N-Methyl-N-[2-[[[2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-trifluoromethylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide

Description

Proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK) are nonreceptor tyrosine kinases that constitute the focal adhesion kinase subfamily. PYK2 is expressed in both bone-forming osteoblasts and bone-resorbing osteoclasts where it has a positive role in osteoclast maturation and bone resorption. PF-431396 is a pyrimidine-based dual inhibitor of FAK and PYK2 (IC₅₀s = 2 and 11 nM, respectively). In ovariectomized rats, it has been shown to increase bone formation, promoting osteoblast recruitment and activity.

Uses

PF 431396 is a dual focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor (IC50 values are 2 and 11 nM respectively). Promotes osteoblast recruitment and activity, and stimulates bone formation in ovariectomized rats.

Uses

PF-431396 hydrate has been used as a dual inhibitor of proline-rich tyrosine kinase 2 (PYK2) / focal adhesion kinase (FAK) inhibitor to study its effects on phosphorylation of Yes-associated protein (YAP) at Ser127 and steady state of transcriptional coactivator with PDZ-binding motif (TAZ) . It has also been used as a PYK2/FAK inhibitor to study its effects on protein kinase A activation in human sperm samples .

Definition

ChEBI: N-methyl-N-[2-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]methyl]phenyl]methanesulfonamide is a sulfonamide.

Biochem/physiol Actions

PF-431396 is a potent inhibitor of PYK2 and FAK kinases (IC50 = 11 and 1.5 nM, respectively). PF-431396 increases bone formation and protects against bone loss in ovariectomized rats.

storage

Store at +4°C

References

[1] SEUNGIL HAN. Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design.[J]. The Journal of Biological Chemistry, 2009, 284 19: 13193-13201. DOI: 10.1074/jbc.m809038200
[2] LEONARD BUCKBINDER. Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone formation, and offers an anabolic treatment approach for osteoporosis.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 25: 10619-10624. DOI: 10.1073/pnas.0701421104