| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
Compound 8a, Irdabisant (CEP-26401), exhibits inverse agonist activity with EC50 values of 2.0 nM and 1.1 nM against rat H3R and human H3R, respectively, and has Kb antagonist activity against both H3Rs with app values of 1.0 nM and 0.4 nM, respectively[1]. In addition to muscarinic M2 (Ki = 3.7 ± 0.0 μM) and adrenergic α1A (Ki = 9.8 ± 0.3 μM) receptors, irdabisant also exhibits activity against norepinephrine (Ki = 10 ± 1 μM), dopamine transporter (Ki = 11 ± 2 μM), and phosphodiesterase PDE3 (IC50 = 15 ± 1 μM) [1]. With IC50 values more than 30 μM, irdabisant inhibits the cytochrome P450 enzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 [1]. This suggests a low risk of drug interactions.
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| ln Vivo |
The H3R agonist RAMH-induced smoking is dose-dependently inhibited by CEP-26401 (0.01-0.3 mg/kg; oral; single dose) [1]. In a social recognition short-term memory model, CEP-26401 (0.0001-0.1 mg/kg; intravenously or orally; single dose) enhances rat performance [1]. Rats treated orally with CEP-26401 (3–30 mg/kg; single dose) show wake-promoting effects [2]. In DBA/2NCrl mice, CEP-26401 (3–30 mg/kg; intraperitoneally) raises prepulse inhibition (PPI) [2]. CEP-26401 (1 mg/kg IV, 3 mg/kg PO; single dose) exhibits a moderate clearance rate in dogs and monkeys relative to rats rate, high oral bioavailability, and rapid absorption in rats and monkeys[1]. Irdabisant (compound 8a) pharmacokinetic parameters in rats, dogs, and monkeys [1]. Rat dog monkey IV t1/2 (h) 2.6 2.9 5.4 iv Vd (L/kg) 9.4 3.5 ± 1.1 3.8 ± 0.9 iv CL (mL/min/kg) 42 13.2 ± 1.5 7.7 ± 1.8 po t1/2 (L /kg) 2.9 2.7 5.0 po AUC (ng·h/mL) 984 1190 ± 180 1919 ± 611 po Cmax (ng/mL) 270 230 ± 70 760 ± 74 po F (%) 83 22 ± 2 83 ± 18 Brain to Plasma ratio 2.6 ± 0.2 2.4 ± 0.4 /
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (addiction model induced by intraperitoneal (ip) injection of 10 mg/kg RAMH) [1]
Doses: 0.01-0.3 mg/kg Route of Administration: oral; single Dose Experimental Results: Dose-dependent inhibition of water drinking induced by the H3R agonist RAMH (shown as water drinking), with an EC50 value of 0.06 mg/kg. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (adult rats are briefly exposed to juvenile rats to establish a social recognition model) [2] Doses: intraperitoneal (ip) injection 0.0001, 0.001, 0.01 and 0.1 mg/kg; oral 0.01 and 0.1 mg/kg Route of Administration: iv or po; single-dose Experimental Results: effective rate reduction over study duration (RID) across the 0.001 to 0.1 mg/kg ip dose range and 0.01 to 0.1 mg/kg po dose range, demonstrating this model Effective enhancement of short- and medium-term sensory memory. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [2] Doses: 3, 10 and 30 mg/kg Route of Administration: Oral; Single Dose Experimental Results: 90% of treated animals within 3 hrs (hrs (hours)) of 30 mg/kg dose of time in the a |
| References |
|
| Molecular Formula |
C18H24CLN3O2
|
|---|---|
| Molecular Weight |
349.855063438416
|
| Exact Mass |
349.156
|
| CAS # |
1005398-61-7
|
| Related CAS # |
Irdabisant;1005402-19-6
|
| PubChem CID |
53363810
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.842
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
24
|
| Complexity |
467
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
Cl.O(C1C=CC(C2C=CC(NN=2)=O)=CC=1)CCCN1CCC[C@H]1C
|
| InChi Key |
WJUJICMNSMPLLG-PFEQFJNWSA-N
|
| InChi Code |
InChI=1S/C18H23N3O2.ClH/c1-14-4-2-11-21(14)12-3-13-23-16-7-5-15(6-8-16)17-9-10-18(22)20-19-17;/h5-10,14H,2-4,11-13H2,1H3,(H,20,22);1H/t14-;/m1./s1
|
| Chemical Name |
3-[4-[3-[(2R)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1H-pyridazin-6-one;hydrochloride
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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 | 2.8583 mL | 14.2914 mL | 28.5829 mL | |
| 5 mM | 0.5717 mL | 2.8583 mL | 5.7166 mL | |
| 10 mM | 0.2858 mL | 1.4291 mL | 2.8583 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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