ISA-2011B |
Katalog-Nr.GC32691
One-Click Copy Product Info
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ISA-2011B ist ein PIP5K1α-Inhibitor mit vielversprechenden antikarzinogenen Wirkungen.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1395347-24-6
Sample solution is provided at 25 µL, 10mM.
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ISA-2011B, a diketopiperazine fused C-1 indol-3-yl substituted tetra-hydro-isoquinoline, specifically inhibiting the PIP5Kα and the related AKT pathways[1]. ISA-2011B acts as a novel type of anticancer compound that targets PCa cells by targeting AKT/AR-related pathways without toxicity[2].
In vitro, ISA-2011B treatment in primary T cells and Jurkat cells at 25µM for 6h strongly impaired CD3/CD28-mediated induction of PIP5Kα kinase activity and reduced IL-2 mRNA levels, accompanied by cell death[3]. Treatment of C4-2 cells with 50µM ISA-2011B for 48h resulted in a significant down-regulation of cyclin A1, inhibition of cell proliferation and migration, and a decrease in the expression of phosphorylated Ser-473 AKT[4]. Treatment of PC-3 cells with 25µM ISA-2011B for 48 hours resulted in a significant increase in both early and late apoptosis/necrosis[5].
In vivo, ISA-2011B treatment via intraperitoneal injection (40mg/kg; once every other day; i.p.) for 24 days significantly inhibited tumor growth and invasion in the xenograft tumor mouse models[6]. Intraperitoneal injection of ISA-2011B at a dose of 40mg/kg (once every other day) for 15 days suppressed the aggressive growth of AR-V7-overexpressing tumors in xenograft mice, disrupting the PIP5K1α-dependent protein stability of AR-V7[7].
References:
[1] Jin Y, Xue J. Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer[J]. Frontiers in Oncology, 2023, 13: 1323897.
[2] Yin M, Wang Y. The role of PIP5K1A in cancer development and progression[J]. Medical Oncology, 2022, 39(10): 151.
[3] Kunkl M, Porciello N, Mastrogiovanni M, et al. ISA-2011B, a phosphatidylinositol 4-phosphate 5-kinase α inhibitor, impairs CD28-dependent costimulatory and pro-inflammatory signals in human T lymphocytes[J]. Frontiers in Immunology, 2017, 8: 502.
[4] Wang T, Sarwar M, Whitchurch J B, et al. PIP5K1α is required for promoting tumor progression in castration-resistant prostate cancer[J]. Frontiers in cell and developmental biology, 2022, 10: 798590.
[5] Semenas J, Wang T, Sajid Syed Khaja A, et al. Targeted inhibition of ERα signaling and PIP5K1α/Akt pathways in castration‐resistant prostate cancer[J]. Molecular Oncology, 2021, 15(4): 968-986.
[6] Sarwar M, Syed Khaja A S, Aleskandarany M, et al. The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor[J]. Oncogene, 2019, 38(3): 375-389.
[7] Sarwar M, Semenas J, Miftakhova R, et al. Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells[J]. Oncotarget, 2016, 7(39): 63065.
| Cell experiment [1]: | |
Cell lines | C4-2 cells |
Preparation Method | ISA-2011B was dissolved in 0.1% DMSO to a final concentration of 50µM and used to treat C4-2 cells for 48 hours. Briefly, 5×103 viable cells were seeded in 100µl RPMI-1640 medium supplemented with 10% FBS, 1% PSN, and 2mM L-glutamine in a 96-well plate. After 48 hours, 20µl of MTS reagent was added to the medium and incubated for an additional 1 hour in the dark. The absorbance of colored methylene dye products produced by metabolically active living cells was measured at 490nm using a microplate reader. |
Reaction Conditions | 50μM; 48h |
Applications | ISA-2011B significantly inhibited the proliferation of C4-2 cells. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation Method | MDA-MB-231 cells (4×106) were implanted subcutaneously into the female BALB/c nude mice at the age of 8-12 weeks. After the mean tumor volumes reached 50mm3, the mice were randomly assigned into three different groups (6mice/group). The three groups of mice were treated with vehicle (control), docetaxel (10mg/kg) and ISA-2011B (40mg/kg), respectively, by intraperitoneal injection once every other day. The body weight and tumor diameters were measured every other day. The tumor volume was calculated with tumor diameters using the equation (a × b2/2, where a and b represent the larger and smaller diameters, respectively). After the treatment was completed, the mice were sacrificed and the tumors were collected for analysis. |
Dosage form | 40mg/kg; once every other day for 24 days; i.p. |
Applications | ISA-2011B treatment significantly inhibited tumor growth and invasion in the xenograft tumor mouse models. |
References: | |
| Cas No. | 1395347-24-6 | SDF | |
| Canonical SMILES | O=C(N1[C@H](C2=CNC3=C2C=C(Cl)C=C3)C4=C(C=C5C(OCO5)=C4)C[C@]16[H])CN(C)C6=O | ||
| Formula | C22H18ClN3O4 | M.Wt | 423.85 |
| Löslichkeit | DMSO : ≥ 57 mg/mL (134.48 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3593 mL | 11.7966 mL | 23.5933 mL |
| 5 mM | 471.9 μL | 2.3593 mL | 4.7187 mL |
| 10 mM | 235.9 μL | 1.1797 mL | 2.3593 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 4 reference(s) in Google Scholar.)