WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406126
CAS#: 869288-64-2
Description: PF-573228 is a potent and selective inhibitor of focal adhesion kinase (FAK) (IC50= 4 nM). Displays 50 - 250-fold selectivity for FAK over other protein kinases. PF573228 was recognized to affect cell adhesion and migration in many types of cells.
MedKoo Cat#: 406126
Name: PF-573228
CAS#: 869288-64-2
Chemical Formula: C22H20F3N5O3S
Exact Mass: 491.12389
Molecular Weight: 491.49
Elemental Analysis: C, 53.76; H, 4.10; F, 11.60; N, 14.25; O, 9.77; S, 6.52
Synonym: PF573228; PF 573228; PF-573228; PF573,228; PF 573,228; PF-573,228.
IUPAC/Chemical Name: 3,4-Dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2(1H)-quinolinone
InChi Key: HESLKTSGTIBHJU-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H20F3N5O3S/c1-34(32,33)16-4-2-3-13(9-16)11-26-20-17(22(23,24)25)12-27-21(30-20)28-15-6-7-18-14(10-15)5-8-19(31)29-18/h2-4,6-7,9-10,12H,5,8,11H2,1H3,(H,29,31)(H2,26,27,28,30)
SMILES Code: O=C1NC2=C(C=C(NC3=NC=C(C(F)(F)F)C(NCC4=CC=CC(S(=O)(C)=O)=C4)=N3)C=C2)CC1
Appearance: White 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
| Biological target: | PF-573228 is a potent and selective FAK inhibitor with IC50 of 4 nM (FAK). |
| In vitro activity: | In the present study, the pharmacological effect of PF-573228 on inhibiting FAK activity and limiting lung cancer cell growth was tested. Given the role of FAK signaling in tumor growth and metastasis, it was hypothesized that inhibiting the catalytic activity of FAK may disrupt FAK signaling and blunt tumor cell proliferation. Therefore, three distinct non-small cell lung cancer cell lines (A549 lung adenocarcinoma cells and H460 and H1299 large cell carcinoma cells) were treated with PF-573228, an enzymatic inhibitor of FAK. PF-573228 was administered to the lung cancer cells for 4 days at three doses: 0.1, 1, or 10 μM. The growth curves showed that 10 μM PF-573228 effectively induced cessation of cell growth (Figures 1A–C). When lung cancer cells were treated with PF-573228, an abnormal nuclear shape was observed. Furthermore, it was found that PF-573228 treatment does not dramatically affect nuclear translocation of FAK in A549 cells. This implied that FAK-mediated signaling to maintain lamin A/C expression may not be through transcriptional regulation. Reference: Front Oncol. 2019; 9: 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363943/ |
| In vivo activity: | To better understand the role of FAK in leukocyte recruitment, a FAK-specific inhibitor (PF-573228) was used and determined the effect on IL-4 induced eosinophil recruitment in vitro and in vivo. PF-572338 also prevented IL-4-induced VCAM-1 expression in vivo. Using brightfield intravital microscopy, it was found that PF-573228 decreased leukocyte rolling flux, adhesion, and emigration. Eosinophil recruitment was examined in vivo by using an eosinophil-GFP reporter mouse and found PF-573228 attenuated eosinophil emigration. This study reveals that a FAK inhibitor influences inflammation through its action on eosinophil recruitment. Reference: J Leukoc Biol. 2018 Jul;104(1):147-158. https://pubmed.ncbi.nlm.nih.gov/29633338/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.0 | 40.7 |
The following data is based on the product molecular weight 491.49 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. Chi Q, Wang L, Xie D, Wang X. Characterization of in vitro metabolism of focal adhesion kinase inhibitors by LC/MS/MS. J Pharm Biomed Anal. 2019 May 10;168:163-173. doi: 10.1016/j.jpba.2019.02.028. Epub 2019 Feb 19. PMID: 30807921. 2. Chuang HH, Wang PH, Niu SW, Zhen YY, Huang MS, Hsiao M, Yang CJ. Inhibition of FAK Signaling Elicits Lamin A/CAssociated Nuclear Deformity and Cellular Senescence. Front Oncol. 2019 Jan 30;9:22. doi: 10.3389/fonc.2019.00022. PMID: 30761269; PMCID: PMC6363943. 3. Aulakh GK, Petri B, Wojcik KM, Colarusso P, Lee JJ, Patel KD. Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo. J Leukoc Biol. 2018 Jul;104(1):147-158. doi: 10.1002/JLB.3MA1117-429R. Epub 2018 Apr 6. PMID: 29633338. |
| In vitro protocol: | 1. Chi Q, Wang L, Xie D, Wang X. Characterization of in vitro metabolism of focal adhesion kinase inhibitors by LC/MS/MS. J Pharm Biomed Anal. 2019 May 10;168:163-173. doi: 10.1016/j.jpba.2019.02.028. Epub 2019 Feb 19. PMID: 30807921. 2. Chuang HH, Wang PH, Niu SW, Zhen YY, Huang MS, Hsiao M, Yang CJ. Inhibition of FAK Signaling Elicits Lamin A/CAssociated Nuclear Deformity and Cellular Senescence. Front Oncol. 2019 Jan 30;9:22. doi: 10.3389/fonc.2019.00022. PMID: 30761269; PMCID: PMC6363943. |
| In vivo protocol: | 1. Aulakh GK, Petri B, Wojcik KM, Colarusso P, Lee JJ, Patel KD. Inhibiting focal adhesion kinase (FAK) blocks IL-4 induced VCAM-1 expression and eosinophil recruitment in vitro and in vivo. J Leukoc Biol. 2018 Jul;104(1):147-158. doi: 10.1002/JLB.3MA1117-429R. Epub 2018 Apr 6. PMID: 29633338. |
1: Melo TG, Tucci AR, Nogueira AR, Meirelles Mde N, Pereira MC. The involvement of FAK and Src in the invasion of cardiomyocytes by Trypanosoma cruzi. Exp Parasitol. 2014 Apr;139:49-57. doi: 10.1016/j.exppara.2014.02.008. Epub 2014 Feb 25. PubMed PMID: 24582948.
2: Xu B, Ju Y, Song G. Role of p38, ERK1/2, focal adhesion kinase, RhoA/ROCK and cytoskeleton in the adipogenesis of human mesenchymal stem cells. J Biosci Bioeng. 2014 May;117(5):624-31. doi: 10.1016/j.jbiosc.2013.10.018. Epub 2013 Dec 9. PubMed PMID: 24331979.
3: Beauséjour M, Thibodeau S, Demers MJ, Bouchard V, Gauthier R, Beaulieu JF, Vachon PH. Suppression of anoikis in human intestinal epithelial cells: differentiation state-selective roles of α2β1, α3β1, α5β1, and α6β4 integrins. BMC Cell Biol. 2013 Dec 1;14:53. doi: 10.1186/1471-2121-14-53. PubMed PMID: 24289209.
4: Chan D, Thomas CJ, Taylor VJ, Burke RD. Integrins on eggs: focal adhesion kinase is activated at fertilization, forms a complex with integrins, and is necessary for cortex formation and cell cycle initiation. Mol Biol Cell. 2013 Nov;24(21):3472-81. doi: 10.1091/mbc.E13-03-0148. Epub 2013 Aug 28. PubMed PMID: 23985318; PubMed Central PMCID: PMC3814141.
5: Wiemer AJ, Wernimont SA, Cung TD, Bennin DA, Beggs HE, Huttenlocher A. The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ T cell activation. Biochem Pharmacol. 2013 Sep 15;86(6):770-81. doi: 10.1016/j.bcp.2013.07.024. Epub 2013 Aug 5. PubMed PMID: 23928188; PubMed Central PMCID: PMC3762933.
6: Kline ER, Shupe J, Gilbert-Ross M, Zhou W, Marcus AI. LKB1 represses focal adhesion kinase (FAK) signaling via a FAK-LKB1 complex to regulate FAK site maturation and directional persistence. J Biol Chem. 2013 Jun 14;288(24):17663-74. doi: 10.1074/jbc.M112.444620. Epub 2013 May 1. PubMed PMID: 23637231; PubMed Central PMCID: PMC3682567.
7: Moore SW, Zhang X, Lynch CD, Sheetz MP. Netrin-1 attracts axons through FAK-dependent mechanotransduction. J Neurosci. 2012 Aug 22;32(34):11574-85. doi: 10.1523/JNEUROSCI.0999-12.2012. PubMed PMID: 22915102; PubMed Central PMCID: PMC3461192.
8: Hori Y, Kashimoto T, Yonezawa T, Sano N, Saitoh R, Igarashi S, Chikazawa S, Kanai K, Hoshi F, Itoh N, Higuchi S. Matrix metalloproteinase-2 stimulates collagen-I expression through phosphorylation of focal adhesion kinase in rat cardiac fibroblasts. Am J Physiol Cell Physiol. 2012 Nov 1;303(9):C947-53. doi: 10.1152/ajpcell.00401.2011. Epub 2012 Aug 22. PubMed PMID: 22914642.
9: Tse KW, Lin KB, Dang-Lawson M, Guzman-Perez A, Aspnes GE, Buckbinder L, Gold MR. Small molecule inhibitors of the Pyk2 and FAK kinases modulate chemoattractant-induced migration, adhesion and Akt activation in follicular and marginal zone B cells. Cell Immunol. 2012 Jan-Feb;275(1-2):47-54. doi: 10.1016/j.cellimm.2012.03.002. Epub 2012 Mar 29. PubMed PMID: 22507871.
10: Guessous F, Yang Y, Johnson E, Marcinkiewicz L, Smith M, Zhang Y, Kofman A, Schiff D, Christensen J, Abounader R. Cooperation between c-Met and focal adhesion kinase family members in medulloblastoma and implications for therapy. Mol Cancer Ther. 2012 Feb;11(2):288-97. doi: 10.1158/1535-7163.MCT-11-0490. Epub 2011 Dec 21. PubMed PMID: 22188814; PubMed Central PMCID: PMC3277676.
