PP2

SKU: orb1300922

Description

PP2 is a potent and selective inhibitor of the Src-family kinases Lck and Fyn, with IC50 values of 4 nM and 5 nM, respectively. It exhibits over 100-fold selectivity against EGFR and is inactive against ZAP-70, PKA, and JAK2. This compound is widely used in vitro to investigate T-cell receptor signaling and immune cell activation pathways.

Research Area

Cardiovascular Research, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 172889-27-9
• MW: 301.78
• Purity: >98%
• Formula: C₁₅H₁₆ClN₅
• SMILES: NC1=C2C(=NN(C(C)(C)C)C2=NC=N1)C3=CC=C(Cl)C=C3
• Target: Kinase
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 3 mg/ml with warming).

Bioactivity

• Target IC50:
  Lck:4 nM|Fyn:5 nM
• In Vivo:
  PP2, at concentrations of 1-100 mM, dose-dependently inhibits the growth of the human colon (SW480, HT29, and PMCO1), liver (KYN-2, Li7, PLC/PRF/5, and HepG2), and breast (MDA-MB-468, MCF-7, and BT-474) cancer cells. At 5 µM concentration, PP2 suppresses the phosphorylation and signaling of RET/PTC1 oncoprotein in lysis of NIH3T3 and NIH-RET/PTC3 cells. Additionally, 5 µM PP2 inhibits serum-independent growth in transformed NIH3T3 fibroblasts, and human papillary thyroid carcinoma cell lines TPC1 and FB2 with spontaneous RET/PTC1 rearrangements, as well as hampers Type I collagen matrix invasion by TPC1 cells. At 10 µM, PP2 downregulates the expression levels of pSrc-Y416, pEGFR-Y845, and pEGFR-Y1173 in HeLa and SiHa cells, and regulates cell cycle arrest by upregulating p21(Cip1) and p27(Kip1), and downregulating cyclin A, cyclin-dependent kinases-2 and -4 (Cdk-2, -4) in HeLa cells, and cyclin B and Cdk-2 in SiHa cells. A 20 μM concentration of PP2 inhibits 40-50% of HT29 cell growth within an hour, reduces Src activity maintaining 35% inhibition for two days, and significantly promotes aggregation in most cancer cell lines (HT29, SW480, PMCO1, PLC/PRF/5, KYN-2, Li7, MCF-7, and MDA-MB-468) in an E-cadherin-dependent manner. In cancer cells, 20 μM PP2 boosts E-cadherin expression and its association with the actin cytoskeleton, as well as enhances α-catenin, β-catenin, and γ-catenin expression in HT29 cells, while in PLC/PRF/5 and MCF-7 cells, α-catenin protein levels remain unchanged, and β-catenin and γ-catenin levels slightly increase.
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• In Vitro:
  In rats with focal cerebral ischemic damage, PP2 reduces the infarct area by approximately 50%. Compared to the control group, PP2 (1.5 mg/kg, i.p.) significantly improves neurological function scores in rats with this condition. Additionally, in SCID mice implanted with HT29 cells in the spleen, PP2 (5 mg/kg/day) not only decreases the primary tumor growth rate but also significantly reduces relative liver weight and the amount of liver metastasis, compared to the control group.
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• Cell Research:
  Cell viability is determined using an in vitro toxicology assay kit following the manufacturer's instructions. Cells are seeded in 96-well plates at day 0. Starting at day 1, cells are treated for 2 days with each of a series of increasing concentrations of PP2 (1 μM, 10 μM, and 100 μM). At the end of this period, cell proliferation is evaluated by a colorimetric assay based on the cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide by mitochondria dehydrogenase in viable cells, leading to formazan formation. This experiment is repeated three times with 10 determinations/tested concentration.(Only for Reference)
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Storage & Handling

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

Alternative Names

AGL 1879, AGL1879, AGL-1879, AG 1879, AG 1879,AGL1879, AG 1879,AGL-1879, Lck, Fyn, EGFR, JAK2, ZAP70, Src, PP2, PP-2, PP 2, Tyrosine Kinases, TyrosineKinases

Compound Identifiers

PubChem CID

4878