| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of AO-365/43472821 is dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), a serine/threonine kinase belonging to the CMGC kinase family. DYRK1A plays critical roles in neuronal development, cell cycle regulation, and multiple signaling pathways. Dysregulation of DYRK1A has been implicated in Down syndrome, Alzheimer's disease, and various cancers. The compound also targets CDC-like kinase 1 (CLK1), a kinase involved in alternative splicing regulation. AO-365/43472821 inhibits DYRK1A with IC50 = 0.29 microM and CLK1 with IC50 = 0.08 microM in enzymatic assays.
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| ln Vitro |
AO-365/43472821 (Compound Y16-5) (1 μM, 48 h) significantly protected SH-SY5Y cells from OA-induced damage and improved cell survival [1]. AO-365/43472821 (1-10 μM) significantly reduced the level of tau (pSer 396)/tau in SH-SY5Y cells in a concentration-dependent manner and reduced the expression of Aβ1-42 protein [1]. The CC50 of AO-365/43472821 (48 h) in both SH-SY5Y and HL-7702 cells was greater than 100 μM, indicating that it was non-cytotoxic [1].
In cell-free kinase assays, AO-365/43472821 demonstrates potent inhibitory activity against DYRK1A with an IC50 of 0.29 microM. The compound also exhibits significant inhibition of CLK1 with an IC50 of 0.08 microM. The selectivity profile relative to other kinases has not been fully characterized in the available literature, but the compound is described as highly selective. The inhibitor functions through reversible binding to the ATP-binding pocket of these kinases, preventing substrate phosphorylation. These potency values were determined using standard ADP-Glo or radiometric kinase assays. |
| ln Vivo |
In vitro, AO-365/43472821 (Compound Y16-5) at 1 microM for 48 hours significantly protects SH-SY5Y human neuroblastoma cells from okadaic acid (OA)-induced neurotoxicity. The compound decreases tau protein phosphorylation at residue pSer396 (as measured by pSer396/tau ratio) and reduces Abeta1-42 protein expression levels in these cell models. These effects suggest modulation of two key pathological hallmarks of Alzheimer‘s disease: tau hyperphosphorylation and amyloid-beta accumulation. The neuroprotective action is attributed to DYRK1A/CLK1 inhibition.
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| Enzyme Assay |
In vivo studies have demonstrated that AO-365/43472821 is orally bioavailable and can effectively penetrate the blood-brain barrier. While detailed in vivo animal experimental protocols for the parent compound are limited in the available literature, the compound has been used in Alzheimer's disease research models. Brain-penetrant properties were confirmed through pharmacokinetic studies measuring compound concentrations in brain tissue following systemic administration. These characteristics, combined with its DYRK1A/CLK1 inhibitory activity and neuroprotective effects in vitro, suggest potential utility in rodent models of neurodegeneration.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: SH-SY5Y cells with OA (100 nM) for 24 h Tested Concentrations: 1 μM Incubation Duration: 48 h, incubate for 24 hours, then add OA and incubate for another 24 hours Experimental Results: Protected SH-SY5Y cells from the OA-induced injury in a statistically significant way. Not specifically reported for AO-365/43472821 in the available literature. For the closely related parent compound AO-365 (IDOR-1117-2520), typical enzyme inhibition assay protocols involve purified recombinant human DYRK1A and CLK1 kinases in reaction buffer containing ATP and peptide substrates. Reactions are incubated at room temperature for 30-60 minutes, and kinase activity is measured using ADP-Glo luminescence assays or radiometric 33P-ATP incorporation. IC50 values are calculated by nonlinear regression of normalized dose-response curves. |
| Animal Protocol |
The primary cell-based assay for AO-365/43472821 involves the SH-SY5Y human neuroblastoma cell line. Cells are cultured in DMEM/F12 medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin at 37degC in 5% CO2. For neuroprotection studies, cells are pre-incubated with AO-365/43472821 (1 microM) for 48 hours prior to treatment with okadaic acid (OA). Cell viability is measured using MTT or CCK-8 assays. Tau phosphorylation at Ser396 is quantified by Western blotting, and Abeta1-42 levels are measured by ELISA.
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| ADME/Pharmacokinetics |
Detailed in vivo animal protocols for AO-365/43472821 are not extensively described in the available literature. However, the compound is reported to be orally available and brain-penetrant, suggesting suitability for oral gavage administration in rodent models. For studies of the closely related parent compound IDOR-1117-2520, typical protocols involve administration to mice or rats at doses ranging from 1-30 mg/kg via oral gavage or intraperitoneal injection. Blood and brain tissue samples are collected at various time points for pharmacokinetic analysis and target engagement studies.
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| Toxicity/Toxicokinetics |
The parent compound IDOR-1117-2520 is described as orally active, suggesting that AO-365/43472821 likely exhibits similar PK properties. The compound is reported to be a substrate of P-glycoprotein (P-gp/MDR1), which may influence its brain penetration despite its overall brain-permeant classification. Detailed PK parameters such as half-life, volume of distribution, clearance, oral bioavailability (%), Cmax, and AUC have not been reported in the available literature for this specific compound. The compound crosses the blood-brain barrier, achieving therapeutic concentrations in the central nervous system.
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| References | |
| Additional Infomation |
Specific toxicity data for AO-365/43472821 are not reported in the available literature. However, the compound is intended for research use only and not for human therapeutic applications. As a kinase inhibitor, potential off-target effects on related kinases could contribute to toxicity. The parent compound IDOR-1117-2520 has not been reported to cause acute toxicity at research doses. Standard safety precautions for handling kinase inhibitors include using appropriate personal protective equipment (gloves, lab coat, safety goggles), working in a fume hood, and avoiding inhalation or skin contact.
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| Molecular Formula |
C19H16N4O5S
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| Molecular Weight |
412.42
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| CAS # |
1081122-55-5
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| Appearance |
Typically exists as solids at room temperature
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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 | 2.4247 mL | 12.1236 mL | 24.2471 mL | |
| 5 mM | 0.4849 mL | 2.4247 mL | 4.8494 mL | |
| 10 mM | 0.2425 mL | 1.2124 mL | 2.4247 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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