| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
AK-2292 targets the transcription factors STAT5A and STAT5B. As a PROTAC, it is a bifunctional molecule that binds to the target protein (STAT5) and an E3 ubiquitin ligase, bringing them into close proximity. This leads to the ubiquitination and subsequent degradation of STAT5A/B by the proteasome. This mechanism of action results in the selective inhibition of STAT5 activity.
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| ln Vitro |
The proliferation of SKNO1, MV4;11, and Kasumi-3 cells is inhibited by AK-2292 (0.0015-15 μM; 4 days) with IC50 values of 0.36, 0.35, and 0.18 μM, respectively [1]. In the SKNO1 cell line, AK-2292 (0.008-5 μM; 18 h) lowers the amounts of STAT5A, STAT5B, and pSTAT5Y694 proteins [1]. In the MV4;11 acute leukemia cell line, AK-2292 (0.008-5 μM; 6 h) efficiently lowers the levels of STAT5 and pSTAT5Y694 [1].
In vitro, AK-2292 is a highly potent and selective STAT5 degrader. It induces degradation of STAT5A/B proteins with a DC50 of 0.10 µM. It shows outstanding selectivity for STAT5 over all other STAT proteins (STAT1-4, STAT6) and over 6,000 non-STAT proteins. It inhibits the cell growth of AML cell lines SKNO1, MV4;11, and Kasumi-3, with IC50s of 0.36, 0.35, and 0.18 µM, respectively. |
| ln Vivo |
In a mouse MV4;11 xenograft model, AK-2292 (50-200 mg/kg; ip once daily, 5 days a week for 3 weeks) suppresses tumor growth [1]. In mouse MV4;11 xenograft tissue, AK-2292 (150 mg/kg; a single ip) causes >95% fast depletion of STAT5 and pSTAT5Y694 proteins [1]. With a plasma half-life of 1.9 hours, moderate clearance (CL=0.77 L/h/kg), and acceptable volume distribution (Vz=2.1 L/kg), AK-2292 (ip) demonstrates good plasma exposure [1].
In vivo, AK-2292 induces STAT5 depletion in normal mouse tissues and in human chronic myeloid leukemia (CML) xenograft tissues. It achieves tumor regression in AML and CML xenograft mouse models. These findings demonstrate its potential as a therapeutic agent for STAT5-driven leukemias. |
| Enzyme Assay |
The degradation activity of AK-2292 is assessed using cellular assays. Cells are treated with varying concentrations of the compound, and the levels of STAT5A and STAT5B proteins are measured by Western blot. The DC50, the concentration required for 50% degradation, is calculated from the dose-response curve. The selectivity of degradation is confirmed by assessing the levels of other proteins.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: SKNO1 cells Tested Concentrations: 0.008, 0.04, 0.2, 1, 5 μM Incubation Duration: 18 hrs (hours) Experimental Results: decreased the levels of STAT5A, STAT5B, and pSTAT5Y694 by >75% at 0.2 μM and by > 95% at 1 μM. Has no obvious effect on the levels of STAT1, STAT2, STAT3, STAT4, and STAT6 proteins at concentrations up to 5 μM. Cell Viability Assay[1] Cell Types: SKNO1, MV4;11, and Kasumi- 3 cells Tested Concentrations: 0.0015, 0.015, 0.15, 1.5, 15 μM Incubation Duration: 4 days Experimental Results: Effectively inhibited cell growth with IC50s of 0.36, 0.18, and 0.35 μM, respectively. The cellular activity of AK-2292 is evaluated in various leukemia cell lines. Cells are treated with AK-2292, and its effect on cell viability and proliferation is measured. The reduction in STAT5 protein levels is confirmed by Western blot. The compound's effect on downstream STAT5 target genes can also be assessed. |
| Animal Protocol |
Animal/Disease Models: SCID (severe combined immunodeficient) mouse bearing MV4;11 tumors[1]
Doses: 50, 100, 200 mg/kg Route of Administration: IP injection, one time/day, 5 days per week for 3 weeks Experimental Results: Inhibited tumor growth in a dose-dependent manner and achieved 50, 60, and 80% of tumor growth inhibition at doses of 50, 100, and 200 mg/kg, respectively. Did not induce animal weight loss or any other signs of toxicity. In animal studies, AK-2292 is administered to mice bearing AML or CML xenografts. The route of administration and dosing regimen are determined based on its pharmacokinetic properties. Tumor growth inhibition is measured, and at study termination, tumors are harvested for analysis of STAT5 degradation and other pharmacodynamic markers. |
| ADME/Pharmacokinetics |
AK-2292 is a PROTAC molecule with a molecular weight of 1070.13 and a formula of C52H56F2N7O10P. It is soluble in DMSO (125 mg/mL) and is typically stored at 4°C or -80°C in solution. It contains an alkyne group, making it a click chemistry reagent. Detailed pharmacokinetic parameters are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicology data for AK-2292 is not publicly available in detail. As a research compound, its safety profile is under investigation. Its use is limited to research applications and it is not intended for human therapeutic use without further development.
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| References | |
| Additional Infomation |
AK-2292 (CAS: 2984506-77-4) is a highly selective and potent STAT5 degrader that represents a novel approach to targeting this transcription factor. Its ability to induce tumor regression in preclinical models of leukemia highlights its therapeutic potential. It is a key tool for studying STAT5 biology and for validating STAT5 as a therapeutic target in hematological malignancies.
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| Molecular Formula |
C52H54F2N7O10PS2
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| Molecular Weight |
1070.13
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| CAS # |
2984506-77-4
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| Appearance |
Off-white to light yellow 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 0.9345 mL | 4.6723 mL | 9.3447 mL | |
| 5 mM | 0.1869 mL | 0.9345 mL | 1.8689 mL | |
| 10 mM | 0.0934 mL | 0.4672 mL | 0.9345 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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