PP1

SKU: orb1300990

Description

PP1 (AGL 1872) is a potent and selective Src family kinase inhibitor, exhibiting IC50 values of 5 nM for Lck and 6 nM for Fyn. This cell-permeable compound is widely used in biochemical and cellular research to investigate T-cell receptor signaling and oncogenic pathways in both in vitro and in vivo models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 172889-26-8
• MW: 281.63
• Purity: >98%
• Formula: C₁₆H₁₉N₅
• SMILES: NC1=C2C(=NN(C(C)(C)C)C2=NC=N1)C3=CC=C(C)C=C3
• Target: Kinase
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 10 mg/ml).

Bioactivity

• Target IC50:
  Fyn:6 nM|Lck:5 nM
• In Vitro:
  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.
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• Cell Research:
  PP1 is dissolved in DMSO and stored, and then diluted with appropriate medium before use. 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.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

cKit, Apoptosis, Bcr-Abl, BcrAbl, AGL1872, AGL-1872, AGL 1872, Lck, Inhibitor, EI 275, EI275, EI-275, EGFR, Fyn, inhibit, Kit, Src, PP 1, PP1, PP-1

Compound Identifiers

PubChem CID

1400