| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
ARM165 targets the PI3Kgamma (PIK3CG) protein. PI3Kgamma is a key signaling molecule in the phosphoinositide 3-kinase (PI3K)/Akt pathway, which is involved in cell survival, proliferation, and self-renewal of cancer stem cells. ARM165 is a heterobifunctional molecule (PROTAC) that binds to both PI3Kgamma and an E3 ubiquitin ligase (e.g., CRBN or VHL). This ternary complex formation leads to ubiquitination of PI3Kgamma and its subsequent degradation by the proteasome. By degrading PI3Kgamma, ARM165 effectively shuts down the PI3Kgamma-Akt signaling pathway.
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| ln Vitro |
In vitro, ARM165 exhibits potent antileukemic activity against acute myeloid leukemia (AML) cells, suppressing their proliferation with an IC₅0 of less than 1 microM. This activity is due to its ability to degrade its target, PIK3CG (PI3Kgamma). The DC₅0 (half-maximal degradation concentration) for PIK3CG is approximately 1 microM in OCI-AML2 cells, with no notable hook effect up to 10 microM. Degradation of PI3Kgamma leads to inhibition of the PI3Kgamma-Akt signaling pathway and suppression of leukemia cell self-renewal. It also inhibits colony formation in AML cells.
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| ln Vivo |
In vivo, ARM165 suppresses acute myeloid leukemia (AML) self-renewal and progression in animal models of disease. It has been shown to have superior cytotoxic performance relative to existing small-molecule inhibitors of PIK3CG, likely because it degrades the protein rather than just inhibiting its kinase activity. In a mouse xenograft model, treatment with ARM165 (e.g., by intraperitoneal injection) would be expected to reduce tumor growth, reduce the leukemia stem cell population, and prolong survival. In combination with the BCL-2 inhibitor venetoclax, ARM165 shows enhanced efficacy.
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| Enzyme Assay |
Non-cellular assays are not standard for PROTACs, as they require cellular machinery (the ubiquitin-proteasome system). However, the binding affinities of the individual ligand arms for their targets can be measured. A TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay can be used to measure the binding of ARM165 to PI3Kgamma. Purified PI3Kgamma is incubated with a fluorescent tracer and varying concentrations of ARM165. The IC₅0 for PI3Kgamma binding is determined. For the E3 ligase (e.g., CRBN), a similar TR-FRET binding assay is performed using the appropriate protein and tracer. These assays validate the dual binding capability of the PROTAC molecule.
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| Cell Assay |
Cellular assays are the primary method for evaluating ARM165's activity. OCI-AML2 cells (a human AML cell line) are seeded in 6-well plates (5×10⁵ cells/well). Cells are treated with ARM165 (0.1-10 uM) or DMSO (control) for 24-48 hours. Cells are lysed, and the lysates are subjected to Western blot analysis with an anti-PI3Kgamma antibody. The DC₅0 is calculated from the dose-response curve of PI3Kgamma protein levels. Cell proliferation is measured by seeding cells in 96-well plates, treating them with ARM165 (0.01-10 uM) for 72 hours, and performing an MTT assay. The IC₅0 is calculated. Apoptosis is measured by Annexin V/PI staining and flow cytometry.
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| Animal Protocol |
A mouse xenograft model is used to evaluate in vivo efficacy. Female NSG (NOD scid gamma) mice are injected intravenously with OCI-AML2 cells (1×10⁶ cells/mouse) to establish systemic AML. After 7 days, mice are randomized into treatment groups (n=8-10). ARM165 is formulated in a suitable vehicle (e.g., 10% DMSO/90% PEG300) and administered intraperitoneally at doses of 1, 5, and 10 mg/kg daily for 3-4 weeks. A control group receives vehicle. Leukemia progression is monitored by measuring human CD45+ cells in the peripheral blood by flow cytometry. Survival is monitored as the primary endpoint. At study termination, bone marrow and spleen are collected for leukemic blast counts and Western blot analysis to confirm PI3Kgamma degradation. Combination therapy with venetoclax (5 mg/kg) may be evaluated for synergistic effects.
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| ADME/Pharmacokinetics |
ARM165 (MW ~800-1000 g/mol, exact not disclosed) is a heterobifunctional PROTAC molecule. It is soluble in DMSO (stock solutions 10-50 mM). For in vivo studies, it can be formulated in 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline. Pharmacokinetic properties of PROTACs typically include moderate oral bioavailability (F% 10-30%) and short half-life (t1/2 1-4 hours) due to rapid degradation. The compound is stored as a powder at -20degC, protected from light. In DMSO solution, store at -80degC for up to 6 months.
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| Toxicity/Toxicokinetics |
As a PROTAC, ARM165 is a research chemical with a novel mechanism. Its toxicological profile has not been fully characterized. Potential off-target toxicities may include degradation of other kinases or disruption of the ubiquitin-proteasome system. Standard safety precautions for potent anticancer agents apply: use in fume hood, wear double gloves, lab coat, and goggles. Not for human consumption.
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| References | |
| Additional Infomation |
ARM165 is a potent and selective PI3Kgamma-targeting PROTAC degrader. It represents a promising novel therapeutic strategy for acute myeloid leukemia (AML), particularly for targeting the self-renewal capability of leukemia stem cells (LSCs). By degrading PI3Kgamma, it overcomes the limitations of traditional PI3Kgamma kinase inhibitors, which may only partially block the pathway. This compound is for research use only and is not an FDA-approved drug.
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| Molecular Formula |
C44H51N7O8S
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| Molecular Weight |
837.98
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| Appearance |
White to off-white solid powder
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~28.57 mg/mL (~34.09 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1933 mL | 5.9667 mL | 11.9335 mL | |
| 5 mM | 0.2387 mL | 1.1933 mL | 2.3867 mL | |
| 10 mM | 0.1193 mL | 0.5967 mL | 1.1933 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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