PYK2 (proline-rich tyrosine kinase 2) and Pyk2 (proline-rich tyrosine kinase 2) are non-receptor protein tyrosine kinases that are involved in cell proliferation, migration and survival. PF-431396 is a dual inhibitor of both PYK2 and FAK with IC50 values of 11nM and 2nM, respectively. Treatment with PF-431396 ranging in 0.1-1μM on hMSC led to a modest albeit significant increase in day 7 alkaline phosphatase activity[1]. Suppression of Pyk2 and FAK by PF-431396 at concentration of 2.5μM to A20 cells can inhibit B cell spreading induced by BCR/integrin co-stimulation or integrin engagement[2].
作用机制
PF-431396 is an ATP-competitive inhibitor of FAK kinases which can occupy the nucleotide binding pocket, with the pyrimidine ring located in the adenine pocket.[1]
PF-431396 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human pulmonary alveolar epithelial cells (HPAEpiCs)
0.1, 1, 3 µM
1 hour
Inhibited SiNP-induced COX-2 expression
Biomedicines. 2023 Sep 25;11(10):2628.
A20 cells
2.5 µM
1, 2, or 4 hours
PF-431396 treatment significantly reduced the ability of A20 cells to spread on fibronectin, indicating that the kinase activities of Pyk2 and FAK are crucial for B cell spreading.
J Biol Chem. 2009 Aug 21;284(34):22865-77.
MV4-11 cells
300 nM
16 hours
To assess the effect of PF-431396 on the translation rate of proteins in MV4-11 cells, it was found that PF-431396 treatment significantly affected the translation of proteins involved in cell cycle regulation and extracellular matrix organization.
Leukemia. 2022 Oct;36(10):2418-2429.
Gastric fundus smooth muscle cells
0.3 µM
2 minutes
PDBu or calyculin A contracted gastric fundus smooth muscle strips and increased FAK Y397 phosphorylation in a Ca2+-independent manner
J Physiol. 2018 Jun;596(11):2131-2146.
MV4-11 cells
200 nM
24 hours
To assess the effect of PF-431396 on the adhesion of MV4-11 cells, it was found that PF-431396 treatment significantly reduced cell adhesion.
Leukemia. 2022 Oct;36(10):2418-2429.
A375 melanoma cells
1 µM
24 hours
To investigate the effect of PF-431396 on melanoma cell migration and matrix degradation. Results showed that PF-431396 significantly inhibited melanoma cell migration without altering matrix degradation.
Cell Death Dis. 2023 Mar 11;14(3):190.
MG6 cells
1000 nM
24 hours
To assess the effect of Pyk2 inhibition on MG6 cell proliferation, results showed a significant decrease in proliferation at 1000 nM concentration.
J Neuroinflammation. 2024 Aug 6;21(1):196.
HMC3 cells
1000 nM
24 hours
To assess the effect of Pyk2 inhibition on HMC3 cell multinucleation, results showed a significant increase in multinucleation at 1000 nM concentration.
J Neuroinflammation. 2024 Aug 6;21(1):196.
Caco-2 cells
0.25 µM
24 hours
Treatment with PF-43 increased the epithelial barrier function and enhanced mitochondrial respiration levels in Caco-2 cells
Tissue Barriers. 2021 Apr 3;9(2):1890526.
H2596 cells
1 µM
48 hours
Induced apoptosis, a two-fold increase in the number of apoptotic cells in H2596 cell line
Cancer Biol Ther. 2018 Apr 3;19(4):316-327.
MiaPaca 2 cells
1 µM
48 hours
Induced apoptosis, significant increase in the number of apoptotic cells in MiaPaca 2 cells
Cancer Biol Ther. 2018 Apr 3;19(4):316-327.
Capan 1 cells
2 µM and 4 µM
48 hours
Induced apoptosis, significant increase in the number of apoptotic cells in Capan 1 cells
PF-431396 inhibited both phasic and tonic components of the K+-induced contractile response and Pyk2 autophosphorylation, indicating that Pyk2 plays an important role in K+-induced contraction.
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