GDC-0326

SKU: orb1226615

Description

A potent, selective, orally available PI3Kα inhibitor with Ki of 0.2 nM; displays 133, 20 and 33-fold selectivity over PI3Kβ, PI3Kδ and PI3Kγ, respectively; inhibits MCF7-neo/HER2 and PC3 cells proliferation with IC50 of 0.1 uM and 2.2 uM, respectively; reduces tumor growth as well as vascular area in vivo, also reduces the incidence of liver and lymph node metastasis.

Key Properties

• CAS Number: 1282514-88-8
• MW: 382.424
• Purity: >98% (HPLC)
• Formula: C₁₉H₂₂N₆O₃
• SMILES: C[C@H](OC1=CC=C2C3=NC(C4=NC=NN4C(C)C)=CN3CCOC2=C1)C(N)=O
• Target: PI3K
• Solubility: DMSO: 69 mg/mL (180.5 mM); Water: Insoluble （ < 1 mg/ml refers to the product slightly soluble or insoluble )

Bioactivity

• In Vivo:
  GDC-0326 is highly stable in human and rat liver microsomes, and there is a good correlation with In vivo rat clearance. It is found to have consistently low clearance and high oral bioavailability across species tested, enabling significant sustained free drug levels. Daily administration of GDC-0326orally at 0.78, 1.56, 3.25, 6.25, or 12.5 mg/kg results in dose-dependent increase in TGI (73%, 79%, 83%, 101%, and 110%, respectively) and tumor regressions (6 PRs out of 10 animal at 6.25 and 12.5 mg/kg) when compared to vehicle treated mice. Daily administration of GDC-0326 orally at 0.78, 1.56, 3.25, 6.25, or 12.5 mg/kg also results in dose-dependent increase in TGI (73%, 97%, 97%, 122%, and 121%, respectively) in the KPL-4 xenograft model. Notably, maximum efficacy of GDC-0326 is observed at 6.25 mg/kg in the KPL-4 model based on TGI and tumor regressions (9 PRs and 1 CR out of 10 animal treated) when compared to vehicle treated mice. Doses of GDC-0326 up to 12.5 mg/kg are well tolerated based on less than 10% body weight loss (data not shown).
• In Vitro:
  GDC-0326 is highly selective over other kinases. In a panel of 235 kinases, only one is inhibited by > 50% by GDC-0326 when tested at 1 μM. GDC-0326 is not an inhibitor of cytochrome P450 enzymes tested (IC50>10 μM against 3A4, 2C9 1A2, 2C19, 2D6), is highly permeable in MDCK cells and has thermodynamic solubility of 82 μg/mL at pH 7.4.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GDC 0326 | GDC0326

Quick Database Links

Gene Symbol

PI3K