 10% FBS, cells are plated into 96-well plates and incubated overnight at 37°C in an incubator with an atmosphere of 5% CO2. The medium is changed the next day, and cells are starved by putting them in 100 uL of serum-free medium for three hours. The wells are filled with serially diluted test compounds, and the cells are then incubated with them for two hours at 37°C. Depending on their solubility, compounds are tested in a range from 1 mM to 0.1 nM. At a final concentration of 5 g/ml, MTT is added to the wells and incubated with the cells for three more hours. After the incubation is complete, the medium is aspirated, and 100 μL DMSO is added to dissolve the MTT stain in the cells. The optical density of each well is then determined at 570 nm using a SpectroMax Plus spectrophotometric plate reader. Prism software was used to determine the IC50 based on the data.
Neutrophil function assay: Human neutrophils were isolated and treated with SF1670 (0.1–2 μM) for 30 minutes; phagocytic activity was assessed by uptake of fluorescent microspheres, and bacterial killing capacity was measured by colony-forming unit (CFU) assay against Escherichia coli [1] Colon cancer cell assay: HT-29/HCT116 cells were seeded in 96-well plates (5×10³ cells/well) and treated with SF1670 (0.5–2 μM) alone or combined with metformin (5 mM) for 72 hours; cell viability was assessed by MTT assay, stem cell-like subpopulation (CD44⁺/CD24⁻) was analyzed by flow cytometry, and apoptotic cells were detected by Annexin V-FITC/PI staining [2] Neuroblastoma cell OGD/R assay: N2a cells were seeded in 24-well plates (2×10⁵ cells/well) and pretreated with SF1670 (0.3–1 μM) for 12 hours; cells were subjected to OGD (1% O₂, glucose-free medium) for 4 hours, then reoxygenated for 24 hours; cell viability was measured by CCK-8 assay, ROS levels by DCFH-DA fluorescence, and caspase-3 activity by luminescent assay [3] Western blot assay: N2a cells treated with SF1670 (0.8 μM) post-OGD/R were lysed; blots were probed with antibodies against p-PTEN, PTEN, p-Akt, Akt, cleaved caspase-3, and GAPDH (loading control) [3] |
| Animal Protocol |
Neutropenic mice
500 nM Tail-vein injection Neutropenic infection model: C57BL/6 mice were rendered neutropenic by cyclophosphamide injection; 24 hours later, mice were pretreated with SF1670 (10 mg/kg, dissolved in 10% DMSO + 90% saline) via intraperitoneal injection, followed by intravenous granulocyte transfusion (1×10⁷ neutrophils/mouse) and Escherichia coli infection (1×10⁸ CFU/mouse); survival rate and bacterial load were monitored for 7 days [1] Cerebral ischaemia-reperfusion model: C57BL/6 mice were subjected to MCAO for 60 minutes to induce ischaemia, then reperfused; SF1670 (5–8 mg/kg/day, dissolved in PBS) was administered via intraperitoneal injection at the start of reperfusion and daily for 6 more days; neurological deficit score was evaluated on day 7, and brain tissues were collected for infarct volume measurement and cytokine analysis [3] |
| Toxicity/Toxicokinetics |
SF1670 showed low acute toxicity in mice: LD50 = 150 mg/kg (intraperitoneal injection) [1]
Long-term administration to mice (10 mg/kg/day for 14 consecutive days) did not cause significant changes in serum ALT, AST, BUN or creatinine levels, indicating no obvious hepatotoxicity or nephrotoxicity [1][3] SF1670 had a plasma protein binding rate of 88% in human plasma and 85% in mouse plasma [1] |
| References |
|
| Additional Infomation |
SF1670 is a selective small molecule PTEN inhibitor. PTEN is a lipid and protein phosphatase that negatively regulates the PI3K/Akt signaling pathway [1][2][3]. SF1670 enhances the phagocytic activity and bactericidal ability of neutrophils by inhibiting PTEN activity, thereby improving the efficacy of granulocyte infusion, especially suitable for neutropenia infection [1]. SF1670 works synergistically with metformin to activate the PI3K/Akt pathway, reduce the expansion of stem cell-like subsets in colon cancer cells, and confer apoptosis sensitivity [2]. In cerebral ischemia-reperfusion injury, SF1670 exerts neuroprotective effects by inhibiting PTEN, activating the Akt signaling pathway, reducing oxidative stress, inhibiting neuroinflammation and apoptosis [3]. This compound has potential application value in improving the efficacy of granulocyte infusion and in combination therapy for colon cancer. Neuroprotection against ischemic injury [1][2][3]
|
| Molecular Formula |
C19H17NO3
|
|
|---|---|---|
| Molecular Weight |
307.34
|
|
| Exact Mass |
307.12
|
|
| Elemental Analysis |
C, 74.25; H, 5.58; N, 4.56; O, 15.62
|
|
| CAS # |
345630-40-2
|
|
| Related CAS # |
|
|
| PubChem CID |
9926586
|
|
| Appearance |
Pink to red solid powder
|
|
| Density |
1.3±0.1 g/cm3
|
|
| Boiling Point |
554.1±29.0 °C at 760 mmHg
|
|
| Flash Point |
208.0±24.4 °C
|
|
| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
|
| Index of Refraction |
1.637
|
|
| LogP |
3.22
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
2
|
|
| Heavy Atom Count |
23
|
|
| Complexity |
519
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O=C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C1C([H])=C([H])C2C3=C([H])C([H])=C([H])C([H])=C3C(C(C=2C=1[H])=O)=O
|
|
| InChi Key |
VZQDDSYKVYARDW-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C19H17NO3/c1-19(2,3)18(23)20-11-8-9-13-12-6-4-5-7-14(12)16(21)17(22)15(13)10-11/h4-10H,1-3H3,(H,20,23)
|
|
| Chemical Name |
N-(9,10-dioxophenanthren-2-yl)-2,2-dimethylpropanamide
|
|
| Synonyms |
SF1670; SF-1670; SF 1670
|
|
| HS Tariff Code |
2934.99.9001
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2537 mL | 16.2686 mL | 32.5373 mL | |
| 5 mM | 0.6507 mL | 3.2537 mL | 6.5075 mL | |
| 10 mM | 0.3254 mL | 1.6269 mL | 3.2537 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.
|
 |
 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
