PF-4136309 is a potent, selective, and orally bioavailable CCR2 antagonist, with IC50s of 5.2 nM, 17 nM and 13 nM for human, mouse and rat CCR2.
For research use only. We do not sell to patients.
PF-4136309 Chemical Structure
CAS No. : 1341224-83-6
This product is a controlled substance and not for sale in your territory.
Based on 3 publication(s) in Google Scholar
Other Forms of PF-4136309:
(s)-PF-4136309
In-stock
(Rac)-PF-4136309
Get quote
PF-4136309 purchased from MedChemExpress. Usage Cited in:
Materials Today. 2022.
PGEM/PF-4136309 (PF) micelles exhibits potent anti-tumor efficacy. Tumor growth curve after combination of GEM (20 mg/kg; i.v) and PF (10 mg/kg; i.v). PGEM, an ultrasmall prodrug polymeric carrier of Gemcitabine (GEM).
Powered by Bioz
See more details on Bioz
View All CCR Isoform Specific Products:
View All Isoforms
Description
PF-4136309 is a potent, selective, and orally bioavailable CCR2 antagonist, with IC50s of 5.2 nM, 17 nM and 13 nM for human, mouse and rat CCR2.
IC50 & Target[1]
Human CCR2
5.2 nM (IC50)
Mouse CCR2
13 nM (IC50)
Rat CCR2
17 nM (IC50)
In Vitro
PF-4136309 is potent in human chemotaxis activity (IC50=3.9 nM) and in the whole blood assay (IC50=19 nM), with IC50 of 16 and 2.8 nM in mouse and rat chemotaxis assays. PF-4136309 is potent in inhibiting CCR2 mediated signaling events such as intracellular calcium mobilization and ERK (extracellular signal-regulated kinase) phosphorylation with IC50 values of 3.3 and 0.5 nM, respectively. In hERG patch clamp assay, PF-4136309 inhibits hERG potassium current with an IC50 of 20 μM. PF-4136309 is not a cytochrome P450 (CYP) inhibitor, with IC50 values of >30 μM against five major CYP isozymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Moreover, PF-4136309 is not a CYP inducer at concentrations up to 30 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PF-4136309 Related Antibodies
In Vivo
PF-4136309 (2 mg/kg) exhibits a moderate half-life in both species after iv administration (2.5 and 2.4 h). When administered orally, PF-4136309 (10 mg/kg) is absorbed rapidly, with peak concentration time (Tmax) at 1.2 h for rats and 0.25 h for dogs. A similar half-life is observed in both species between iv dosing and po dosing. PF-4136309 is well absorbed, with an oral bioavailability of 78% in both species[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvent & Solubility
In Vitro:
Ethanol : 133.33 mg/mL (234.49 mM; Need ultrasonic)
DMSO : ≥ 34 mg/mL (59.80 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : < 0.1 mg/mL (insoluble)
*"≥" means soluble, but saturation unknown.
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
1.7587 mL
8.7937 mL
17.5874 mL
5 mM
0.3517 mL
1.7587 mL
3.5175 mL
10 mM
0.1759 mL
0.8794 mL
1.7587 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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% EtOH 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (8.79 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (50.0 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% EtOH 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5 mg/mL (8.79 mM); Clear solution
This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (50.0 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% EtOH 90% Corn Oil
Solubility: ≥ 5 mg/mL (8.79 mM); Clear solution
This protocol yields a clear solution of ≥ 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 EtOH stock solution (50.0 mg/mL) to 900 μLCorn oil, and mix evenly.
Protocol 4
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 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 5
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 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 6
Add each solvent one by one: 10% DMSO 90% Corn Oil
This protocol yields a clear solution of ≥ 2.08 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 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
Protocol 7
Add each solvent one by one: 10% DMSO 90% Corn Oil
This protocol yields a clear solution of ≥ 2.08 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 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. 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: 0.5% Methylcellulose/saline water
Solubility: 10 mg/mL (17.59 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
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.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
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.
[1]. Xue CB, et al. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist. ACS Med. Chem. Lett., 2011, 2 (12), pp 913-918.
[Content Brief]
[2]. Wang W, Chen XK, Zhou L, et al. Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis. Acta Pharmacol Sin. Published online December 12, 2023.
[Content Brief]
[1]. Xue CB, et al. Discovery of INCB8761/PF-4136309, a Potent, Selective, and Orally Bioavailable CCR2 Antagonist. ACS Med. Chem. Lett., 2011, 2 (12), pp 913-918.
[2]. Wang W, Chen XK, Zhou L, et al. Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis. Acta Pharmacol Sin. Published online December 12, 2023.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO / Ethanol
1 mM
1.7587 mL
8.7937 mL
17.5874 mL
43.9684 mL
5 mM
0.3517 mL
1.7587 mL
3.5175 mL
8.7937 mL
10 mM
0.1759 mL
0.8794 mL
1.7587 mL
4.3968 mL
15 mM
0.1172 mL
0.5862 mL
1.1725 mL
2.9312 mL
20 mM
0.0879 mL
0.4397 mL
0.8794 mL
2.1984 mL
25 mM
0.0703 mL
0.3517 mL
0.7035 mL
1.7587 mL
30 mM
0.0586 mL
0.2931 mL
0.5862 mL
1.4656 mL
40 mM
0.0440 mL
0.2198 mL
0.4397 mL
1.0992 mL
50 mM
0.0352 mL
0.1759 mL
0.3517 mL
0.8794 mL
Ethanol
60 mM
0.0293 mL
0.1466 mL
0.2931 mL
0.7328 mL
80 mM
0.0220 mL
0.1099 mL
0.2198 mL
0.5496 mL
100 mM
0.0176 mL
0.0879 mL
0.1759 mL
0.4397 mL
PF-4136309 Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
