| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
NK3R
Pavinetant targets the neurokinin-3 (NK3) receptor, also known as the tachykinin receptor 3 (TACR3). NK3 receptors are G protein-coupled receptors involved in the regulation of various physiological processes, including the release of neurotransmitters such as dopamine and serotonin. By antagonizing NK3 receptors, Pavinetant modulates neurotransmitter signaling pathways implicated in psychiatric disorders. The compound is a selective NK3 receptor antagonist developed for the treatment of schizophrenia and menopausal symptoms. |
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| ln Vitro |
Pavinetant (AZD2624) is a strong and focused antagonist of the NK3 receptor that was created to treat schizophrenia. The microsomal CYP3A4/5 activities are inhibited by the pavinetant, as demonstrated by apparent IC50 values of 19.8 μM for testosterone and 7.1 μM for midazolam assays, respectively. There is no evidence of a time-dependent Pavinetant-induced inactivation of CYP3A4/5 activity. Pavinetant inhibits CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 weakly to nonexistently[1].
In vitro, Pavinetant demonstrates potent and selective antagonistic activity against the NK3 receptor. The compound shows inhibitory effects on microsomal CYP3A4/5 activity, with apparent IC50 values of 7.1 and 19.8 μM for imidazolam and testosterone assays, respectively. No time-dependent inactivation of CYP3A4/5 activity was observed. Specific cellular assay data, such as IC50 values for NK3 receptor antagonism, are not detailed in the available sources beyond its characterization as a potent antagonist. |
| ln Vivo |
Pavinetant has been evaluated in clinical trials for the treatment of schizophrenia and menopausal symptoms. As of 2017, the drug was in phase II clinical trials for hot flashes and polycystic ovary syndrome (PCOS). The compound is orally active, supporting its use in clinical studies. Specific in vivo efficacy data from animal models are not detailed in the available sources, but the compound's progression to clinical trials indicates promising preclinical activity.
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| Enzyme Assay |
Pavinetant (AZD2624) is tested for its ability to inhibit CYP3A activities in a time-dependent manner by pre-incubating 10 μM of Pavinetant in 0.2 mL of 0.1 M pH 7.4 phosphate buffer, which contains 1 mM NADPH and 2 mg/mL HLM, at 37°C for 0, 3, 10, 20, and 30 minutes. Furthermore, as a positive control, verapamil is tested at 10 μM and incubated separately. For every time point, an aliquot of 20 μL is taken out of the pre-incubation tube and added to 180 μL of a secondary 5-min incubation that contains 1 mM NADPH and 15 μM midazolam. CYP3A enzymes are detected by LC-MS analysis of the 1′-hydroxymidazolam formation, which serves as a marker activity. The post-pre-incubation CYP3A enzyme activities with and without the Pavinetant pre-incubation are compared to the activities after the vehicle solvent (1% methanol) incubation[1].
The NK3 receptor binding assay for Pavinetant involves incubating the compound with membrane preparations from cells expressing the human NK3 receptor and a radiolabeled NK3 ligand (such as [³H]-SB 222200 or a related compound). After incubation at room temperature for an appropriate period, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 or Ki for displacement of the radioligand is calculated from the competition curve. Functional antagonism can be assessed using calcium mobilization assays. |
| Cell Assay |
To evaluate the cellular activity of Pavinetant, cells expressing the human NK3 receptor (such as CHO or HEK293 cells) are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye. Cells are pre-incubated with varying concentrations of Pavinetant and then stimulated with an NK3 receptor agonist (such as senktide or neurokinin B). The intracellular calcium flux is measured using a fluorescence plate reader. The IC50 for inhibition of agonist-induced calcium flux is calculated. The compound's selectivity can be assessed by testing against other neurokinin receptors (NK1 and NK2).
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| Animal Protocol |
Specific in vivo animal experiment protocols for Pavinetant are not detailed in the available sources. As an orally active NK3 receptor antagonist, the compound has likely been evaluated in animal models of psychiatric disorders and menopausal symptoms. Typical studies would involve administering Pavinetant orally to rodents and assessing effects on behaviors relevant to schizophrenia (such as prepulse inhibition or hyperlocomotion) or on thermoregulatory responses relevant to hot flashes. However, specific protocols are not described in the available literature.
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| ADME/Pharmacokinetics |
Pavinetant is characterized as being orally active. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 459.6 and a molecular formula of C26H25N3O3S. It is a small molecule with properties suitable for oral administration. As a compound that has advanced to clinical trials, its pharmacokinetic profile has likely been characterized in preclinical species and in humans.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Pavinetant are not provided in the available sources. However, the compound has been evaluated in clinical trials for schizophrenia and menopausal symptoms, indicating that its safety profile has been assessed in humans. As of 2017, the drug was in phase II clinical trials for hot flashes and PCOS. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Pavinetant belongs to the quinoline class of compounds and is an amide formed by the condensation of the carboxyl group of 3-[(methanesulfonyl)amino]-2-phenylquinoline-4-carboxylic acid with the amino group of (1S)-1-phenylprop-1-amine. It is a neurokinin-3 receptor antagonist and has been tested as a potential treatment for schizophrenia and menopausal symptoms. It is both a neurokinin-3 receptor antagonist and an antipsychotic. Pavinetant belongs to the quinoline, secondary amide, sulfonamide, and aromatic amide classes of compounds. Pavinetant has been used in trials investigating its safety and treatment of schizophrenia.
Pavinetant is also known as AZD2624 and MLE4901. It is an orally active, selective neurokinin-3 (NK3) receptor antagonist originally developed by AstraZeneca and Millendo. It has been trialled as a potential drug for the treatment of schizophrenia and menopausal symptoms. As of 2017, the drug was in phase II clinical trials for hot flashes and PCOS. It is a member of the quinolines class and has a role as a neurokinin-3 receptor antagonist and an antipsychotic agent. |
| Molecular Formula |
C26H25N3O3S
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|---|---|
| Molecular Weight |
459.56000494957
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| Exact Mass |
459.162
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| Elemental Analysis |
C, 67.95; H, 5.48; N, 9.14; O, 10.44; S, 6.98
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| CAS # |
941690-55-7
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| PubChem CID |
23649245
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| Appearance |
White to off-white solid powder
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| LogP |
6.883
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
740
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(C1C2C=CC=CC=2N=C(C2C=CC=CC=2)C=1NS(=O)(=O)C)(=O)N[C@H](C1C=CC=CC=1)CC
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| InChi Key |
QYTBBBAHNIWFOD-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C26H25N3O3S/c1-3-21(18-12-6-4-7-13-18)28-26(30)23-20-16-10-11-17-22(20)27-24(19-14-8-5-9-15-19)25(23)29-33(2,31)32/h4-17,21,29H,3H2,1-2H3,(H,28,30)/t21-/m0/s1
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| Chemical Name |
3-(methanesulfonamido)-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide
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| Synonyms |
MLE-4901; MLE4901; MLE 4901; AZD-4901; AZD 4901; AZD4901; AZD-2624; AZD2624; AZD 2624; AZ-12472520; AZ 12472520; AZ12472520
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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: ≥ 50 mg/mL (~108.8 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (6.53 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 30.0 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: ≥ 3 mg/mL (6.53 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 30.0 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 | 2.1760 mL | 10.8800 mL | 21.7599 mL | |
| 5 mM | 0.4352 mL | 2.1760 mL | 4.3520 mL | |
| 10 mM | 0.2176 mL | 1.0880 mL | 2.1760 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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