PI-273

SKU: orb1309251

Description

PI-273 is a substrate-competitive and specific small-molecule inhibitor of PI4KIIα. It has been shown to inhibit the proliferation of breast cancer cells in vitro, making it a useful research tool for studying phosphatidylinositol signaling in oncology and cell biology.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 925069-34-7
• MW: 381.9
• Purity: 90.00% (May vary between batches)
• Formula: C₁₆H₁₆ClN₃O₂S₂
• SMILES: CCc1c(C)sc(NC(=S)NC(=O)c2ccc(Cl)cc2)c1C(N)=O
• Target: Apoptosis,PI4K
• Solubility: DMSO:0.95 mg/mL (2.49 mM)

Bioactivity

• Target IC50:
  PI4KIIα:0.47 μM
• In Vivo:
  PI-273 (intraperitoneal injection; 25 mg/kg/day; 15 days) significantly reduces tumor volume and weight in MCF-7 xenografts . PI-273 (0.5 mg/kg intravenously or 1.5 mg/kg intragastrically; 0.08-5 hours) has a half-life of 0.411 hours for intravenous administration and 1.321 hours for intragastric administration, with an absolute bioavailability of 5.1% .
  Read more...
• In Vitro:
  PI-273 exhibited the greatest inhibitory effect on PI4KIIα kinase activity (IC50 = 0.47 μmol/L) and suppressed cell proliferation. Surface plasmon resonance and thermal shift assays indicated that PI-273 interacted directly with PI4KIIα. The kinetic analysis identified PI-273 as a reversible competitive inhibitor with respect to the substrate phosphatidylinositol (PI), which contrasted with most other PI kinase inhibitors that bind the ATP binding site. PI-273 reduced PI4P content, cell viability, and AKT signaling in wild-type MCF-7 cells, but not in PI4KIIα knockout MCF-7 cells, indicating that PI-273 is highly selective for PI4KIIα. Mutant analysis revealed the role of palmitoylation insertion in the selectivity of PI-273 for PI4KIIα. In addition, PI-273 treatment retarded cell proliferation by blocking cells in G2-M, inducing cell apoptosis and suppressing colony-forming ability. Importantly, PI-273 significantly inhibited MCF-7 cell-induced breast tumor growth without toxicity. PI-273 is the first substrate-competitive, a subtype-specific inhibitor of PI4KIIα, the use of which will facilitate evaluations of PI4KIIα as a cancer therapeutic target.
  Read more...

Storage & Handling

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

Alternative Names

PI273, PI-273, PI 273, PI4 kinases, PI4K, PI4KIIα, Phosphatidylinositol 4 kinases, Inhibitor, inhibit, Apoptosis

Compound Identifiers

PubChem CID

17168969