Samotolisib

SKU: orb1300379

Description

Samotolisib (LY3023414) is an orally bioavailable, ATP-competitive inhibitor targeting class I PI3K isoforms, DNA-PK, and mTOR. It has been investigated in preclinical and clinical studies for various solid tumors, including advanced breast and colon cancers, demonstrating research utility in both in vitro and in vivo models.

Research Area

Cell Biology, Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 1386874-06-1
• MW: 406.48
• Purity: 99.61%
• Formula: C₂₃H₂₆N₄O₃
• SMILES: COC(C)Cn1c2c(cnc3ccc(cc23)-c2cncc(c2)C(C)(C)O)n(C)c1=O
• Target: DNA-PK,Autophagy,PI3K,mTOR
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:57 mg/mL (140.23 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.92 mM);DMSO:50 mg/mL (123.01 mM)

Bioactivity

• Target IC50:
  DNA-PK:4.24 nM|PI3Kα:6.07 nM|PI3Kβ:77.6 nM|mTOR:165 nM|PI3Kγ:23.8 nM|PI3Kδ:38 nM
• In Vivo:
  In vivo, Samotolisib demonstrates high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates such as AKT, S6K, S6RP, and 4E-BP1 for 4 to 6 hours, reflecting the drug's half-life of 2 hours. Intermittent target inhibition is sufficient for its antitumor activity. Samotolisib shows time- and dose-dependent target inhibition in vivo. It is currently being evaluated in phase 1 and 2 trials for the treatment of human malignancies.
• In Vitro:
  Samotolisib shows high solubility across a wide pH range. In vitro, inhibition of PI3K/AKT/mTOR signaling by Samotolisib causes G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In cell-based assays, Samotolisib inhibition of PI3K and mTOR is assessed in the PTEN-deficient U87 MG glioblastoma cell line. Samotolisib inhibits the phosphorylation of AKT at position T308 downstream of PI3K at an IC50 of 106 nM. Similarly, Samotolisib inhibits phosphorylation of AKT at position S473 (IC50 = 94.2 nM) by mTORC2 as well as phosphorylation of mTORC1 kinase targets p70S6K (position T389; IC50 =10.6 nM) and 4E-BP1 (positions T37/46; IC50 = 187 nM). The downstream phosphorylation of S6RP at positions pS240/244 (IC50 = 19.1 nM) by p70S6K was inhibited as well, indicating target inhibition along the entire PI3K/AKT/mTOR pathway by Samotolisib.

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

Autophagy, DNA-dependent protein kinase, DNAPK, DNA-PK, class I PI3K isoforms, Mammalian target of Rapamycin, GTPL 8918, GTPL8918, GTPL-8918, Inhibitor, inhibit, mTOR kinase, mTOR, LY 3023414, LY3023414, LY-3023414, PI3K, Phosphoinositide 3-kinase, Samotolisib

Compound Identifiers

PubChem CID

76553587