GNE-493

SKU: orb1227101

Description

A potent, selective dual pan-PI3K/mTOR inhibitor with IC50 of 3.4/12/16/16/32 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ/mTOR; displays 100-fold selective for PI3Kα over Aurora A, MLK1, Syk; has good PK profiles, and are efficacious in xenograft models; orally available.

Key Properties

• CAS Number: 1033735-94-2
• MW: 372.4447
• Purity: >98% (HPLC)
• Formula: C₁₇H₂₀N₆O₂S
• SMILES: CC(O)(C1=CC2=NC(C3=CN=C(N)N=C3)=NC(N4CCOCC4)=C2S1)C
• Target: PI3K
• Solubility: DMSO: ≥ 45 mg/mL

Bioactivity

• In Vivo:
  To confirm and compare In vivo efficacy, GNE-493 is examined in the human MCF7.1 breast cancer xenograft model that harbors a PI3Kα activating mutation. Mice bearing xenografts are dosed orally once daily with 10 mg/kg of GNE-493 for 21 continuous days. Similar to observations made in the PC3 prostate cancer xenograft model, 10 mg/kg of GNE-493 results in 73% tumor growth inhibition at day 21 when compared to vehicle control animals. When achieving comparable levels of drug exposure, GNE-493 shows a similar suppression of the PI3K pathway and consequently, a similar efficacy profile against MCF7.1 breast tumors.
• In Vitro:
  GNE-493 is a low molecular weight, potent dual inhibitor of pan-PI3 kinases and mTOR. GNE-493 displays approximately equipotent inhibition of Class I PI3K isoforms, is submitted for screening in a 142 kinase panel provided by Invitrogen’s SelectScreen service. Of these kinases, only three are subject to greater than 50% inhibition by GNE-493, and none are inhibited greater than 80% when tested at 1 μM. Subsequently measured IC50s demonstrated that GNE-493 is more than 100-fold selective for PI3Kα over these three unrelated kinases (Aurora A IC50>10 μM, MLK1 IC50 = 591 nM and SYK IC50 = 371 nM).

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

GNE493 | GNE 493

Quick Database Links

Gene Symbol

PI3K