| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| 25mg | |||
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| Other Sizes |
| Targets |
SHIP1 (SH2-containing inositol-5'-phosphatase 1)
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|---|---|
| ln Vitro |
AQX-016A (5 μg/mL, 30 minutes) decreases intracellular PIP3 levels via activating 5' phosphatase and prevents the PI3K-mediated increase in PIP3 levels [1]. In a SHIP-dependent way, AQX-01 6A (0–5 μg/mL, 30 minutes) prevents PKB phosphorylation caused by LPS [1]. At 1 and 5 μg/mL doses, AQX-016A (0-5 μg/mL, 2 hours) effectively suppresses TNFa in J774 and peritoneal macrophages [1]. For BMDM, AQX-016A (0–6 μg/mL, 30 minutes) needs SHIP to maximally suppress TNFa production. It also specifically inhibits TNF production in SHIP1+/+ macrophages, but not in SHIP1–/– macrophages [1].. TNFa translation is inhibited by AQX-016A (0–5 μg/mL, 0-90 minutes) [1]. AQX-016A (0–15 μM, 30 minutes) suppresses mast cell and macrophage activation while increasing SHIP1 enzyme activity in intact cells and in vitro [2]. In a manner that is dependent on SHIP, AQX-016A (15 μM, 30 minutes) decreases mast cell and PI3K-dependent macrophage responses while also inhibiting immune cell activation [2].
NSC-741764 is an orally bioavailable SHIP1 agonist. It can activate recombinant SHIP1 enzyme and stimulate SHIP1 activity in vitro. SHIP1 is a lipid phosphatase that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) to phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2), thereby negatively regulating the PI3K/AKT signaling pathway. Activation of SHIP1 leads to inhibition of PI3K signaling, reduced cell proliferation, and decreased production of pro-inflammatory cytokines. NSC-741764 can inhibit the PI3K pathway and TNFα production. |
| ln Vivo |
In a mouse model of endotoxemia, AQX-016A (20 mg/kg, orally, once) significantly reduces plasma TNFa levels and reduces inflammation [1][2].
NSC-741764 (AQX-016A) is an orally bioavailable SHIP1 agonist that can activate recombinant SHIP1 enzyme and stimulate SHIP1 activity in vitro. It can also inhibit the PI3K pathway and TNFα production. The compound induces apoptosis of cancer cell lines in vitro in both a time- and dose-dependent manner. Activation of SHIP1 by NSC-741764 leads to reduced AKT signaling and decreased cell survival in cancer cells. |
| Enzyme Assay |
In vivo studies of NSC-741764 evaluate its efficacy in models of inflammatory diseases and cancer. As an orally bioavailable SHIP1 agonist, the compound can be administered via oral gavage. The compound's ability to inhibit the PI3K pathway and reduce TNFα production makes it a potential therapeutic for a variety of inflammatory diseases. Tumor growth inhibition is assessed in xenograft models.
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| Cell Assay |
Western blot analysis
Cell Types: SHIP1+/+ and SHIP1-/- mast cells [2] Tested Concentrations: 0, 3, 6, 15, 30 μM Incubation Duration: 30 minutes Experimental Results: PIP3-regulated intracellular signaling in SHIP-expressing cells Induction events were inhibited in hematopoietic cells, but not in SHIP-deficient hematopoietic or non-hematopoietic cells. Preferentially inhibits LPS-stimulated PKB phosphorylation in SHIP1+/+ but not SHIP1-/- macrophages in a dose-dependent manner, and inhibits the phosphorylation of PKB, p38MAPK, and extracellular signal-regulated kinase (ERK) in SHIP1+/+ , but not in SHIP1-/- mast cells. SHIP1 enzyme activity is measured using phosphatase assays with recombinant SHIP1 enzyme and appropriate phosphoinositide substrates. Activation of SHIP1 by NSC-741764 is confirmed by measuring increased phosphatase activity. PI3K pathway inhibition is assessed by measuring AKT phosphorylation by Western blot. TNFα production is measured by ELISA in stimulated immune cells. |
| Animal Protocol |
Cellular potency is evaluated in cancer cell lines by measuring apoptosis induction in a time- and dose-dependent manner. PI3K pathway inhibition is assessed by measuring AKT phosphorylation. TNFα production is measured in stimulated immune cells by ELISA. The compound's effects on cell proliferation and survival are assessed using cell viability assays.
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| ADME/Pharmacokinetics |
In vivo efficacy is evaluated in animal models of inflammatory diseases and cancer. NSC-741764 is administered orally as an orally bioavailable compound. Disease severity, inflammatory markers, and tumor growth are assessed. Pharmacodynamic biomarkers including AKT phosphorylation and TNFα levels are measured to confirm target engagement and pathway modulation.
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| Toxicity/Toxicokinetics |
NSC-741764 is an orally bioavailable SHIP1 agonist. The compound demonstrates favorable pharmacokinetic properties that support oral administration in preclinical studies. Detailed PK parameters such as half-life, clearance, and bioavailability are available from preclinical studies.
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| References | |
| Additional Infomation |
Comprehensive toxicological data for NSC-741764 are limited as the compound is primarily used as a research tool. Preclinical studies indicate that the compound is tolerated at efficacious doses. Standard laboratory safety precautions should be observed during handling. The compound is not intended for human therapeutic use.
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| Molecular Formula |
C22H32O2
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|---|---|
| Molecular Weight |
328.488286972046
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| Exact Mass |
328.24
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| Elemental Analysis |
C, 80.44; H, 9.82; O, 9.74
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| CAS # |
849669-54-1
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| PubChem CID |
45028212
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| Appearance |
Light brown to brown solid powder
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| LogP |
6.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
24
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| Complexity |
514
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=CC(=C(C2=C1[C@@]3(CCC4[C@@]([C@H]3C2)(CCCC4(C)C)C)C)O)O
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| InChi Key |
DTFQQAANPRPMBC-CZVICOMLSA-N
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| InChi Code |
InChI=1S/C22H32O2/c1-13-11-15(23)19(24)14-12-17-21(4)9-6-8-20(2,3)16(21)7-10-22(17,5)18(13)14/h11,16-17,23-24H,6-10,12H2,1-5H3/t16?,17-,21+,22-/m1/s1
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| Chemical Name |
(6aR,11aR,11bS)-4,4,6a,7,11b-pentamethyl-1,2,3,4a,5,6,11,11a-octahydrobenzo[a]fluorene-9,10-diol
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| Synonyms |
NSC 741764 NSC-741764 NSC741764AQX 016A AQX-016A AQX016A
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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: ~100 mg/mL (~304.4 mM; with ultrasonication)
Ethanol: ~66 mg/mL (~200.9 mM; with ultrasonication and warming) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (7.61 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.61 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0442 mL | 15.2212 mL | 30.4423 mL | |
| 5 mM | 0.6088 mL | 3.0442 mL | 6.0885 mL | |
| 10 mM | 0.3044 mL | 1.5221 mL | 3.0442 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.
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