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Linsitinib

Catalog No. T6017 CAS 867160-71-2

Synonyms: OSI-906

OSI-906 (Linsitinib (OSI-906)) is an orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Linsitinib selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGF-1R stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.

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Linsitinib, CAS 867160-71-2

Pack Size	Availability	Price/USD
2 mg	In stock	$ 33.00
5 mg	In stock	$ 52.00
10 mg	In stock	$ 74.00
25 mg	In stock	$ 118.00
50 mg	In stock	$ 168.00
100 mg	In stock	$ 233.00
1 mL * 10 mM (in DMSO)	In stock	$ 58.00

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Purity: 99.8%

Purity: 98.98%

Purity: 98%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	OSI-906 (Linsitinib (OSI-906)) is an orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Linsitinib selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGF-1R stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.
Targets&IC50	IGF-1R:35 nM, Insulin receptor:75 nM, IRR:75 nM
In vitro	OSI-906 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. OSI-906 enables an intermediate conformation of the target protein through interactions with the C-helix. OSI-906 displays favorable metabolic stability in liver microsomes. OSI-906 fully inhibits both IR and IGF-1R phosphorylation at a concentration of 1 μM. OSI-906 inhibits proliferation of several tumor cell lines including non-small-cell lung cancer and colorectal cancer (CRC) tumor cell line with EC50?of 0.021 to 0.810 μM. [1]
In vivo	OSI-906 effectively inhibits tumor growth in IGF-1R-driven xenograft mouse models, achieving 100% tumor growth inhibition (TGI) and 55% regression at a 75 mg/kg dosage, and 60% TGI with no regression at 25 mg/kg. Its elimination half-life varies across species, recorded at 1.18 hours in dogs, 2.64 hours in rats, and 2.14 hours in mice. Additionally, the Vmax of OSI-906 is not dose-proportional when administered in varying single doses to female Sprague-Dawley rats and CD-1 mice. At 25 mg/kg, OSI-906 raises blood glucose levels after 12 days of treatment. A single 75 mg/kg dose in an IGF-1R-driven full-length human IGF-1R (LISN) xenograft mouse model maximizes IGF-1R phosphorylation inhibition (80%) between 4 and 24 hours, correlating with plasma drug concentrations of 26.6-4.77 μM. Furthermore, a 60 mg/kg dose in NCI-H292 xenograft mice diminishes glucose uptake at 2, 4, and 24 hours post-treatment, indicating OSI-906's potent antitumor efficacy in NCI-H292 xenograft mouse models.
Kinase Assay	Protein kinase biochemical assays: Protein kinase assays are either performed in-house by ELISA-based assay methods (IGF-1R,IR,EGFR and KDR) or at Upstate Inc.by a radiometric method with ATP at 100 μM concentration.In-house ELISA assays use poly(Glu:Tyr) as the substrate bound to the surface of 96-well assay plates and phosphorylation is detected using an antiphosphotyrosine antibody conjugated to horseradish peroxidase.The bound antibody is quantified using ABTS as the peroxidase substrate by measuring absorbance at 405 / 490 nm.All assays use purified recombinant kinase catalytic domains.Recombinant enzymes of human IGF-1R or EGFR are expressed as an NH2-terminal glutathione S-transferase fusion protein in insect cells and are purified in house.IC50 values are determined from the sigmoidal dose–response plot of percent inhibition versus log10 compound concentration.A minimum of three measurements,performed in duplicate,are carried out with in-house assays unless otherwise indicated.OSI-906 at a concentration of 1 μM is profiled versus a panel of kinases using the ProfilerProTM Kinase Selectivity Assay Kit.
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)

Synonyms	OSI-906
Molecular Weight	421.49
Formula	C26H23N5O
CAS No.	867160-71-2

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 78 mg/mL (185.1 mM)

References and Literature

1. Mulvihill MJ, et al. Future Med Chem, 2009, 1(6), 1153-1171. 2. McKinley ET, et al. Clin Cancer Res, 2011, 17(10), 3332-3340.

Citations

1. Chen F, Shi Q, Pei F, et al. A systems‐level study reveals host‐targeted repurposable drugs against SARS‐CoV‐2 infection. Molecular Systems Biology. 2021, 17(8): e10239 2. Kang J, Guo Z, Zhang H, et al. Dual Inhibition of EGFR and IGF-1R Signaling Leads to Enhanced Antitumor Efficacy against Esophageal Squamous Cancer. International Journal of Molecular Sciences. 2022, 23(18): 10382 3. Yang N, Fan Z, Sun S, et al.Discovery of highly potent and selective KRASG12C degraders by VHL-recruiting PROTACs for the treatment of tumors with KRASG12C-Mutation.European Journal of Medicinal Chemistry.2023: 115857. 4. Guan J, Borenäs M, Xiong J, et al.IGF1R Contributes to Cell Proliferation in ALK-Mutated Neuroblastoma with Preference for Activating the PI3K-AKT Signaling Pathway.Cancers.2023, 15(17): 4252.

Related compound libraries

This product is contained In the following compound libraries：

Anti-Cancer Drug Library Tyrosine Kinase Inhibitor Library Anti-Cancer Clinical Compound Library Anti-Cancer Active Compound Library Kinase Inhibitor Library Drug Repurposing Compound Library Inhibitor Library Metabolism Compound Library Anti-Lung Cancer Compound Library Endocrinology-Hormone Compound Library

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Keywords

Linsitinib 867160-71-2 Tyrosine Kinase/Adaptors IGF-1R OSI 906 Inhibitor inhibit OSI-906 Insulin Receptor OSI906 inhibitor

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