| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
ISA-2011B targets phosphatidylinositol-4-phosphate 5-kinase-α (PIP5Kα), an enzyme that synthesizes phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is a key lipid signaling molecule that regulates various cellular processes, including cell proliferation, survival, and migration. Overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with elevated levels of the androgen receptor.
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| ln Vitro |
Compared with the vehicle-treated control, the proliferation rates of PC-3 cells were considerably reduced to 58.77%, 48.65%, and 21.62%, respectively, after treatment with 10, 20, and 50 μM ISA-2011B. ISA-2011B has the highest binding affinity for PIP5K1α and MAP/microtubule affinity-regulated kinases 1 and 4 (MARK1 and MARK4) among 460 kinases. ISA-2011B treatment suppressed 78.6% of PIP5K1α expression in PC-3 cells [1]. ISA-2011B induced a considerable decrease of AR-V7 and CDK1 in the nucleus and cytoplasm of 22Rv1 cells. ISA-2011B therapy also reduces AR expression in the nucleus without diminishing cytoplasmic AR[2].
In vitro, ISA-2011B inhibits PIP5Kα activity. It exhibits anti-proliferative activity and induces apoptosis in prostate cancer cells. It effectively reduces the growth of tumor cells by inhibiting the PI3K/AKT and its downstream survival, proliferation, and invasion pathways. |
| ln Vivo |
ISA-2011B effectively reduces the growth of tumor cells in xenograft mice and is mediated by inhibiting PIP5K1α-related PI3K/AKT and its downstream survival, proliferation and invasion pathways [1]. Overexpression of AR-V7 raises PIP5K1α and promotes rapid PCa growth in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B decreases the growth and invasiveness of xenograft tumors overexpressing AR-V7. ISA-2011B inhibits the PIP5K1α-dependent protein stability of AR-V7, consequently decreasing the invasive growth of AR-V7-high tumors in xenograft mice [2].
In vivo, ISA-2011B reduces the growth of tumor cells in xenograft mice. Its ability to inhibit PIP5Kα and downstream signaling pathways makes it a promising candidate for the treatment of prostate cancer and other malignancies where PIP5Kα is overexpressed. |
| Enzyme Assay |
PIP5Kα inhibition is assessed using biochemical assays with purified recombinant enzyme. The enzyme is incubated with its substrate, phosphatidylinositol-4-phosphate, and varying concentrations of ISA-2011B. The production of PIP2 is measured to determine the compound's inhibitory potency.
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| Cell Assay |
Antiproliferative activity is evaluated in prostate cancer cell lines. Cells are treated with ISA-2011B, and cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is detected by Annexin V staining or caspase activity assays.
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| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models of prostate cancer. ISA-2011B is administered orally or intraperitoneally, and tumor volume is measured over time. Tumor growth inhibition and markers of apoptosis and proliferation are assessed.
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| ADME/Pharmacokinetics |
As a small molecule, ISA-2011B is expected to have favorable drug-like properties, including oral bioavailability. It is soluble in DMSO at 85 mg/mL. Its pharmacokinetic profile is consistent with a small molecule kinase inhibitor.
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| Toxicity/Toxicokinetics |
As a PIP5Kα inhibitor, potential toxicities may include effects on normal cells that rely on PIP2 signaling for survival and proliferation. However, its selectivity for PIP5Kα over other kinases may reduce off-target effects.
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| References |
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| Additional Infomation |
Antitumor drugs; first-source structures
ISA-2011B is a research compound used to study the role of PIP5Kα in cancer and to validate it as a therapeutic target. It is especially valuable in models of solid tumors and hematologic malignancies where PIP5Kα is overexpressed. Its ability to inhibit the PI3K/AKT pathway makes it a promising candidate for combination therapy with other targeted agents. |
| Molecular Formula |
C22H18CLN3O4
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|---|---|
| Molecular Weight |
423.85
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| Exact Mass |
423.098
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| CAS # |
1395347-24-6
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| PubChem CID |
49853637
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| Appearance |
White to off-white solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
714.9±60.0 °C at 760 mmHg
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| Flash Point |
386.1±32.9 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.762
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| LogP |
2.23
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
30
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| Complexity |
737
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1CC(=O)N2[C@H](C1=O)CC3=CC4=C(C=C3[C@H]2C5=CNC6=C5C=C(C=C6)Cl)OCO4
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| InChi Key |
FSEZESVJDPKRDS-UWJYYQICSA-N
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| InChi Code |
InChI=1S/C22H18ClN3O4/c1-25-9-20(27)26-17(22(25)28)4-11-5-18-19(30-10-29-18)7-13(11)21(26)15-8-24-16-3-2-12(23)6-14(15)16/h2-3,5-8,17,21,24H,4,9-10H2,1H3/t17-,21-/m0/s1
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| Chemical Name |
(2S,8S)-2-(5-chloro-1H-indol-3-yl)-6-methyl-13,15-dioxa-3,6-diazatetracyclo[8.7.0.03,8.012,16]heptadeca-1(17),10,12(16)-triene-4,7-dione
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| Synonyms |
ISA-2011B ISA 2011B ISA2011B
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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 (~235.93 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 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 (5.90 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 4 mg/mL (9.44 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3593 mL | 11.7966 mL | 23.5933 mL | |
| 5 mM | 0.4719 mL | 2.3593 mL | 4.7187 mL | |
| 10 mM | 0.2359 mL | 1.1797 mL | 2.3593 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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