PF-431396
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 407200

CAS#: 717906-29-1

Description: 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

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PF-431396
CAS# 717906-29-1

Theoretical Analysis

MedKoo Cat#: 407200
Name: PF-431396
CAS#: 717906-29-1
Chemical Formula: C22H21F3N6O3S
Exact Mass: 506.13
Molecular Weight: 506.500
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 Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1650 Ready to ship
1g USD 2950 Ready to ship
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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:

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 39.48

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.

Recalculate based on batch purity %
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: 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.
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.

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1: Chien PT, Lin CC, Hsiao LD, Yang CM. Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes. Toxicol Appl Pharmacol. 2015 Sep 15. pii: S0041-008X(15)30083-1. doi: 10.1016/j.taap.2015.09.009. [Epub ahead of print] PubMed PMID: 26385185.

2: Matsuzawa M, Arai C, Nomura Y, Murata T, Yamakoshi Y, Oida S, Hanada N, Nakamura Y. Periostin of human periodontal ligament fibroblasts promotes migration of human mesenchymal stem cell through the αvβ3 integrin/FAK/PI3K/Akt pathway. J Periodontal Res. 2015 Dec;50(6):855-863. doi: 10.1111/jre.12277. Epub 2015 Apr 20. PubMed PMID: 25900259.

3: Chien PT, Lin CC, Hsiao LD, Yang CM. c-Src/Pyk2/EGFR/PI3K/Akt/CREB-activated pathway contributes to human cardiomyocyte hypertrophy: Role of COX-2 induction. Mol Cell Endocrinol. 2015 Jul 5;409:59-72. doi: 10.1016/j.mce.2015.04.005. Epub 2015 Apr 11. PubMed PMID: 25869400.

4: Hsu CK, Lee IT, Lin CC, Hsiao LD, Yang CM. Sphingosine-1-phosphate mediates COX-2 expression and PGE2 /IL-6 secretion via c-Src-dependent AP-1 activation. J Cell Physiol. 2015 Mar;230(3):702-15. doi: 10.1002/jcp.24795. PubMed PMID: 25201048.

5: Battistone MA, Alvau A, Salicioni AM, Visconti PE, Da Ros VG, Cuasnicú PS. Evidence for the involvement of proline-rich tyrosine kinase 2 in tyrosine phosphorylation downstream of protein kinase A activation during human sperm capacitation. Mol Hum Reprod. 2014 Nov;20(11):1054-66. doi: 10.1093/molehr/gau073. Epub 2014 Sep 1. PubMed PMID: 25180269; PubMed Central PMCID: PMC4209883.

6: Martel-Gallegos G, Casas-Pruneda G, Ortega-Ortega F, Sánchez-Armass S, Olivares-Reyes JA, Diebold B, Pérez-Cornejo P, Arreola J. Oxidative stress induced by P2X7 receptor stimulation in murine macrophages is mediated by c-Src/Pyk2 and ERK1/2. Biochim Biophys Acta. 2013 Oct;1830(10):4650-9. doi: 10.1016/j.bbagen.2013.05.023. Epub 2013 May 24. PubMed PMID: 23711511.