PP1
This product is for research use only, not for human use. We do not sell to patients.
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| Size | Price | Stock |
|---|---|---|
| 500mg | $799 | Check With Us |
| 1g | $1230 | Check With Us |
| 5g | $3100 | Check With Us |
: Cat #: V0668 CAS #: 172889-26-8 Purity ≥ 98%
Description: PP1 (known also as EI275; EI-275; PP-1; PP 1; AG1872; AG-1872) is a novel, potent and selective Src kinase inhibitor with potential antitumor activity. It inhibits Lck/Fyn kinases with IC50 of 5 nM/6 nM. It exhibits excellent anti-proliferative activity in vitro and high in vivo antitumor efficacy.
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| Molecular Weight (MW) | 281.36 |
|---|---|
| Molecular Formula | C16H19N5 |
| CAS No. | 172889-26-8 |
| Storage | -20℃ for 3 years in powder formr |
| -80℃ for 2 years in solvent | |
| Solubility In Vitro | DMSO: 4 mg/mL (14.2 mM)r |
| Water: <1 mg/mLr | |
| Ethanol: <1 mg/mL | |
| SMILES Code | NC1=C2C(N(C(C)(C)C)N=C2C3=CC=C(C)C=C3)=NC=N1 |
| Synonyms | AGL 1872; EI 275; PP 1; AGL-1872; EI-275; PP-1; AGL1872; EI275; PP1 |
| Protocol | In Vitro | In vitro activity: PP1 is a nano-molar inhibitor of Lck and FynT, inhibits anti-CD3-induced protein-tyrosine kinase activity in T cells (IC50, 0.5 μM), demonstrates selectivity for Lck and FynT over ZAP-70, and preferentially inhibits T cell receptor-dependent anti-CD3-induced T cell proliferation (IC50, 0. 5 μM) over non-T cell receptor-dependent phorbol 12-myristate 13-acetate/interleu-kin-2 (IL-2)-induced T cell proliferation. PP1 (1 μM) selectively inhibits the induction of the IL-2 gene, but not the granulocyte-macrophage colony-stimulating factor or IL-2 receptor genes. PP1 also inhibits Src (IC50, 170 nM) and Hck (IC50, 20 nM). PP1 is 50–100-fold less active in the inhibition of A-431 epidermal growth factor receptor autophosphorylation (IC50, 0.25 μM). PP1 also inhibits Kit and Bcr-Abl tyrosine kinases with IC50 of ∼75 nM and 1 μM, respectively. PP1 completely abrogates the proliferation of M07e cells in response to SCF with IC50 of 0.5–1 μM. PP1 (1 μM) inhibits SCF-induced c-Kit autophosphorylation in intact cells and blocks the activation of mitogen-activated protein kinase and Akt. PP1 inhibits the activity of mutant constitutively active forms of c-Kit (D814V and D814Y) found in mast cell disorders, and triggers apoptosis in the rat basophilic leukemia cell line RBL-2H3 that expresses mutant c-Kit. PP1 reduces the constitutive activation of signal transducer and activators of transcription 5 and mitogen-activated protein kinase and triggeres apoptosis in FDCP1 cells expressing Bcr-Abl. Kinase Assay: Protein A-Sepharose beads (prepared as a 50% (w/v) suspension) are added to the antibody/lysate mixture at 250 μL/mL and allowed to incubate for 30 min at 4°C. The beads are then washed twice in 1 mL of lysis buffer and twice in 1 mL of kinase buffer (25 mM HEPES, 3 mM MnCl2, 5 mM MgCl2, and 100 μM sodium orthovanadate) and resuspended to 50% (w/v) in kinase buffer. Twenty-five microliters of the bead suspension is added to each well of the enolase-coated 96-well high protein binding plate together with an appropriate concentration of compound and [γ-32P]ATP (25 μL/well of a 200 μCi/mL solution in kinase buffer). After incubation for 20 min at 20°C, 60 μL of boiling 2× solubilization buffer containing 10 mM ATP is added to the assay wells to terminate the reactions. Thirty microliters of the samples is removed from the wells, boiled for 5 min, and run on a 7.5% SDS-polyacrylamide gel. The gels are subsequently dried and exposed to Kodak X-AR film. For quantitation, films are scanned using a Molecular Dynamics laser scanner, and the optical density of the major substrate band, enolase p46, is determined. Concentrations of compound that causes 50% inhibition of enolase phosphorylation (IC50) are determined from a plot of the density versus concentration of compound. In companion experiments for measuring the activity of compounds against Lck, the assay plate is washed with two wash cycles on a Skatron harvester using 50 mM EDTA, 1 mM ATP. Scintillation fluid (100 μL) is then added to the wells, and P incorporation is measured using a Pharmacia Biotech micro-β-counter. Concentrations of compound that causes 50% inhibition of enzyme activity (IC50) are determined from a plot of the percent inhibition of enzyme activity versus concentration of compound Cell Assay: Inhibition of anti-CD3-stimulated tyrosine phosphorylation in purified human peripheral blood T cells is measured as follows. All incubations are carried out at 37°C in an Eppendorf Thermomixer 5436 at a mixing setting of 11. Cells (1×106 in 100 μL of RPMI 1640 medium) are incubated for 15 min with drug prior to a 6-min incubation with 1 μg of anti-CD3/mL (anti-leu4, 100 μg/mL). The final volume of the reaction is 115 μL. Reactions are terminated by the addition of 57.5 μL of 3× solubilization buffer incubated at 100°C prior to its addition. Samples are mixed, boiled for 5 min, and stored at -70°C. Western blots of these cell lysates, run on 10% SDS-polyacrylamide gels, are probed with a polyclonal anti-phosphotyrosine antibody, and immune complexes are detected with I-labeled protein A (ICN). For quantitation, films are scanned using a Molecular Dynamics laser scanner, and the optical densities of the major substrate band, p70, are quantitated in the presence of anti-CD3 (in the presence and absence of drug). Percent inhibition is calculated as follows: (1-(p70 optical density units in presence of drug/p70 units in absence of drug))×100. IC50 equals the concentration of compound at which 50% inhibition is measured. |
|---|---|---|
| In Vivo | Under in vivo conditions PP1 was suggested to suppress tyrosine phosphorylation and proliferation in T cells stimulated with anti-CD3 and mitogen. Studies using mice tumor model also showed that PP1 upregulated the expression of the IL-2 gene rather than the granulocyte macrophage colony-stimulating factor or the IL-2 receptor genes. Based on these, PP1 could be adopted as a useful agent to investigate the role of Lck and Fyn T cell activation. |
These protocols are for reference only. InvivoChem does not
independently validate these methods.
| Related Biological Data |
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| Solvent volume to be added | Mass (the weight of a compound) | |||
|---|---|---|---|---|
| Mother liquor concentration | 1mg | 5mg | 10mg | 20mg |
| 1mM | 3.5542 mL | 17.7708 mL | 35.5417 mL | 71.0833 mL |
| 5mM | 0.7108 mL | 3.5542 mL | 7.1083 mL | 14.2167 mL |
| 10mM | 0.3554 mL | 1.7771 mL | 3.5542 mL | 7.1083 mL |
| 20mM | 0.1777 mL | 0.8885 mL | 1.7771 mL | 3.5542 mL |
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