ETP-46321

SKU: orb1296115

Description

ETP-46321 is a potent, orally active small molecule inhibitor targeting PI3Kα and PI3Kδ isoforms with Kis of 2.3 nM and 14.2 nM, respectively. It is a valuable research tool for investigating PI3K signaling in oncology and immunology, supporting both in vitro cellular assays and in vivo pharmacokinetic and efficacy studies.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1252594-99-2
• MW: 473.55
• Purity: 99.47%
• Formula: C₂₀H₂₇N₉O₃S
• SMILES: CS(=O)(=O)N1CCN(Cc2cn3cc(nc(N4CCOCC4)c3n2)-c2cnc(N)nc2)CC1
• Target: PI3K
• Solubility: DMSO:30 mg/mL (63.35 mM)

Bioactivity

• Target IC50:
  PI3Kα (H1047R):2.33 nM (Ki)|PI3Kα (E542K):1.89 nM (Ki)|p110β:170 nM (Ki)|p110α:2.3 nM (Ki)|p110γ:179 nM (Ki)|p110δ:14.2 nM (Ki)|PI3Kα (E542K):1.77 nM (Ki)
• In Vivo:
  ETP-46321 has been chosen for in vivo studies due to its promising pharmacokinetic profile in BALB-C mice, characterized by low in vivo Clearance (0.6 L/h/Kg) and high oral bioavailability (90%). This selection was further justified for a preliminary in vivo evaluation in a lung tumor mouse model influenced by a K-RasG12V oncogenic mutation, where it exhibited notable tumor growth inhibition.
• In Vitro:
  ETP-4632 has been profiled and shown to be a potent PI3K α and δ inhibitor, highly selective versus mTOR and 288 representative kinases. ETP-46321 is also tested against three of the p110α mutant enzymes detected in human cancers (E542K, E545K, and H1047R), being equipotent against these mutants when compared to the wild type protein (Kiapp=2.33, 1.77 and 1.89 nM for PI3Kα-H1047R, PI3Kα-E545K and PI3Kα-E542K, respectively). ETP-46321 inhibits the phosphorylation of AKT in the U2OS cell line (IC50: 8.3 nM).
• Animal Research:
  BALB/C mice are treated daily with ETP-46321 (50 mg/kg, p.o.) for three weeks. Tumor volumes of four mice in each treatment group are measured and compared to the starting volume at the beginning of the 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

ETP 46321, ETP46321, ETP-46321, Inhibitor, inhibit, p110δ, p110γ, p110β, p110α, Phosphoinositide 3-kinase, PI3K, PI3Kα, PI3Kα-E545K, PI3Kα-H1047R, PI3Kα-E542K, PI3Kδ

Compound Identifiers

PubChem CID

46927938