Antibodies
PF-562271 HCl
- 貨號 Cat. No.
- S7357
- 規格 Size
- 5mgã€50 mg
- 品牌 Brand
- Selleckchem
Description
PF-562271 HCl
Catalog No.S7357
PF-562271 HCl is the hydrochloride salt of PF-562271, which is a potent, ATP-competitive, reversible inhibitor of FAK with IC50 of 1.5 nM, ~10-fold less potent for Pyk2 than FAK and >100-fold selectivity against other protein kinases, except for some CDKs. Phase 1.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | PF-562271 HCl is the hydrochloride salt of PF-562271, which is a potent, ATP-competitive, reversible inhibitor ofFAK with IC50 of 1.5 nM, ~10-fold less potent for Pyk2 than FAK and >100-fold selectivity against other protein kinases, except for some CDKs. Phase 1. | |||||
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| Targets | FAK | Pyk2 | ||||
| IC50 | 1.5 nM | 14 nM [1] | ||||
| In vitro | PF-562271 binds in the ATP-binding cleft of FAK, forming two of the three “canonical” H-bonds between the inhibitor and main-chain atoms in the kinase hinge region. PF-562271 is potent in an inducible cell-based assay measuring phospho-FAK with IC50 of 5 nM. PF-562271 (3.3 μM) results in G1 arrest of PC3-M cells. [1]PF-562271 (1 nM) blocks bFGF-stimulated blood vessel angiogenesis as performed in chicken chorioallantoic membrane assays. PF-262271 potently blocks blood vessel sprouting without detectable changes in vascular leakage. [2] PF-562271 (250 nM) results in complete inhibition of collective A431 cell invasion into collagen gels. [3] | |||||
| In vivo | PF-562271 (< 33 mg/kg p.o.) inhibits FAK phosphorylation in tumors in a dose- and time-dependent manner in U87MG-bearing mice. PF-562271 (50 mg/kg p.o. bid) results in 86% tumor growth inhibition in BxPc3 xenografts mice and 45% tumor growth inhibition in PC3-M xenografts mice. PF-562271 (25 mg/kg, bid) results in 2-fold greater apoptosis in treated tumors in mice bearing H125 lung xenografts. [1] PF-562271 (33 mg/kg, p.o.) inhibits extensive movement of the tumor cells over 24 hours in mice. PF-562271 (33 mg/kg, p.o.) results in altered E-cadherin dynamics in mice, which correlates with reduced E-cadherin–dependent collective cell movement. [3] PF-562271 (25 mg/kg, p.o. bid) results in 62% tumor growth inhibition in PC3M-luc-C6 subcutaneuous local implant xenograft mouse model. [4] PF-562,271 (5 mg/kg, oral) results in significant and similar increases in osteocalcin and cancellous bone parameters and a decrease in tumor growth and signs of bone healing in rats implanted with MDA-MB-231 cells in the tibia. [5] | |||||
| Features | Dual FAK/Pyk2 inhibitor that has been tested in Phase I clinical trials for treatment of pancreatic, head and neck, and prostate cancers. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Recombinant kinase assay | Purified-activated FAK kinase domain (410–689 aa) is reacted with 50 μM ATP and 10 μg per well of a random peptide polymer of Glu and Tyr, p(Glu/Tyr), in kinase buffer [50 mM HEPES (pH 7.5), 125 mM NaCl, and 48 mM MgCl2 for 15 min. Phosphorylation of p(Glu/Tyr) is challenged with serially diluted compound at 1/2-Log concentrations starting at a top concentration of 1 μM. Each concentration is tested in triplicate. Phosphorylation of p(Glu/Tyr) is detected with a general antiphospho-tyrosine (PY20) antibody followed by horseradish peroxidase (HRP)-conjugated goat anti-mouse IgG antibody. HRP substrate is added, and absorbance readings at 450 nm are obtained after addition of stop solution (2 mol/L H2SO4). IC50 values are determined using the Hill-Slope Model. |
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Animal Study: [1]
| Animal Models | Athymic female mice bearing BxPc3 or PC3-M xenografts. |
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| Dosages | 50 mg/kg |
| Administration | Oral gavage |
References
Chemical Information
| Molecular Weight (MW) | 543.95 |
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| Formula | C21H21ClF3N7O3S |
| CAS No. |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 100 mg/mL (183 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | N-Methyl-N-{3-[({2-[(2-oxo-2,3-dihydro-1H-indol-5-yl)amino]-5-(trifluoromethyl)-4-pyrimidinyl}amino)methyl]-2-pyridinyl}methanesulfonamide hydrochloride (1:1) |
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