Pictilisib dimethanesulfonate

SKU: orb1309635

Description

Pictilisib dimethanesulfonate is a potent and selective inhibitor of PI3Kα and PI3Kδ isoforms. It is widely used in preclinical research to investigate PI3K pathway signaling in cancer cell proliferation and tumor growth, with applications in both in vitro and in vivo studies.

Research Area

Cell Biology, Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 957054-33-0
• MW: 705.85
• Purity: 99.69% (May vary between batches)
• Formula: C₂₅H₃₅N₇O₉S₄
• SMILES: CS(O)(=O)=O.CS(O)(=O)=O.CS(=O)(=O)N1CCN(Cc2cc3nc(nc(N4CCOCC4)c3s2)-c2cccc3[nH]ncc23)CC1
• Target: mTOR,DNA-PK,PI3K,Apoptosis,Autophagy
• Solubility: DMSO:50 mg/mL (70.84 mM);H2O:< 0.1 mg/mL (insoluble)

Bioactivity

• Target IC50:
  p110β:33 nM|p110α-H1047R:3 nM|p110α-E545K:3 nM|p110α:3 nM|p110γ:75 nM|mTOR:0.58 μM (Ki)|DNA-PK:1.23 μM|p110δ:3 nM
• In Vivo:
  Pictilisib (GDC-0941)-treated mice display substantial, non-linear tumor shrinkage that reverses upon cessation of treatment, indicating a dependency on continuous administration for sustained efficacy. At doses of 25 or 50 mg/kg, Pictilisib effectively diminishes tumor growth and inhibits the PI3K and HIF-1 pathways in eGFP-FTC133 tumor-bearing mice. Additionally, a higher dose of 150 mg/kg administered orally achieves tumor stasis in MCF7-neo/HER2 model animals. The combination of Pictilisib with RP-56976 facilitates tumor regression and enhances antitumor responses during the treatment regimen, suggesting a synergistic interaction between the two compounds.
• In Vitro:
  Pictilisib (GDC-0941) demonstrates high efficacy in inhibiting cell growth, inducing G0-G1 arrest, and promoting apoptosis, especially when used in combination with U0126. It shows increased sensitivity in H460 cells harboring PIK3CA mutations over A549 cells with wild-type PIK3CA, by diminishing PI3K pathway activity as evidenced by reduced pAK levels. Pictilisib significantly lowers VEGF secretion in the medium following hypoxic/anoxic conditions across all tested cell lines. In breast cancer cell model systems, Pictilisib, alongside RP-56976, considerably decreases tumor cell viability by 80% or more, surpassing the effects of single-agent treatments. It effectively inhibits Akt phosphorylation and affects downstream targets including pPRAS40 and pS6 in various tumor models such as Hs578T1.2 (PI3Kα wild-type), MCF7-neo/HER2 (PI3Kα-mutant), and MX-1 (PTEN-null). Furthermore, Pictilisib reduces the duration of RP-56976-induced mitotic arrest, leading to apoptosis, and exhibits strong antitumor activity against ZD1839-resistant NSCLC cell lines, A549 and H460, highlighting its potential as a therapeutic agent in cancer treatment.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Apoptosis, Autophagy, DNA-PK, DNAPK, mTOR, inhibit, Inhibitor, GDC0941, GDC-0941, GDC-0941 2 MeSO3H, GDC-0941 2 MeSO3H salt, GDC-0941 dimethanesulfonate, GDC 0941, Phosphoinositide 3-kinase, Pictilisib dimethanesulfonate, Pictilisib, PI3K, p110α-E545K, p110α-H1047R, p110α, p110β, p110δ, p110γ

Compound Identifiers

PubChem CID

56972143