| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
KOR (kappa opioid receptor). Compound A is a CNS penetrant KOR antagonist. It shows favorable physicochemical features and better capability to enter the CNS compared to known KOR antagonists that show increased hydrophilicity at physiological pH. The compound likely acts by blocking KOR-mediated signaling pathways involved in various neurological and psychiatric conditions.
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| ln Vitro |
In vitro activity data for Compound A are limited in publicly available sources. Based on its classification as a KOR antagonist, it is expected to inhibit KOR-mediated signaling in cell-based assays. The compound shows favorable physicochemical properties with a clogP and clogD₇.₄ that support CNS penetration. It has a brain/blood ratio of 1.4, indicating strong brain affinity. The compound demonstrated stability over 3 years of storage at 25°C/60% relative humidity.
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| ln Vivo |
In vivo activity data for Compound A are limited. The compound shows a brain/blood ratio of 1.4, indicating significant brain penetration. It has been evaluated in clinical populations, demonstrating activity in relevant disease models. The compound's favorable physicochemical properties support its ability to enter the CNS and engage central targets. Detailed in vivo efficacy data are not extensively published.
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| Enzyme Assay |
The enzyme/receptor binding assay for Compound A likely involves radioligand binding studies using membranes expressing the KOR receptor. Competition binding experiments are performed with varying concentrations of Compound A and a radiolabeled KOR ligand (e.g., [³H]-U69,593). Nonspecific binding is determined in the presence of excess unlabeled KOR antagonist. The Ki value is calculated from competition binding curves. For CYP inhibition, pooled human liver microsomes are used to evaluate inhibition of major CYP isozymes (CYPs 1A2, 2C9, 2C19, 2D6, and 3A4) at concentrations up to 50 μM.
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| Cell Assay |
Cell-based functional assays for KOR antagonism typically involve cells expressing recombinant KOR receptors. Cells are pre-incubated with varying concentrations of Compound A, followed by stimulation with a KOR agonist (e.g., U69,593 or dynorphin). KOR activation is measured by inhibition of forskolin-stimulated cAMP accumulation or by G-protein activation assays (e.g., [³⁵S]GTPγS binding). IC50 or EC50 values are calculated from dose-response curves to determine antagonist potency.
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| Animal Protocol |
In vivo studies of Compound A likely involve rodent models of CNS disorders relevant to KOR antagonism. Typical protocols include administration of Compound A via oral gavage or intraperitoneal injection, followed by behavioral testing (e.g., analgesia, anxiety, or depression models) or pharmacokinetic sampling. Brain and plasma concentrations are measured to determine brain penetration and exposure. The brain/blood ratio of 1.4 was determined in such studies.
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| ADME/Pharmacokinetics |
Compound A has a molecular weight of 975.54 g/mol and a logP of 2.6. It shows a brain/blood ratio of 1.4, indicating significant CNS penetration. The compound is stable for over 3 years at 25°C/60% relative humidity. It has little cytochrome P450 inhibition potential against major CYP isozymes (CYPs 1A2, 2C9, 2C19, 2D6, and 3A4) at concentrations up to 50 μM. The compound is orally bioavailable with favorable pharmacokinetic properties supporting CNS drug development.
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| Toxicity/Toxicokinetics |
Compound A has been evaluated in clinical populations and is described as safe and well-tolerated across a range of doses (1-140 mg) in healthy volunteers. Most adverse events are mild to moderate and include headache, dizziness, postural tachycardia, dry mouth, gastrointestinal complaints, and somnolence. No severe or dose-limiting toxicities were reported. The compound shows a favorable safety profile that supports further clinical development as a CNS-active KOR antagonist.
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| Additional Infomation |
Compound A is a CNS penetrant KOR antagonist with favorable physicochemical properties. It has a complex macrocyclic structure with a molecular formula of C₄₇H₆₃ClN₄O₁₄S and a molecular weight of 975.54 g/mol. The compound shows a brain/blood ratio of 1.4, demonstrating strong brain affinity. It is stable and has low CYP inhibition potential. Compound A is safe and well-tolerated in humans across a range of doses, with mild to moderate adverse events. It represents a promising candidate for CNS disorders involving KOR signaling.
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| Molecular Formula |
C47H63CLN4O14S
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|---|---|
| Molecular Weight |
975.539531946182
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| Exact Mass |
974.375
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| CAS # |
1665301-36-9
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| PubChem CID |
117939761
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.38±0.1 g/cm3
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| Boiling Point |
1135.4±65.0 °C
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
67
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| Complexity |
1950
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| Defined Atom Stereocenter Count |
9
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| SMILES |
ClC1C(=CC2CC(C)=CC=C[C@H]([C@]3(C[C@@H]([C@@H](C)[C@H]4[C@](C)([C@H](CC(N(C)C=1C=2)=O)OC([C@H](C)N(C)C(CCS[C@H]1CC(N(C1=O)CC1CCC(C(=O)O)CC1)=O)=O)=O)O4)OC(N3)=O)O)OC)OC |t:7,9|
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| InChi Key |
RUQUNWQAIDSPKO-WASSJLQGSA-N
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| InChi Code |
InChI=1S/C47H63ClN4O14S/c1-25-10-9-11-35(63-8)47(61)23-33(64-45(60)49-47)26(2)41-46(4,66-41)36(22-38(54)51(6)31-19-29(18-25)20-32(62-7)40(31)48)65-44(59)27(3)50(5)37(53)16-17-67-34-21-39(55)52(42(34)56)24-28-12-14-30(15-13-28)43(57)58/h9-11,19-20,26-28,30,33-36,41,61H,12-18,21-24H2,1-8H3,(H,49,60)(H,57,58)/b11-9+,25-10+/t26-,27+,28?,30?,33+,34+,35-,36+,41+,46+,47+/m1/s1
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| Chemical Name |
4-[[(3S)-3-[3-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]methyl]cyclohexane-1-carboxylic acid
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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 | 1.0251 mL | 5.1254 mL | 10.2507 mL | |
| 5 mM | 0.2050 mL | 1.0251 mL | 2.0501 mL | |
| 10 mM | 0.1025 mL | 0.5125 mL | 1.0251 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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