PF-07245303
PF-07245303 is a ITK/TRK inhibitor. PF-07245303 reduces the production of inflammatory cytokines such as IL-4 and IFNγ, and inhibits the phosphorylation of PLCγ1. PF-07245303 inhibits nerve growth factor-induced basophil activation and the phosphorylation of TRKA. PF-07245303 reduces oxazolone-induced ear swelling in mouse ear tissues. PF-07245303 is applicable to research related to atopic dermatitis.
For research use only. We do not sell to patients.
- CAS No.: 2655556-75-3
- Formula: C25H32N6O2
- Molecular Weight:448.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Help & FAQs
Biological Activity
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TrkA 2.94 nM (Kd) |
TrkB 8.76 nM (Kd) |
TrkC 10 nM (Kd) |
PF-07245303 (0.49-40 nM; 60 s association phase, 60-480 s dissociation phase) binds potently to recombinant human ITK, TRKA, TRKB and TRKC proteins, with Kd values of 0.71 nM, 2.94 nM, 8.73 nM and 10 nM, respectively[1].
PF-07245303 potently inhibits the enzymatic activity of full-length human ITK protein under the condition of 1 mM ATP, with an IC50 of 5.62 nM[1].
PF-07245303 (0-10 μM; 30 min pre-incubation, 5 min activation) potently inhibits ITK-dependent PLCγ1 phosphorylation in Jurkat T cells activated by anti-CD3/CD28, with an IC50 of 154 nM[1].
PF-07245303 potently inhibits IL-2 release from human primary CD4+ T cells activated by anti-CD3/CD28, with an IC50 of 38.5 nM[1].
PF-07245303 inhibits IL-2 release from human whole blood T cells activated by anti-CD3/CD28/CD2, with an IC50 of 1350 nM (122 nM after protein binding correction)[1].
PF-07245303 (20-24 h) inhibits the release of IL-4, IL-13, IFNγ, IL-17A and IL-10 from human primary CD4+ T cells activated by anti-CD3/CD28, with corresponding IC50 values of 73.5 nM, 348 nM, 73.2 nM, 282 nM and 114.5 nM[1].
PF-07245303 (6-7 days) inhibits cytokine release from differentiated human Th1, Th2 and Th17 cells, with IC50 values of 35.4 nM, 60.9 nM and 12.5 nM against IFNγ, IL-13 and IL-17A, respectively[1].
PF-07245303 potently inhibits IFNγ release from human primary CD8+ T cells activated by anti-CD3/CD28, with an IC50 of 18.9 nM[1].
PF-07245303 potently inhibits the enzymatic activities of the cytoplasmic domains of human TRKA, TRKB and TRKC, with mean IC50 values of 7.2 nM, 12.0 nM and 20.7 nM, respectively, under 1 mM ATP conditions[1].
PF-07245303 inhibits ligand-induced phosphorylation of human TRKA, TRKB and TRKC in U2OS cells (expressing p75), with IC50 values of 72.6 nM, 48.7 nM and 21.7 nM, respectively[1].
PF-07245303 inhibits NGF-induced activation of primary human blood basophils with an IC50 of 442 nM (39.8 nM after protein binding correction)[1].
PF-07245303 (0.1-10 μM; 24 h IL-4/IL-13 pre-treatment, 5 min NGF co-incubation) inhibits NGF-induced TRKA phosphorylation in human skin explants pre-treated with IL-4/IL-13[1].
PF-07245303 (0.3-10 μM; 24 h) inhibits anti-CD3/CD28-induced IFNG, IL13 and IL2 mRNA expression in a concentration-dependent manner, with almost complete inhibition observed at 10 μM; meanwhile, this agent also suppresses IL-2 protein release, with significant inhibitory effects detected at 1, 3 and 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat T cells (Clone E6-1)
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Concentration:0, 0.001, 0.003, 0.01, 0.03, 0.1, 1, 3.2, 10 μM
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Incubation Time:30 min (pre-incubation); 5 min (activation)
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Result:Inhibited anti-CD3/CD28-induced phosphorylation of PLCγ1 in a concentration-dependent manner, with an IC50 of 154 nM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 8-10 weeks of age, oxazolone-induced contact hypersensitivity model)[1]
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Dosage:2%
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Administration:topical; daily; starting one hour after the first oxazolone challenge, On days 4, 7, 9, and 11 after the start of oxazolone stimulation
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Result:Inhibited oxazolone-induced ear thickness by 43% - 61% at days 4, 7, 9, and 11 after initiation of challenge.
Reduced visual and histological composite disease scores relative to vehicle treatment.
Moderately decreased ear tissue protein levels of IL-4, IL-10, IL-17A, GM-CSF, and TNFα.
Showed no difference in ear tissue protein levels of IL-2 and IFNγ compared to vehicle.
Moderately decreased scores for dermal inflammatory cell infiltrates and epithelial endpoints including hyperplasia, ulceration, thinning, and surface hyperkeratosis.
Chemical Information
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CAS No. 2655556-75-3
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Molecular Weight 448.56
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Formula C25H32N6O2
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SMILES
CC1=C(C=C2NC(C3=NNC4=C3C[C@@H]5C[C@@]5(C4)C)=NC2=C1)N(C([C@@H](N6CCOCC6)C)=O)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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