| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
The primary target of NKY80 is adenylyl cyclase type V (AC5), one of the nine membrane-bound isoforms of adenylyl cyclase. AC5 is predominantly expressed in the heart and brain, where it plays a critical role in regulating cAMP production and downstream signaling pathways. NKY80 acts as a non-competitive inhibitor of AC5 with an IC50 of 8.3 μM. It also inhibits AC3 (IC50 = 132 μM) and AC2 (IC50 = 1.7 mM) but with significantly lower potency. The compound's selectivity for AC5 over other AC isoforms makes it a valuable tool for studying AC5-specific functions. By inhibiting AC5, NKY80 reduces cAMP production, thereby modulating downstream signaling pathways, including protein kinase A (PKA) and cAMP response element-binding protein (CREB).
|
|---|---|
| ln Vitro |
At its maximum concentration of 10 nM, NKY80 (20 μM) bursts, resulting in increased levels of ventricular cAMP and LVP [2]. In isolated JG cells, NKY80 (20 μM; 2 hours) entirely bursts increases in cAMP concentration and renin release [3].
In vitro, NKY80 is a potent, selective, and non-competitive inhibitor of adenylyl cyclase type V with an IC50 of 8.3 μM. It inhibits AC3 with an IC50 of 132 μM and AC2 with an IC50 of 1.7 mM. NKY80 (20 μM; 2 hours) completely blocks the increase in both cAMP content and renin release from isolated juxtaglomerular (JG) cells. The compound modulates AC catalytic activity in cardiac and lung tissues. Its activity is typically measured using adenylyl cyclase enzyme assays that monitor the conversion of ATP to cAMP, with IC50 values determined from dose-response curves. The compound's non-competitive mechanism of inhibition has been characterized through kinetic studies. |
| ln Vivo |
In vivo, NKY80 is used to probe AC signaling and cAMP-regulated physiological processes. The compound's ability to modulate AC activity in cardiac and lung tissues makes it a valuable tool for studying cardiovascular and respiratory diseases. By inhibiting AC5, NKY80 can reduce cAMP production, which may have effects on cardiac contractility, heart rate, and vascular tone. The compound's cell-permeable nature facilitates its use in in vivo studies. While specific in vivo efficacy data for NKY80 are not extensively detailed in the available literature, its mechanism of action suggests that it would be effective in modulating cAMP-mediated signaling pathways in vivo.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for NKY80 involve adenylyl cyclase enzyme assays using purified AC isoforms or membrane preparations from tissues expressing specific AC isoforms. The compound's inhibitory activity is measured by monitoring the conversion of ATP to cAMP in the presence of the enzyme and varying concentrations of NKY80. cAMP production is typically quantified using radioimmunoassay (RIA), ELISA, or other detection methods. IC50 values are determined from dose-response curves. Kinetic studies are performed to characterize the mechanism of inhibition, with NKY80 demonstrating non-competitive inhibition. Selectivity profiling against other AC isoforms (AC1, AC2, AC3, AC4, AC6, AC7, AC8, AC9) is performed to assess the compound's specificity.
|
| Cell Assay |
In vitro cellular assays for NKY80 are conducted in cell lines that express AC5 or other AC isoforms. Cells are treated with varying concentrations of NKY80, and intracellular cAMP levels are measured using ELISA, radioimmunoassay, or fluorescence-based methods. The compound's ability to inhibit cAMP production in response to forskolin or other AC activators is assessed. In isolated juxtaglomerular (JG) cells, NKY80 (20 μM; 2 hours) completely blocks the increase in both cAMP content and renin release. These assays confirm that NKY80 engages its target in a cellular context and produces the expected inhibition of AC activity and downstream signaling.
|
| Animal Protocol |
In vivo animal studies for NKY80 would typically be conducted in animal models of cardiovascular or respiratory diseases where AC5 is implicated. Animals would be administered the compound, and outcomes would be assessed based on the specific disease model. For example, in models of heart failure, the compound's effects on cardiac contractility and cAMP levels could be assessed. In models of pulmonary hypertension, its effects on vascular tone and cAMP signaling in the lungs could be evaluated. Pharmacokinetic studies would be performed to determine the compound's bioavailability, half-life, and tissue distribution. The compound's cell-permeable nature facilitates its use in vivo.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NKY80 indicate that it has a molecular weight of 229.23 and a molecular formula of C12H11N3O2. The compound is soluble in DMSO (up to 40 mg/ml) and ethanol (up to 5 mg/ml with warming). It is cell-permeable, facilitating its use in cellular assays. For storage, the powder should be kept under appropriate conditions to maintain stability. Its purity is typically ≥95%. The compound's molecular weight and physicochemical properties suggest that it has favorable drug-like characteristics. Its non-nucleoside quinazolinone structure distinguishes it from other AC inhibitors.
|
| Toxicity/Toxicokinetics |
Toxicological information for NKY80 is primarily derived from its use as a research compound in preclinical studies. As an AC5 inhibitor, potential on-target effects could include changes in cardiac function, given the role of AC5 in the heart. Comprehensive toxicology studies would be required for therapeutic development, including assessments of cardiovascular, neurological, and metabolic function. However, NKY80 is primarily used as a research tool and has not advanced to clinical development.
|
| References |
|
| Additional Infomation |
NKY80 is a potent, selective, and non-competitive inhibitor of adenylyl cyclase type V (AC5). It has IC50 values of 8.3 μM for AC5, 132 μM for AC3, and 1.7 mM for AC2. NKY80 (20 μM; 2 hours) completely blocks cAMP increase and renin release from isolated JG cells. The compound is a non-nucleoside quinazolinone that modulates AC activity in cardiac and lung tissues. NKY80 is not approved for clinical use and is available from research chemical suppliers for preclinical studies.
|
| Molecular Formula |
C12H11N3O2
|
|---|---|
| Molecular Weight |
229.24
|
| Exact Mass |
229.085
|
| Elemental Analysis |
C, 62.87; H, 4.84; N, 18.33; O, 13.96
|
| CAS # |
299442-43-6
|
| PubChem CID |
2772368
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
2.145
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
17
|
| Complexity |
310
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=COC(=C1)C2CC3=NC(=N)NC=C3C(=O)C2
|
| InChi Key |
SOJUSNIBPPMLCC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C12H11N3O2/c13-12-14-6-8-9(15-12)4-7(5-10(8)16)11-2-1-3-17-11/h1-3,6-7H,4-5H2,(H2,13,14,15)
|
| Chemical Name |
2-amino-7-(furan-2-yl)-7,8-dihydro-6H-quinazolin-5-one
|
| Synonyms |
NKY-80; NKY 80; NKY80
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~1090.61 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (9.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (9.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (9.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3622 mL | 21.8112 mL | 43.6224 mL | |
| 5 mM | 0.8724 mL | 4.3622 mL | 8.7245 mL | |
| 10 mM | 0.4362 mL | 2.1811 mL | 4.3622 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
