| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
ITK (IC50 = 2 nM)
PF-06465469 targets ITK (IL-2-inducible T cell kinase), a member of the Tec family of non-receptor tyrosine kinases that is primarily expressed in T cells. ITK plays a critical role in T cell receptor (TCR) signaling, where it is activated downstream of the TCR and contributes to the activation of phospholipase C-γ1 (PLCγ1), calcium mobilization, and nuclear factor of activated T cells (NFAT) activation. ITK is involved in T cell proliferation, differentiation, and cytokine production. PF-06465469 is a covalent inhibitor that forms an irreversible bond with ITK, resulting in sustained inhibition. The compound also inhibits BTK (Bruton's tyrosine kinase) with an IC50 of 2 nM. PF-06465469 demonstrates potent in vitro activity as an ITK inhibitor with an IC50 of 2 nM. The compound also inhibits BTK with an IC50 of 2 nM. The compound's covalent binding mechanism ensures sustained inhibition of its targets. PF-06465469's potent ITK and BTK inhibition makes it a valuable tool for studying the role of these kinases in T cell and B cell signaling, immune responses, and potential therapeutic applications in autoimmune diseases and cancer. |
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| ln Vitro |
In vivo efficacy data for PF-06465469 are not extensively documented in publicly available sources. Based on its potent inhibition of ITK and BTK, the compound is expected to have potential utility in models of autoimmune diseases, inflammatory disorders, or B cell malignancies. ITK is a key regulator of T cell activation, and BTK is a critical component of B cell receptor signaling. PF-06465469's covalent inhibition of both kinases may offer advantages in terms of sustained target inhibition. Further in vivo studies are needed to fully characterize the compound's therapeutic potential, including its efficacy in disease models, pharmacokinetic properties, and safety profile.
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| ln Vivo |
The in vitro enzyme inhibition assay for PF-06465469 measures the inhibition of ITK and BTK kinase activities. Recombinant human ITK or BTK enzymes are incubated with varying concentrations of PF-06465469 (typically ranging from picomolar to micromolar) in the presence of ATP and a peptide substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of substrate phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or radiometric measurement. IC50 values are determined by fitting dose-response curves to the inhibition data (2 nM for ITK, 2 nM for BTK). The covalent binding mechanism can be confirmed by pre-incubation studies or mass spectrometry. The compound is dissolved in DMSO and diluted in assay buffer. Appropriate positive controls and negative controls are included in each assay run.
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| Enzyme Assay |
The in vitro cellular assay for PF-06465469 is performed using T cell lines (for ITK) or B cell lines (for BTK). Cells are cultured in appropriate medium and treated with varying concentrations of PF-06465469 or vehicle control (DMSO) for specified time points. ITK or BTK phosphorylation and downstream signaling proteins (e.g., PLCγ1, AKT, ERK) are assessed by Western blotting using phospho-specific antibodies. T cell activation (e.g., IL-2 production, CD69 upregulation) or B cell activation (e.g., calcium flux, proliferation) is measured to assess the functional effects of kinase inhibition. Cell viability and proliferation are assessed using assays such as MTT or CellTiter-Glo. Dose-response relationships are established by analyzing signaling inhibition and functional responses across different compound concentrations.
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| Cell Assay |
In vivo animal experiments with PF-06465469 are not extensively described in publicly available sources. Based on its in vitro activity, potential in vivo studies would likely use mouse models of autoimmune diseases (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis) or B cell malignancies. PF-06465469 would be administered via oral gavage or intraperitoneal injection at various doses. Disease progression would be monitored using clinical scores, histology, and measurement of inflammatory markers or tumor burden. At study endpoint, tissues would be harvested for analysis of ITK and BTK target engagement, downstream signaling, and markers of immune cell activation. The compound's efficacy would be evaluated by comparing disease severity in treated versus control groups.
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| Animal Protocol |
Detailed pharmacokinetic (PK) parameters for PF-06465469 are not extensively documented in publicly available sources. The compound has a molecular weight of 523.63 and a chemical formula of C30H33N7O2. PF-06465469 is soluble in DMSO for formulation purposes. For in vivo administration, the compound would need to be formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are not available from the current search results and would require consultation of the primary literature.
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| ADME/Pharmacokinetics |
Comprehensive toxicological data for PF-06465469 are not extensively documented in publicly available sources. As a research-grade compound, PF-06465469 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| Toxicity/Toxicokinetics |
PF-06465469 is a research compound developed for studying the roles of ITK and BTK in immune cell signaling and for evaluating covalent kinase inhibition as a therapeutic strategy for autoimmune diseases and B cell malignancies. The compound is a covalent inhibitor of ITK and BTK with IC50 values of 2 nM for both kinases. PF-06465469's covalent binding mechanism ensures sustained inhibition of its targets. PF-06465469 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical immunology and oncology research. PF-06465469 is available from various chemical suppliers for research purposes.
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| References |
| Molecular Formula |
C30H33N7O2
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|---|---|
| Molecular Weight |
523.62872
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| Exact Mass |
523.27
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| Elemental Analysis |
C, 68.81; H, 6.35; N, 18.72; O, 6.11
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| CAS # |
1407966-77-1
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| Related CAS # |
1407966-77-1
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| PubChem CID |
71450146
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| Appearance |
White to off-white solid powder
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| LogP |
5.701
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
39
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| Complexity |
883
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(N1CCCC(N2C3=NC=NC(N)=C3C(C3=CC=CC(C(NC4C=C(C)C(C(C)C)=CC=4)=O)=C3)=N2)C1)(=O)C=C
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| InChi Key |
CGJVMKJGKFEHTL-HSZRJFAPSA-N
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| InChi Code |
InChI=1S/C30H33N7O2/c1-5-25(38)36-13-7-10-23(16-36)37-29-26(28(31)32-17-33-29)27(35-37)20-8-6-9-21(15-20)30(39)34-22-11-12-24(18(2)3)19(4)14-22/h5-6,8-9,11-12,14-15,17-18,23H,1,7,10,13,16H2,2-4H3,(H,34,39)(H2,31,32,33)/t23-/m1/s1
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| Chemical Name |
3-[4-amino-1-[(3R)-1-prop-2-enoylpiperidin-3-yl]pyrazolo[3,4-d]pyrimidin-3-yl]-N-(3-methyl-4-propan-2-ylphenyl)benzamide
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| Synonyms |
PF-6465469; PF-06465469; PF 6465469; PF 06465469; PF6465469; PF06465469
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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: ~11 mg/mL (~21.0 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.1 mg/mL (2.10 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 11.0 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: ≥ 1.1 mg/mL (2.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 11.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.1 mg/mL (2.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9097 mL | 9.5487 mL | 19.0975 mL | |
| 5 mM | 0.3819 mL | 1.9097 mL | 3.8195 mL | |
| 10 mM | 0.1910 mL | 0.9549 mL | 1.9097 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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