PF-431396 | CAS#717906-29-1 | FAK & PYK2 inhibitor

MedKoo Cat#: 407200 | Name: PF-431396

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-431396 is a potent and selective focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor (IC50 values are 2 and 11 nM respectively).

Chemical Structure

PF-431396

CAS#717906-29-1

Theoretical Analysis

MedKoo Cat#: 407200

Name: PF-431396

CAS#: 717906-29-1

Chemical Formula: C22H21F3N6O3S

Exact Mass: 506.1348

Molecular Weight: 506.50

Elemental Analysis: C, 52.17; H, 4.18; F, 11.25; N, 16.59; O, 9.48; S, 6.33

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,950.00	Ready to ship

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Related CAS #

No Data

Synonym

PF-431396; PF 431396; PF431396.

IUPAC/Chemical Name

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

InChi Key

POJZIZBONPAWIV-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H21F3N6O3S/c1-31(35(2,33)34)18-6-4-3-5-13(18)11-26-20-16(22(23,24)25)12-27-21(30-20)28-15-7-8-17-14(9-15)10-19(32)29-17/h3-9,12H,10-11H2,1-2H3,(H,29,32)(H2,26,27,28,30)

SMILES Code

CS(=O)(N(C)C1=CC=CC=C1CNC2=NC(NC3=CC4=C(NC(C4)=O)C=C3)=NC=C2C(F)(F)F)=O

Appearance

Beige solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB51209

QC Data

View QC data: current batch, Lot#CRB51209

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PF-431396 is a dual focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) inhibitor, with IC50 values of 2 nM and 11 nM, respectively.

In vitro activity:

To investigate the roles of Pyk2 phosphorylated angulin-1/LSR and TRIC in the intestinal epithelial barrier, 2D and 2.5D cultures of Caco-2 cells were treated with the Pyk2 inhibitor PF-43 with or without HMGB1, inflammatory cytokines TNFα and IFNγ. Treatment with PF-43 increased expression of angulin-1/LSR, phosphorylated AMPK and phosphorylated MAPK and decreased that of phosphorylated JNK, with upregulation of the epithelial barrier and cellular metabolism measured as basal oxygen consumption rate (OCR) and ATP production in 2D culture. Treatment with PF-43 prevented the downregulation of the epithelial barrier by HMGB1 and inflammatory cytokines in 2D culture. Treatment with PF-43 prevented the epithelial hyperpermeability induced by HMGB1 and inflammatory cytokines in 2.5D culture. In 2.5D culture, treatment with PF-43 inhibited the decreases of angulin-1/LSR, TRIC, pJNK, pAMPK and pMAPK induced by HMGB1 and the inflammatory cytokines. Treatment with PF-43 inhibited in part the induced phosphorylation of the serine of angulin-1/LSR and TRIC. Reference: Tissue Barriers. 2021 Apr 3;9(2):1890526. https://www.tandfonline.com/doi/abs/10.1080/21688370.2021.1890526?journalCode=ktib20

In vivo activity:

Excess of glucocorticoids (GCs) is a leading cause of bone fragility, and therapeutic targets are sorely needed. Pharmacological inhibition of proline-rich tyrosine kinase 2 (Pyk2) prevents GC-induced bone loss by overriding GC effects of detachment-induced bone cell apoptosis (anoikis). In wild-type or vehicle-treated mice, GCs either prevented osteoclast apoptosis or promoted osteoblast/osteocyte apoptosis. In contrast, mice treated with Pyk2 kinase inhibitor PF-431396 (PF) were protected. PF-treated mice were also protected from GC-induced bone resorption, microarchitecture deterioration, and weakening of biomechanical properties. Reference: Endocrinology. 2019 Jul 1;160(7):1659-1673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591015/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	20.0	39.48

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 506.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Konno T, Kohno T, Miyakawa M, Tanaka H, Kojima T. Pyk2 inhibitor prevents epithelial hyperpermeability induced by HMGB1 and inflammatory cytokines in Caco-2 cells. Tissue Barriers. 2021 Apr 3;9(2):1890526. doi: 10.1080/21688370.2021.1890526. Epub 2021 Mar 4. PMID: 33660567; PMCID: PMC8078543. 2. Sato AY, Cregor M, McAndrews K, Li T, Condon KW, Plotkin LI, Bellido T. Glucocorticoid-Induced Bone Fragility Is Prevented in Female Mice by Blocking Pyk2/Anoikis Signaling. Endocrinology. 2019 Jul 1;160(7):1659-1673. doi: 10.1210/en.2019-00237. PMID: 31081900; PMCID: PMC6591015.

In vitro protocol:

In vivo protocol:

1. Sato AY, Cregor M, McAndrews K, Li T, Condon KW, Plotkin LI, Bellido T. Glucocorticoid-Induced Bone Fragility Is Prevented in Female Mice by Blocking Pyk2/Anoikis Signaling. Endocrinology. 2019 Jul 1;160(7):1659-1673. doi: 10.1210/en.2019-00237. PMID: 31081900; PMCID: PMC6591015.

1: Lee JW, Mizuno K, Watanabe H, Lee IH, Tsumita T, Hida K, Yawaka Y, Kitagawa Y, Hasebe A, Iimura T, Kong SW. Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute β-amyloid infusion model. J Neuroinflammation. 2024 Aug 6;21(1):196. doi: 10.1186/s12974-024-03192-7. PMID: 39107821; PMCID: PMC11301859. 2: Aida K, Mita M, Ishii-Nozawa R. Difference in Contractile Mechanisms between the Early and Sustained Components of Ionomycin-Induced Contraction in Rat Caudal Arterial Smooth Muscle. Biol Pharm Bull. 2024;47(7):1368-1375. doi: 10.1248/bpb.b24-00297. PMID: 39085076. 3: Lin YJ, Yang CC, Lee IT, Wu WB, Lin CC, Hsiao LD, Yang CM. Reactive Oxygen Species-Dependent Activation of EGFR/Akt/p38 Mitogen-Activated Protein Kinase and JNK1/2/FoxO1 and AP-1 Pathways in Human Pulmonary Alveolar Epithelial Cells Leads to Up-Regulation of COX-2/PGE2 Induced by Silica Nanoparticles. Biomedicines. 2023 Sep 25;11(10):2628. doi: 10.3390/biomedicines11102628. PMID: 37893002; PMCID: PMC10604097. 4: Li X, Ormsby MJ, Fallata G, Meikle LM, Walker D, Xu D, Wall DM. PF-431396 hydrate inhibition of kinase phosphorylation during adherent-invasive Escherichia coli infection inhibits intra-macrophage replication and inflammatory cytokine release. Microbiology (Reading). 2023 Jun;169(6):001337. doi: 10.1099/mic.0.001337. PMID: 37311220; PMCID: PMC10333790. 5: Legrand M, Mousson A, Carl P, Rossé L, Justiniano H, Gies JP, Bouvard D, Sick E, Dujardin D, Rondé P. Protein dynamics at invadopodia control invasion- migration transitions in melanoma cells. Cell Death Dis. 2023 Mar 11;14(3):190. doi: 10.1038/s41419-023-05704-4. PMID: 36899008; PMCID: PMC10006204. 6: Allert C, Waclawiczek A, Zimmermann SMN, Göllner S, Heid D, Janssen M, Renders S, Rohde C, Bauer M, Bruckmann M, Zinz R, Pauli C, Besenbeck B, Wickenhauser C, Trumpp A, Krijgsveld J, Müller-Tidow C, Blank MF. Protein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML. Leukemia. 2022 Oct;36(10):2418-2429. doi: 10.1038/s41375-022-01687-x. Epub 2022 Sep 2. PMID: 36056084; PMCID: PMC9522596. 7: Chen JJ, Zhang LN, Wang HN, Xie CC, Li WY, Gao P, Hu WZ, Zhao ZF, Ji K. FAK inhibitor PF-431396 suppresses IgE-mediated mast cell activation and allergic inflammation in mice. Biochem Pharmacol. 2021 Oct;192:114722. doi: 10.1016/j.bcp.2021.114722. Epub 2021 Aug 9. PMID: 34384759. 8: Konno T, Kohno T, Miyakawa M, Tanaka H, Kojima T. Pyk2 inhibitor prevents epithelial hyperpermeability induced by HMGB1 and inflammatory cytokines in Caco-2 cells. Tissue Barriers. 2021 Apr 3;9(2):1890526. doi: 10.1080/21688370.2021.1890526. Epub 2021 Mar 4. PMID: 33660567; PMCID: PMC8078543. 9: Sato AY, Cregor M, McAndrews K, Li T, Condon KW, Plotkin LI, Bellido T. Glucocorticoid-Induced Bone Fragility Is Prevented in Female Mice by Blocking Pyk2/Anoikis Signaling. Endocrinology. 2019 Jul 1;160(7):1659-1673. doi: 10.1210/en.2019-00237. PMID: 31081900; PMCID: PMC6591015. 10: Tong L, Ao JP, Lu HL, Huang X, Zang JY, Liu SH, Song NN, Huang SQ, Lu C, Chen J, Xu WX. Tyrosine kinase Pyk2 is involved in colonic smooth muscle contraction via the RhoA/ROCK pathway. Physiol Res. 2019 Mar 6;68(1):89-98. doi: 10.33549/physiolres.933857. Epub 2018 Oct 23. PMID: 30433799. 11: Xie Y, Han KH, Grainger N, Li W, Corrigan RD, Perrino BA. A role for focal adhesion kinase in facilitating the contractile responses of murine gastric fundus smooth muscles. J Physiol. 2018 Jun;596(11):2131-2146. doi: 10.1113/JP275406. Epub 2018 Apr 6. PMID: 29528115; PMCID: PMC5983118. 12: Kanteti R, Mirzapoiazova T, Riehm JJ, Dhanasingh I, Mambetsariev B, Wang J, Kulkarni P, Kaushik G, Seshacharyulu P, Ponnusamy MP, Kindler HL, Nasser MW, Batra SK, Salgia R. Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma. Cancer Biol Ther. 2018 Apr 3;19(4):316-327. doi: 10.1080/15384047.2017.1416937. Epub 2018 Feb 22. PMID: 29303405; PMCID: PMC5902231. 13: Zhang K, Yan J, Wang L, Tian X, Zhang T, Guo L, Li B, Wang W, Liu X. The Pyk2/MCU pathway in the rat middle cerebral artery occlusion model of ischemic stroke. Neurosci Res. 2018 Jun;131:52-62. doi: 10.1016/j.neures.2017.09.002. Epub 2017 Sep 12. PMID: 28916471. 14: Zhang Z, Chu SF, Mou Z, Gao Y, Wang ZZ, Wei GN, Chen NH. Ganglioside GQ1b induces dopamine release through the activation of Pyk2. Mol Cell Neurosci. 2016 Mar;71:102-13. doi: 10.1016/j.mcn.2015.12.009. Epub 2015 Dec 17. PMID: 26704905. 15: Mills RD, Mita M, Nakagawa J, Shoji M, Sutherland C, Walsh MP. A role for the tyrosine kinase Pyk2 in depolarization-induced contraction of vascular smooth muscle. J Biol Chem. 2015 Apr 3;290(14):8677-92. doi: 10.1074/jbc.M114.633107. Epub 2015 Feb 24. PMID: 25713079; PMCID: PMC4423659. 16: Yang CM, Lee IT, Hsu RC, Chi PL, Hsiao LD. NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells. Toxicol Appl Pharmacol. 2013 Oct 15;272(2):431-42. doi: 10.1016/j.taap.2013.05.036. Epub 2013 Jun 14. PMID: 23774252. 17: González-Fernández L, Macías-García B, Loux SC, Varner DD, Hinrichs K. Focal adhesion kinases and calcium/calmodulin-dependent protein kinases regulate protein tyrosine phosphorylation in stallion sperm. Biol Reprod. 2013 Jun 6;88(6):138. doi: 10.1095/biolreprod.112.107078. PMID: 23595906. 18: Tse KW, Dang-Lawson M, Lee RL, Vong D, Bulic A, Buckbinder L, Gold MR. B cell receptor-induced phosphorylation of Pyk2 and focal adhesion kinase involves integrins and the Rap GTPases and is required for B cell spreading. J Biol Chem. 2009 Aug 21;284(34):22865-77. doi: 10.1074/jbc.M109.013169. Epub 2009 Jun 26. PMID: 19561089; PMCID: PMC2755694. 19: Han S, Mistry A, Chang JS, Cunningham D, Griffor M, Bonnette PC, Wang H, Chrunyk BA, Aspnes GE, Walker DP, Brosius AD, Buckbinder L. Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG- out) conformation and enables inhibitor design. J Biol Chem. 2009 May 8;284(19):13193-201. doi: 10.1074/jbc.M809038200. Epub 2009 Feb 25. PMID: 19244237; PMCID: PMC2676051.