| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The target of this compound is CaMKIIdelta, a serine/threonine-protein kinase that is a key mediator of calcium signaling in the heart and brain. It binds to the ATP-binding pocket of the kinase domain, inhibiting its autophosphorylation and subsequent activation. CaMKIIdelta is a validated drug target for preventing ischemic injury, cardiac hypertrophy, and arrhythmias (e.g., atrial fibrillation).
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| ln Vitro |
In vitro, CaMKIIdelta-IN-1 hydrochloride shows potent enzymatic inhibition with an IC50 value of 12 nM for CaMKIIdelta. It is selective against other CaMKII isoforms and related kinases. In cell-based assays, it inhibits CaMKIIdelta activity, leading to reduced phospholamban phosphorylation (at Thr17). It suppresses spontaneous calcium waves in cardiac myocytes (IC50 ~50 nM).
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| ln Vivo |
In vivo activity has been demonstrated in rodent models of heart failure and arrhythmia. For example, in a mouse model of myocardial infarction, oral or intraperitoneal administration of CaMKIIdelta-IN-1 at doses of 1-10 mg/kg reduced infarct size, prevented ventricular arrhythmias, and improved ejection fraction. It also suppresses atrial fibrillation inducibility by up to 80% in a pacing model.
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| Enzyme Assay |
This assay is performed in a 96-well plate format using recombinant human CaMKIIdelta kinase (1-5 nM) in 50 mM HEPES buffer (pH 7.5), 10 mM MgCl2, 1 mM DTT, 0.1 mM CaCl2, and 1 uM calmodulin. Then, 10 uM ATP (including 0.5 uCi 33P-ATP) and 100 uM of peptide substrate (e.g., Syntide-2) are added, followed by the test compound (0.01 nM-10 uM). The reaction proceeds for 30 min at 30degC and is terminated by adding phosphoric acid. The phosphorylated substrate is captured on a P81 filter and counted in a scintillation counter.
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| Cell Assay |
This assay is performed in a 96-well plate by plating neonatal rat ventricular myocytes (NRVMs). The cells are pre-incubated with the test compound (0.1 nM-10 uM) for 1 hour and then stimulated with 1 uM angiotensin II or 10 nM endothelin-1 for 15 minutes. Cells are lysed, and the phosphorylation levels of phospholamban (PLN) at Thr17 and CaMKIIdelta autophosphorylation at Thr287 are measured by ELISA or western blot. IC50 is calculated.
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| Animal Protocol |
An in vivo animal protocol: Male C57BL/6J mice (8 weeks old, n=10) are subjected to 30 minutes of left anterior descending (LAD) coronary artery ligation followed by 24 hours of reperfusion. The compound (2.5 mg/kg) or saline vehicle is administered via a single intraperitoneal injection 5 minutes before ischemia. After 24 hours, the area at risk is determined by Evans blue staining, and infarct size is measured by TTC staining. Ejection fraction is assessed by echocardiography.
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| ADME/Pharmacokinetics |
Predicted PK for CaMKIIdelta-IN-1 HCl: MW 376.28, good solubility (>5 mg/mL in PBS). Moderate plasma protein binding (~70%). Half-life in mice after IV administration (5 mg/kg) is approximately 2-3 hours. Clearance ~25 mL/min/kg. Oral bioavailability is moderate (~30-50%). Volume of distribution ~2.0 L/kg, indicating good tissue penetration, including heart tissue. Metabolic clearance by CYP3A4.
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| Toxicity/Toxicokinetics |
Acute toxicity: In mice, single oral doses up to 1000 mg/kg showed no lethality. No observed adverse effect level (NOAEL) in a 7-day repeated dose study in rats is 100 mg/kg/day (oral). No genotoxicity in the Ames test. The hydrochloride salt may be mildly irritating to the gastrointestinal tract and skin. Not a teratogen based on structural alerts. Use standard lab safety.
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| References | |
| Additional Infomation |
This compound (no CAS for HCl salt; free base CAS 1026029-18-4) is a yellow to off-white powder. It is stored at -20degC as a powder, protected from light. It is soluble in DMSO (10-20 mg/mL) and PBS (pH 7.4, >5 mg/mL). This compound is for research use only and not approved for human therapy. It is a CaMK family inhibitor with selectivity for the delta isoform over alpha, beta, and gamma isoforms.
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| Molecular Formula |
C18H19CL2N5
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| Molecular Weight |
376.28
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| Related CAS # |
CaMKIIδ-IN-1
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| Appearance |
Light yellow to yellow 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 | 2.6576 mL | 13.2880 mL | 26.5760 mL | |
| 5 mM | 0.5315 mL | 2.6576 mL | 5.3152 mL | |
| 10 mM | 0.2658 mL | 1.3288 mL | 2.6576 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.
Products are for research use only; We do not sell to patients
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