PF-4455242 hydrochloride

Name: PF-4455242 hydrochloride
Brand: MedChemExpress
SKU: HY-15691A
Rating: 4.5 (1 reviews)

Cat. No.: HY-15691A Purity: 99.01%: Data Sheet
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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.

PF-4455242 hydrochloride Chemical Structure

CAS No. : 1322001-35-3

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
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Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of PF-4455242 hydrochloride:

PF-04455242 Get quote

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•Related Screening Libraries:

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View All Opioid Receptor Isoform Specific Products:

View All Isoforms

μ Opioid Receptor/MOR κ Opioid Receptor/KOR δ Opioid Receptor/DOR NOP Receptor/ORL1

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mTOR mTORC1 mTORC2

Biological Activity
Purity & Documentation
References
Customer Review

Description

In Vitro

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 (K_i = 3 nM) to human KOR stably expressed in CHO cells, and also binds with high affinity to rat KOR stably expressed in CHO cells (K_i = 21 nM) as well as mouse primary forebrain KOR (K_i = 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 (K_i = 1.2 nM) than that against human MOR (K_i = 10 nM)^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

PF-04455242 (3.4 nM/day; i.c.v.; continuous infusion; 7 days) hydrochloride reduces body weight gain in ovariectomized wild-type female mice, an effect independent of food intake, accompanied by upregulated expression of thermogenic markers in adipose tissue and activation of the hypothalamic mTOR signaling pathway^[3].
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.

Animal Model:	C57BL/6 wild-type (female, 8-10 weeks old, ovariectomy-induced obesity)^[3]
Dosage:	3.4 nM/day
Administration:	i.c.v.; continuous infusion; 7 days
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).

Animal Model:	Sprague-Dawley (male, 175-200 g); Sprague-Dawley (male, jugular vein cannulated, 300-400 g)^[4]
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)
Administration:	s.c.; single dose; 1 hour before agonist administration
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.

Animal Model:	Sprague-Dawley (male, jugular vein cannulated, 300-400 g)^[4]
Dosage:	0.32, 1, 3.2, 10 mg/kg
Administration:	s.c.; single dose; 30 minutes before spiradoline
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.

Animal Model:	ICR (male, 25-30 g)^[4]
Dosage:	0.32, 1, 3.2 mg/kg/1, 3, 10 mg/kg
Administration:	s.c.; single dose; 1 hour before testing/s.c.; daily; 3 days, 30 minutes before each social defeat trial
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.

Molecular Weight

408.99

Formula

C₂₁H₂₉ClN₂O₂S

CAS No.

1322001-35-3

Appearance

Solid

Color

Light brown to gray

SMILES

O=S(C1=CC=CC=C1C2=CC=C(CNCC(C)C)C=C2)(N3CCCC3)=O.Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.4450 mL	12.2252 mL	24.4505 mL
5 mM	0.4890 mL	2.4450 mL	4.8901 mL
10 mM	0.2445 mL	1.2225 mL	2.4450 mL

View the 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.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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.

Protocol 1

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.
Protocol 2

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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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

Purity: 99.01%

Select Batch:

Data Sheet (284 KB) SDS (393 KB)

COA (253 KB) HNMR (265 KB) LCMS (103 KB)

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.

[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.

[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.

[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

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