PF-4455242 hydrochloride
Based on 1 Customer Validation
PF-4455242 hydrochloride is an orally bioavailable, blood-brain barrier-permeable κ-opioid receptor (KOR) inhibitor. PF-4455242 hydrochloride blocks in vivo effects induced by KOR and MOR agonists, and elicits KOR-independent outward currents in ventral tegmental area neurons. PF-4455242 hydrochloride promotes energy expenditure and activates the hypothalamic mTOR pathway. PF-4455242 hydrochloride attenuates stress-induced behavioral effects and produces antidepressant-like effects. PF-4455242 hydrochloride can be used in studies related to pain, depression, addictive disorders, and obesity induced by estrogen withdrawal.
For research use only. We do not sell to patients.
- Purity: 99.01%
- CAS No.: 1322001-35-3
- Formula: C21H29ClN2O2S
- Molecular Weight:408.99
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
All Opioid Receptor Isoforms
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Biological Activity
PF-04455242 (100 nM-1 μM) hydrochloride is a partial κ-opioid receptor antagonist with an IC50 of 6.7 nM in dopamine neurons of the rat ventral tegmental area (VTA); at concentrations of 100 nM and 1 μM, it induces outward K+ currents in a subset of these neurons[2].
PF-04455242 (60 minutes at room temperature) hydrochloride binds with high affinity (Ki = 3 nM) to human KOR stably expressed in CHO cells, and also binds with high affinity to rat KOR stably expressed in CHO cells (Ki = 21 nM) as well as mouse primary forebrain KOR (Ki = 22 nM)[4].
PF-04455242 (treated at 30°C for 20 min; treated at 30°C for 30 min) hydrochloride acts as an antagonist of human KOR stably expressed in CHO cells, with higher potency (Ki = 1.2 nM) than that against human MOR (Ki = 10 nM)[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PF-04455242 (0.32-10 mg/kg; s.c.; single dose; 1 h before agonist administration) hydrochloride dose-dependently blocks the analgesic effects induced by KOR and MOR agonists in rats, and achieves dose-dependent, time-limited target binding to KOR and MOR in rat brains[4].
PF-04455242 (0.32-10 mg/kg; s.c.n; single administration; 30 minutes prior to Spiradoline treatment) hydrochloride dose-dependently blocks Spiradoline (HY-106756)-induced elevation of plasma prolactin in rats, with an ED50 of 2.3 mg/kg[4].
PF-04455242 (0.32-10 mg/kg; s.c.; single administration; 1 h before testing) hydrochloride exhibits antidepressant-like efficacy in the mouse forced swim test, alleviates depression-like social defeat behavior in mice following repeated stress exposure, and prevents stress-induced reinstatement of extinguished cocaine-seeking behavior in mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 wild-type (female, 8-10 weeks old, ovariectomy-induced obesity)[3]
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Dosage:3.4 nM/day
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Administration:i.c.v.; continuous infusion; 7 days
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Result:Significantly reduced cumulative body weight gain compared to vehicle control (p < 0.05).
Showed no change in cumulative food intake.
Demonstrated a non-significant tendency toward reduced subcutaneous inguinal white adipose tissue depots (p = 0.07).
Significantly increased uncoupling protein 1-positive immunostaining in brown adipose tissue (p < 0.05) and subcutaneous inguinal white adipose tissue (p < 0.05) compared to vehicle control.
Significantly increased phosphorylated levels of mTOR (pmTOR) and phosphorylated S6 (pS6) in the medio-basal hypothalamic area (p < 0.01).
Showed a non-significant tendency toward increased phosphorylated p70S6K (pS6K) levels in the medio-basal hypothalamic area (p = 0.06).
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Animal Model:Sprague-Dawley (male, 175-200 g); Sprague-Dawley (male, jugular vein cannulated, 300-400 g)[4]
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Dosage:0.32, 1, 3.2, 10, 17.8, 32 mg/kg/0.1, 1, 3.2, 10, 32 mg/kg; 10 mg/kg (time-course)
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Administration:s.c.; single dose; 1 hour before agonist administration
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Result:Attenuated Spiradoline-induced tail-flick latency with an EC50 of 1.5 mg/kg.
Attenuated Morphine-induced tail-flick latency with an EC50 of 9.8 mg/kg.
Inhibited ex vivo [3H]CI977 binding to KORs with an ID50 of 2.0 mg/kg.
Inhibited ex vivo [3H]DAMGO binding to MORs with an ID50 of 8.6 mg/kg.
At 10 mg/kg, inhibited ex vivo [3H]CI977 binding by 60% at 15 minutes post-dose, reached maximal 82% inhibition at 30 minutes, maintained inhibition for 2 h, and showed no inhibition by 8 hours.
Inhibited in vivo [3H]PF-04767135 binding to KORs with an ID50 of 5.2 mg/kg.
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Animal Model:Sprague-Dawley (male, jugular vein cannulated, 300-400 g)[4]
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Dosage:0.32, 1, 3.2, 10 mg/kg
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Administration:s.c.; single dose; 30 minutes before spiradoline
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Result:Dose-dependently reduced Spiradoline-induced plasma prolactin elevation with an ED50 of 2.3 mg/kg.
At 3.2 or 10 mg/kg, had no effect on basal prolactin levels.
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Animal Model:ICR (male, 25-30 g)[4]
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Dosage:0.32, 1, 3.2 mg/kg/1, 3, 10 mg/kg
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Administration:s.c.; single dose; 1 hour before testing/s.c.; daily; 3 days, 30 minutes before each social defeat trial
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Result:Reduced immobility with a minimal effective dose of 3.2 mg/kg.
Dose-dependently reduced time spent in defeated postures: the 3 mg/kg dose produced a significant reduction on day 2, and all three doses produced significant reductions on day 3.
Chemical Information
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CAS No. 1322001-35-3
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Appearance Solid
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Molecular Weight 408.99
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Formula C21H29ClN2O2S
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Color Light brown to gray
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SMILES
O=S(C1=CC=CC=C1C2=CC=C(CNCC(C)C)C=C2)(N3CCCC3)=O.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 50 mg/mL (122.25 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (284 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Naganawa M, et al. Evaluation of the agonist PET radioligand [¹¹C]GR103545 to image kappa opioid receptor in humans: kinetic model selection, test-retest reproducibility and receptor occupancy by the antagonist PF-4455242 hydrochloride. Neuroimage. 2014;99:69-79. [Content Brief]
[2]. Margolis EB, et al. Differential effects of novel kappa opioid receptor antagonists on dopamine neurons using acute brain slice electrophysiology. PLoS One. 2020;15(12):e0232864. Published 2020 Dec 29. [Content Brief]
[3]. Romero-Picó A, et al. Kappa-Opioid Receptor Blockade Ameliorates Obesity Caused by Estrogen Withdrawal via Promotion of Energy Expenditure through mTOR Pathway. Int J Mol Sci. 2022;23(6):3118. Published 2022 Mar 14. [Content Brief]
[4]. Grimwood S, et al. Pharmacological characterization of 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine (PF-4455242 hydrochloride), a high-affinity antagonist selective for κ-opioid receptors. J Pharmacol Exp Ther. 2011;339(2):555-566. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4450 mL | 12.2252 mL | 24.4505 mL | 61.1262 mL |
| 5 mM | 0.4890 mL | 2.4450 mL | 4.8901 mL | 12.2252 mL | |
| 10 mM | 0.2445 mL | 1.2225 mL | 2.4450 mL | 6.1126 mL | |
| 15 mM | 0.1630 mL | 0.8150 mL | 1.6300 mL | 4.0751 mL | |
| 20 mM | 0.1223 mL | 0.6113 mL | 1.2225 mL | 3.0563 mL | |
| 25 mM | 0.0978 mL | 0.4890 mL | 0.9780 mL | 2.4450 mL | |
| 30 mM | 0.0815 mL | 0.4075 mL | 0.8150 mL | 2.0375 mL | |
| 40 mM | 0.0611 mL | 0.3056 mL | 0.6113 mL | 1.5282 mL | |
| 50 mM | 0.0489 mL | 0.2445 mL | 0.4890 mL | 1.2225 mL | |
| 60 mM | 0.0408 mL | 0.2038 mL | 0.4075 mL | 1.0188 mL | |
| 80 mM | 0.0306 mL | 0.1528 mL | 0.3056 mL | 0.7641 mL | |
| 100 mM | 0.0245 mL | 0.1223 mL | 0.2445 mL | 0.6113 mL |
PF-4455242 hydrochloride Related Classifications
HY-15691A Related Classifications
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