| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
IC50: 0.03 μM (cAK)[1]
PKA-IN-1 targets the catalytic subunit of cyclic AMP-dependent protein kinase (PKA), also known as cAMP-dependent protein kinase A catalytic subunit (cAK). PKA is a serine/threonine kinase that is activated by the second messenger cAMP. The enzyme consists of two regulatory subunits and two catalytic subunits; upon cAMP binding to the regulatory subunits, the catalytic subunits are released and become active. The catalytic subunit phosphorylates numerous downstream substrates, regulating diverse cellular functions. PKA-IN-1 specifically inhibits the catalytic activity of this subunit, blocking PKA-mediated phosphorylation of target proteins. The compound's high potency (IC₅₀ = 0.03 μM) and selectivity make it an excellent tool for studying PKA function. |
|---|---|
| ln Vitro |
In vitro studies have demonstrated that PKA-IN-1 is a highly efficient and selective inhibitor of PKA catalytic subunit with an IC₅₀ of 0.03 μM. The compound shows excellent selectivity over other kinases, minimizing off-target effects in cellular studies. In cell-based assays, PKA-IN-1 inhibits PKA-mediated phosphorylation of downstream substrates, blocking cAMP-induced cellular responses. The compound's potency is comparable to or better than other PKA inhibitors, making it a preferred tool for studying PKA signaling. PKA-IN-1 has been used to investigate the role of PKA in various cellular processes including apoptosis, differentiation, and metabolism.
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| ln Vivo |
In vivo activity data for PKA-IN-1 is limited in the published literature, as the compound is primarily used as a research tool in biochemical and cellular studies. The compound's high potency and selectivity suggest it could be useful for in vivo studies of PKA function, but comprehensive animal studies have not been extensively reported. Future studies may explore the compound's effects in animal models of diseases where PKA signaling is dysregulated. The compound's utility as a pharmacological probe for PKA function in vivo would require further characterization of its pharmacokinetic properties.
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| Enzyme Assay |
Cell-free biochemical assays for PKA-IN-1 typically measure inhibition of PKA catalytic activity using radiolabeled ATP or fluorescence-based methods. A standard protocol involves incubating the purified PKA catalytic subunit with varying concentrations of PKA-IN-1 (0.001-10 μM), a peptide substrate (e.g., Kemptide or a PKA-specific substrate), and [γ-³²P]ATP in kinase buffer at 30°C for 10-30 minutes. The reaction is terminated by spotting onto P81 phosphocellulose paper, washing with phosphoric acid, and counting incorporated radioactivity. Alternatively, fluorescence-based or luminescence-based kinase assays using labeled substrates can be used. IC₅₀ values are determined from dose-response curves using nonlinear regression analysis. Assays are performed in triplicate with appropriate positive and negative controls.
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| Cell Assay |
Cellular assays for PKA-IN-1 typically use cell lines expressing PKA to assess inhibition of PKA-mediated signaling. A standard protocol involves culturing cells in 96-well plates, treating with PKA-IN-1 at concentrations ranging from 0.01-10 μM for 1-24 hours, and stimulating with forskolin or other cAMP-elevating agents to activate PKA. PKA activity is assessed by measuring phosphorylation of PKA substrates (e.g., CREB) using Western blotting with phospho-specific antibodies. Alternatively, reporter assays using cAMP response element (CRE)-luciferase constructs can be used to measure PKA-dependent transcriptional activity. Cell viability is assessed by MTT or CellTiter-Glo assays to confirm that observed effects are not due to cytotoxicity.
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| Animal Protocol |
In vivo studies with PKA-IN-1 are limited, as the compound is primarily a research tool for in vitro applications. If conducted, a typical protocol might involve administration of PKA-IN-1 to rodents by intraperitoneal or intravenous injection, followed by assessment of PKA activity in target tissues. Tissue samples would be collected at various time points and analyzed for phosphorylation of PKA substrates by Western blotting. However, comprehensive in vivo efficacy studies have not been extensively reported for this compound. The compound's utility for in vivo studies would require formulation optimization and PK characterization.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for PKA-IN-1 is not extensively available in the published literature, as the compound is primarily used in research settings. The compound's molecular weight and physicochemical properties suggest reasonable cell permeability, as evidenced by its activity in cell-based assays. For in vivo studies, standard PK parameters including oral bioavailability, half-life, and clearance would need to be determined empirically. The compound is typically dissolved in DMSO for in vitro studies. Pharmacokinetic characterization would be necessary for any applications involving systemic administration.
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| Toxicity/Toxicokinetics |
Toxicological data specific to PKA-IN-1 is limited, as the compound is a research chemical used primarily in in vitro settings. At effective concentrations (0.03 μM for enzyme inhibition), the compound does not show significant cytotoxicity in most cell types. Higher concentrations may have off-target effects or cytotoxicity depending on the cell type and exposure duration. The compound's high selectivity for PKA over other kinases minimizes potential off-target toxicity. Standard laboratory safety precautions should be observed when handling this compound.
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| References | |
| Additional Infomation |
PKA-IN-1 is a research compound and not an approved drug. No clinical trials or regulatory approvals exist for this compound. It is commercially available from various suppliers for research use only. The compound's primary value lies in its utility as a highly potent and selective pharmacological tool for studying PKA-mediated signaling pathways. With an IC₅₀ of 0.03 μM, PKA-IN-1 enables researchers to dissect the roles of PKA in various cellular processes, including metabolism, gene expression, cell proliferation, and apoptosis. Its excellent selectivity minimizes off-target effects, making it a preferred inhibitor for PKA research.
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| Molecular Formula |
C13H11N3O
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|---|---|
| Molecular Weight |
225.25
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| Exact Mass |
225.09
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| CAS # |
179985-52-5
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| PubChem CID |
3691181
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| Appearance |
Off-white to pink solid powder
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| Density |
1.24g/cm3
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| Boiling Point |
489.7ºC at 760 mmHg
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| Melting Point |
200-202ºC
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| Flash Point |
250ºC
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| Vapour Pressure |
9.74E-10mmHg at 25°C
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| Index of Refraction |
1.632
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| LogP |
2.446
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
17
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| Complexity |
346
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C2=CC=CC=C2C(=N1)NC(=O)C)C#N
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| InChi Key |
SRNACQXBALMDDC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H11N3O/c1-8-12(7-14)10-5-3-4-6-11(10)13(15-8)16-9(2)17/h3-6H,1-2H3,(H,15,16,17)
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| Chemical Name |
N-(4-cyano-3-methylisoquinolin-1-yl)acetamide
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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) |
DMSO: 62.5 mg/mL (277.47 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (9.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4395 mL | 22.1976 mL | 44.3951 mL | |
| 5 mM | 0.8879 mL | 4.4395 mL | 8.8790 mL | |
| 10 mM | 0.4440 mL | 2.2198 mL | 4.4395 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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