Linsitinib

SKU: orb1301148

Description

Linsitinib (OSI-906) is a selective, orally active IGF-1R inhibitor with antitumor potential. It suppresses cancer cell proliferation and promotes apoptosis by blocking IGF-1R signaling, a pathway overactive in many cancers. Its activity has been investigated in preclinical in vitro and in vivo studies across various oncology research fields.

Research Area

Signal Transduction

Key Properties

• CAS Number: 867160-71-2
• MW: 421.49
• Purity: >98%
• Formula: C₂₆H₂₃N₅O
• SMILES: NC=1C=2N(C(=NC2C3=CC4=C(C=C3)C=CC(=N4)C5=CC=CC=C5)[C@H]6C[C@@](C)(O)C6)C=CN1
• Target: Kinase
• Solubility: Soluble in DMSO (up to 30 mg/ml).

Bioactivity

• Target IC50:
  Insulin Receptor:75 nM|IGF-1R:35 nM|IRR:75 nM
• In Vivo:
  Linsitinib inhibits tumor growth in an IGF-1R-driven xenograft mouse model, with 100% TGI and 55% regression at a dose of 75 mg/kg and 60% TGI and no regression at a dose of 25 mg/kg.Linsitinib administration induces different elimination half-lives of itself in dog, rat and mice, the elimination half-lives are 1.18 hours, 2.64 hours and 2.14 hours, respectively. Linsitinib administration at different single dose once-daily in femal Sprague-Dawley rat and femal CD-1 mouse reveal that the Vmax is not dose-proportional to Linsitinib dose. Linsitinib elevates the blood glucose levels at a dose of 25 mg/kg after 12 days administration. Linsitinib administration at a single dose of 75 mg/kg in IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model achieve maximal inhibition of IGF-1R phosphorylation (80%) between 4 and 24 hours with plasma drug concentrations of 26.6-4.77 μM. Linsitinib administered as a single dose of at 60 mg/kg in NCI-H292 xenografts mice inhibits uptake of glucose at 2, 4, and 24 hours post-treatment in vivo. Linsitinib inhibits the growth of tumors in NCI-H292 xenograft mouse model.
• In Vitro:
  Linsitinib inhibits IGF-1R autophosphorylation and activation of the downstream signaling proteins Akt, ERK1/2 and S6 kinase with IC50 of 0.028 to 0.13 μM. Linsitinib enables an intermediate conformation of the target protein through interactions with the C-helix. Linsitinib displays favorable metabolic stability in liver microsomes. Linsitinib fully inhibits both IR and IGF-1R phosphorylation at a concentration of 1 μM. Linsitinib inhibits proliferation of several tumor cell lines including non-small-cell lung cancer and colorectal cancer (CRC) tumor cell line with EC50of 0.021 to 0.810 μM.
• Cell Research:
  For assays of cell proliferation, cells are seeded into 96-well plates in appropriate media containing FCS 10% and incubated for 3 days in the presence of OSI-906 at various concentrations. Inhibition of cell growth is determined by luminescent quantitation of intracellular ATP content using CellTiterGlo. Data is presented as a fraction of maximal proliferation, calculated by dividing the cellular density in the presence of varying concentrations of OSI-906 by the cellular density of control cells treated with vehicle (DMSO) only.(Only for Reference)

Storage & Handling

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

Alternative Names

OSI-906

Compound Identifiers

PubChem CID

11640390