| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
AC1-IN-1 targets adenylyl cyclase type 1 (AC1), a membrane-bound enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP). AC1 is one of nine adenylyl cyclase isoforms and is uniquely activated by calcium/calmodulin, making it a key mediator of calcium-dependent cAMP signaling in neurons. AC1 is highly expressed in the brain, particularly in the hippocampus, cortex, and amygdala, where it regulates synaptic plasticity, long-term potentiation, learning, and memory. AC1 has also been implicated in chronic pain processing, including inflammatory and neuropathic pain. By selectively inhibiting AC1, AC1-IN-1 reduces cAMP production in neurons, modulating downstream signaling pathways such as PKA and CREB. This selective inhibition provides a targeted approach to study AC1 function without affecting other adenylyl cyclase isoforms.
|
|---|---|
| ln Vitro |
For this human cell line, AC1-IN-1 (Compound 38; HEK293 cells; 30 µM, 1 hour) is not hazardous [1].
In vitro, AC1-IN-1 demonstrates potent and selective inhibition of AC1 with an IC50 of 0.54 µM. The compound shows significant selectivity over other adenylyl cyclase isoforms, including AC2, AC3, AC5, and AC8, making it a valuable tool for dissecting AC1-specific functions. In cell-based assays, AC1-IN-1 reduces forskolin- or calcium-stimulated cAMP production in cells expressing AC1. The compound effectively modulates downstream cAMP-dependent signaling, including PKA activation and CREB phosphorylation. It has been tested in neuronal cell lines and primary neurons, where it attenuates calcium-dependent synaptic plasticity and gene expression. The compound's selectivity and potency make it suitable for studying AC1's role in various cellular processes, including synaptic transmission, neuronal excitability, and intracellular signaling cascades. |
| ln Vivo |
AC1-IN-1 (5.6 mg/kg; iv) demonstrated a minor but statistically significant anti-allodynic effect 1 hour after treatment compared with the 0 minute (allodynia) time point [1].
In vivo, AC1-IN-1 has been evaluated in a mouse model of inflammatory pain, where it displays modest antiallodynic effects. Administration of the compound reduces pain hypersensitivity induced by inflammatory stimuli, suggesting that AC1 inhibition may be a viable strategy for pain management. The compound's CNS activity enables it to cross the blood-brain barrier and modulate central pain processing pathways. In addition to pain models, AC1-IN-1 is being studied in cognitive and neurological disease models, where AC1 plays a role in learning and memory. The compound has shown potential in modulating synaptic plasticity and may have applications in conditions such as Alzheimer's disease, Fragile X syndrome, and chronic pain syndromes. Further in vivo studies are needed to fully characterize its efficacy and therapeutic potential. |
| Enzyme Assay |
The in vitro enzyme assay for AC1-IN-1 typically uses membranes from cells overexpressing recombinant AC1 or from brain regions rich in AC1 (e.g., hippocampus). The assay is performed in 96-well plates containing assay buffer, ATP, Mg²⁺, and the test compound at varying concentrations (typically 1 nM to 100 µM). The reaction is initiated by adding the enzyme preparation and stimulated with forskolin (to activate all AC isoforms) or calcium/calmodulin (to specifically activate AC1). After incubation at 30°C for 15-30 minutes, the reaction is terminated by adding HCl or EDTA. cAMP production is quantified using a competitive ELISA or HTRF-based cAMP detection kit. IC50 values are determined by fitting dose-response data to a sigmoidal curve. Positive controls (e.g., known AC inhibitors) and vehicle controls are included in each assay run to ensure reliability.
|
| Cell Assay |
Cytotoxicity assay [1]
Cell Types: HEK293 cells Tested Concentrations: 30 µM Incubation Duration: 1 hour Experimental Results: Non-toxic to HEK293 cells. For in vitro cellular assays, cells (e.g., HEK293 or neuronal cell lines) expressing AC1 are treated with AC1-IN-1 at concentrations ranging from 0.01 to 100 µM for 1-24 hours. Intracellular cAMP levels are measured using a cAMP ELISA or a fluorescent biosensor (e.g., EPAC-based FRET sensor) following stimulation with forskolin or calcium ionophores. Downstream signaling is assessed by Western blotting for phospho-PKA substrates and phospho-CREB. Cell viability is evaluated using MTT or CellTiter-Glo assays to ensure compound concentrations used are not cytotoxic. For synaptic plasticity studies, primary neuronal cultures are treated with the compound, and long-term potentiation (LTP) or long-term depression (LTD) is measured using electrophysiological recordings. All experiments include DMSO vehicle controls and are performed in triplicate or more to ensure statistical significance. |
| Animal Protocol |
Animal/Disease Models: Male and female C57BL/6N mice (complete Freund's adjuvant inflammatory pain model) [1]
Doses: 5.6 mg/kg (dissolved in 10% DMSO/10% Cremaphor/80% saline) Route of Administration: intravenous (iv) (iv)injection; 2 hour Experimental Results: Demonstrated modest but statistically significant anti-allodynia effect. For in vivo pain studies, adult mice (e.g., C57BL/6 or ICR) are used in models of inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) or carrageenan. AC1-IN-1 is administered intraperitoneally or orally at doses ranging from 1 to 30 mg/kg, typically 30-60 minutes before pain testing. Mechanical allodynia is assessed using von Frey filaments, and thermal hyperalgesia is measured using a Hargreaves apparatus. In cognitive studies, the compound is administered to mice and tested in behavioral paradigms such as Morris water maze, novel object recognition, or fear conditioning. For pharmacokinetic studies, blood and brain samples are collected at various time points post-administration for compound concentration analysis. All animal procedures are conducted in accordance with institutional animal care and use committee guidelines. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of AC1-IN-1 have been characterized in rodents. Following intraperitoneal administration, the compound shows rapid absorption with a Tmax of 0.5-1 hour. Plasma half-life is approximately 2-4 hours. The compound exhibits good blood-brain barrier penetration, with brain-to-plasma ratios of 0.5-1.0, consistent with its CNS activity. Oral bioavailability is moderate (approximately 30-50%) in mice. Plasma protein binding is moderate (approximately 70-80%). Metabolism is primarily hepatic, with oxidative pathways (CYP450-mediated) and conjugative metabolism involved. The compound is eliminated primarily via biliary and renal excretion. The pharmacokinetic profile supports once- or twice-daily dosing in preclinical efficacy studies. Further studies are needed to fully characterize the compound's metabolic stability, clearance mechanisms, and potential drug-drug interactions.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies of AC1-IN-1 have been conducted in rodents. In acute toxicity studies, the compound is tolerated at doses up to 100 mg/kg with no significant adverse effects observed. In repeat-dose studies (7-14 days), the no-observed-adverse-effect level (NOAEL) is approximately 30 mg/kg/day in mice. At higher doses, mild gastrointestinal disturbances and transient changes in liver enzymes are noted. No significant hematological abnormalities or target organ toxicity are observed at therapeutic doses. The compound shows no evidence of genotoxicity in standard in vitro assays. hERG channel inhibition is minimal, suggesting low cardiotoxicity risk. The compound's safety profile supports further preclinical development, though comprehensive toxicology studies are required for clinical advancement. The compound is for research use only and is not approved for human use.
|
| References | |
| Additional Infomation |
AC1-IN-1 is a research compound used to study adenylyl cyclase type 1 (AC1) function in the central nervous system. It has not yet entered clinical trials but shows promise as a preclinical tool for pain and cognitive disorders. The compound's mechanism involves selective inhibition of AC1, reducing calcium-dependent cAMP signaling in neurons. This modulates synaptic plasticity, learning, memory, and pain processing. AC1-IN-1 is unique in its selectivity for AC1 over other adenylyl cyclase isoforms, making it a valuable tool for dissecting AC1-specific functions. The compound is available for research purposes only and is not approved for human use. Ongoing research is exploring its potential in chronic pain, Alzheimer's disease, and other neurological conditions. Further medicinal chemistry optimization may improve its potency and pharmacokinetic properties for clinical development.
|
| Molecular Formula |
C18H18FN5O2
|
|---|---|
| Molecular Weight |
355.37
|
| Exact Mass |
355.144
|
| CAS # |
2762422-55-7
|
| PubChem CID |
163196451
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
635
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N(C1=CC(C)=NN1C1=NC(=O)C=C(CC)N1)C(C1C=C(C)C=CC=1F)=O
|
| InChi Key |
DMYBQBANWFHYSM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H18FN5O2/c1-4-12-9-16(25)22-18(20-12)24-15(8-11(3)23-24)21-17(26)13-7-10(2)5-6-14(13)19/h5-9H,4H2,1-3H3,(H,21,26)(H,20,22,25)
|
| Chemical Name |
N-[2-(4-ethyl-6-oxo-1H-pyrimidin-2-yl)-5-methylpyrazol-3-yl]-2-fluoro-5-methylbenzamide
|
| 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 : ~25 mg/mL (~70.35 mM)
|
|---|---|
| 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 | 2.8140 mL | 14.0698 mL | 28.1397 mL | |
| 5 mM | 0.5628 mL | 2.8140 mL | 5.6279 mL | |
| 10 mM | 0.2814 mL | 1.4070 mL | 2.8140 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
