Linsitinib
- CAS No.
- 867160-71-2
- Chemical Name:
- Linsitinib
- Synonyms
- OSI-906;CS-190;OSI 906AA;Linsitinib;OSI 906;OSI906;Linsitinib(OSI906);OSI-906 Linsitinib;Linsitinib USP/EP/BP;Linsitinib, Free Base;LINSITINIB;OSI 906; OSI906
- CBNumber:
- CB62501004
- Molecular Formula:
- C26H23N5O
- Molecular Weight:
- 421.49
- MDL Number:
- MFCD12912153
- MOL File:
- 867160-71-2.mol
- MSDS File:
- SDS
Melting point | >175°C (dec.) |
---|---|
Density | 1.39 |
storage temp. | -20°C |
solubility | Soluble in DMSO (up to 30 mg/ml) |
form | solid |
pka | 14.84±0.40(Predicted) |
color | Yellow |
Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months. |
NCI Dictionary of Cancer Terms | OSI-906 |
FDA UNII | 15A52GPT8T |
NCI Drug Dictionary | linsitinib |
SAFETY
Risk and Safety Statements
Symbol(GHS) | GHS07 |
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Signal word | Warning | |||||||||
NFPA 704 |
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Linsitinib price More Price(33)
Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
---|---|---|---|---|---|---|---|
Cayman Chemical | 17708 | Linsitinib ≥98% | 867160-71-2 | 1mg | $40 | 2024-03-01 | Buy |
Cayman Chemical | 17708 | Linsitinib ≥98% | 867160-71-2 | 5mg | $119 | 2024-03-01 | Buy |
Cayman Chemical | 17708 | Linsitinib ≥98% | 867160-71-2 | 10mg | $218 | 2024-03-01 | Buy |
Usbiological | 015629 | Linsitinib | 867160-71-2 | 5mg | $245 | 2021-12-16 | Buy |
TRC | L469020 | Linsitinib | 867160-71-2 | 100mg | $990 | 2021-12-16 | Buy |
Linsitinib Chemical Properties,Uses,Production
Description
Linsitinib (OSI-906) is a selective inhibitor of IGF-1R with IC50 of 35 nM in cell-free assays; modestly potent to InsR with IC50 of 75 nM, and no activity towards Abl, ALK, BTK, EGFR, FGFR1/2, PKA etc. Phase 3.
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.
In vivo
OSI-906 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. OSI-906 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. OSI-906 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 OSI-906 dose. OSI-906 elevates the blood glucose levels at a dose of 25 mg/kg after 12 days administration. OSI-906 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. OSI-906 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. OSI-906 inhibits the growth of tumors in NCI-H292 xenograft mouse model.
Description
The binding of insulin-like growth factor 1 (IGF-1) to the IGF-1 receptor (IGF-1R) promotes cell growth while inhibiting apoptotic pathways. Overexpression of IGF-1R is found in certain solid tumors and hematologic neoplasias. However, insulin receptor (InsR) signaling can compensate for IGF-1R inhibition. Linsitinib is a dual inhibitor of IGF-1R and InsR kinases (IC50s = 35 and 75 nM, respectively). It also inhibits InsR-
Uses
Linsitinib is a small-molecule dual insulin-like growth factor-1 receptor (IGF-IR) and insulin receptor (IR) kinase inhibitor. IGF-I receptor (IGF-IR) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies and thus Linsitinib may be a useful anticancer agent. Potent IGF-1R inhibitor.
Definition
ChEBI: 3-[8-amino-1-(2-phenyl-7-quinolinyl)-3-imidazo[1,5-a]pyrazinyl]-1-methyl-1-cyclobutanol is a member of quinolines and a member of cyclobutanes.
target
IGF-1R
storage
Store at -20°C
References
1) Mulvihill?et al.?(2009),?Discovery of OSI-906: a selective and orally efficacious inhibitor of the IGF-1 receptor and insulin receptor; Future Med. Chem.?1?1153 2) Bendell?et al.?(2015),?A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer; Invest. New Drugs?33?187 3) Pivonello?et al.?(2016),?The dual targeting of insulin and insulin-like growth factor 1 receptor enhances the mTOR inhibitor-mediated antitumor efficacy in hepatocellular carcinoma?; Oncotarget?7?9718 4) Lee?et al.?(2016),?Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells; Mol. Carcinog.?55?991 5) Macaulay?et al.?(2016),?Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors; Clin. Cancer Res.?22?2897 6) De Lint?et al.?(2016),?Sensitizing Triple-Negative Breast Cancer to PI3K Inhibition by Cotargeting IGF1R; Mol. Cancer Ther.?15?1545
Linsitinib Preparation Products And Raw materials
Raw materials
Preparation Products
Supplier | Tel | Country | ProdList | Advantage | |
---|---|---|---|---|---|
Capot Chemical Co.,Ltd. | 571-85586718 +8613336195806 | sales@capotchem.com | China | 29798 | 60 |
Hangzhou FandaChem Co.,Ltd. | 008657128800458; +8615858145714 | fandachem@gmail.com | China | 9285 | 55 |
ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | ivan@atkchemical.com | China | 32836 | 60 |
Biochempartner | 0086-13720134139 | candy@biochempartner.com | CHINA | 967 | 58 |
Changzhou PBpharmaceutical R&D Co.,Ltd | 0519-83990708 | info@pbpharm.com | CHINA | 498 | 58 |
CONIER CHEM AND PHARMA LIMITED | +8618523575427 | sales@conier.com | China | 49392 | 58 |
career henan chemical co | +86-0371-86658258 +8613203830695 | factory@coreychem.com | China | 29821 | 58 |
Dideu Industries Group Limited | +86-29-89586680 +86-15129568250 | 1026@dideu.com | China | 23799 | 58 |
Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 +1-2135480471 | sales@sarms4muscle.com | China | 10522 | 58 |
InvivoChem | +1-708-310-1919 +1-13798911105 | sales@invivochem.cn | United States | 6393 | 58 |
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- Oct 15,2019
View Lastest Price from Linsitinib manufacturers
Image | Update time | Product | Price | Min. Order | Purity | Supply Ability | Manufacturer | |
---|---|---|---|---|---|---|---|---|
2022-10-14 | Linsitinib
867160-71-2
|
US $0.00-0.00 / KG | 1KG | 98% | 1Ton | Henan Aochuang Chemical Co.,Ltd. | ||
2020-01-09 | Linsitinib
867160-71-2
|
US $6.68 / KG | 1KG | 97%-99% | 1kg-1000kg | Career Henan Chemical Co |
- Linsitinib
867160-71-2
- US $0.00-0.00 / KG
- 98%
- Henan Aochuang Chemical Co.,Ltd.
- Linsitinib
867160-71-2
- US $6.68 / KG
- 97%-99%
- Career Henan Chemical Co