Linsitinib
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MedKoo CAT#: 202096

CAS#: 867160-71-2

Description: Linsitinib, also known as OSI-906, is an orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. OSI-906 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, IGFR-1 stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.


Chemical Structure

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Linsitinib
CAS# 867160-71-2

Theoretical Analysis

MedKoo Cat#: 202096
Name: Linsitinib
CAS#: 867160-71-2
Chemical Formula: C26H23N5O
Exact Mass: 421.1903
Molecular Weight: 421.504
Elemental Analysis: C, 74.09; H, 5.50; N, 16.62; O, 3.80

Price and Availability

Size Price Availability Quantity
10.0mg USD 250.0 2 Weeks
25.0mg USD 450.0 2 Weeks
50.0mg USD 700.0 2 Weeks
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Synonym: OSI906; OSI-906; OSI 906; Linsitinib.

IUPAC/Chemical Name: (1r,3r)-3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol.

InChi Key: PKCDDUHJAFVJJB-KQODVJPSSA-N

InChi Code: InChI=1S/C26H23N5O/c1-26(32)14-19(15-26)25-30-22(23-24(27)28-11-12-31(23)25)18-8-7-17-9-10-20(29-21(17)13-18)16-5-3-2-4-6-16/h2-13,19,32H,14-15H2,1H3,(H2,27,28)/t19-,26-

SMILES Code: O[C@@]1(C)C[C@H](C2=NC(C3=CC=C4C=CC(C5=CC=CC=C5)=NC4=C3)=C6C(N)=NC=CN62)C1

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Certificate of Analysis:

Safety Data Sheet (SDS):

Biological target: Linsitinib is a dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC50s of 35 and 75 nM, respectively.
In vitro activity: In cell-based phenotypic assays, OSI-906 inhibited IGF-1- or IGF-2-mediated proliferation (and induced apoptosis, data not shown) in cell lines representing a variety of tumor types. A variety of cell lines were highly sensitive to OSI-906, with EC50 values ranging from 0.021 to 0.810 µM (Table 10). Reference: Future Med Chem. 2009 Sep;1(6):1153-71. https://pubmed.ncbi.nlm.nih.gov/21425998/
In vivo activity: Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by (18)FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers. Daily treatment with 60 mg/kg OSI-906 over 10 days resulted in tumor growth inhibition in the NCI-H292 xenografts compared to controls (Fig. 1A), but no growth changes were observed in the non-responsive NCI-H441 xenografts (Fig. 1B). Reference: Clin Cancer Res. 2011 May 15;17(10):3332-40. https://pubmed.ncbi.nlm.nih.gov/21257723/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 25.0 59.31
DMF:PBS (pH 7.2) (1:30) 0.03 0.07
DMSO 49.04 116.34
Ethanol 1.0 2.37

Preparing Stock Solutions

The following data is based on the product molecular weight 421.504 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Liu L, Liang C, Zhuo C, Jiang H, Ye H, Ruan T, Song J, Jiang S, Zhang Y, Li X. OSI-906 restores the sensitivity of ovarian clear cell carcinoma to cisplatin by targeting the IGF1R/AKT pathway. Med Oncol. 2022 Jan 4;39(2):26. doi: 10.1007/s12032-021-01592-w. PMID: 34982265. 2. Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009 Sep;1(6):1153-71. doi: 10.4155/fmc.09.89. PMID: 21425998. 3. Chai Y, Jia X, Zhu J, Jiang C, Yin N, Li F. Increased Fat Graft Survival By Promoting Adipocyte Dedifferentiation. Aesthet Surg J. 2022 Nov 23:sjac296. doi: 10.1093/asj/sjac296. Epub ahead of print. PMID: 36415951. 4. McKinley ET, Bugaj JE, Zhao P, Guleryuz S, Mantis C, Gokhale PC, Wild R, Manning HC. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40. doi: 10.1158/1078-0432.CCR-10-2274. Epub 2011 Jan 21. PMID: 21257723; PMCID: PMC3122480.
In vitro protocol: 1. Liu L, Liang C, Zhuo C, Jiang H, Ye H, Ruan T, Song J, Jiang S, Zhang Y, Li X. OSI-906 restores the sensitivity of ovarian clear cell carcinoma to cisplatin by targeting the IGF1R/AKT pathway. Med Oncol. 2022 Jan 4;39(2):26. doi: 10.1007/s12032-021-01592-w. PMID: 34982265. 2. Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009 Sep;1(6):1153-71. doi: 10.4155/fmc.09.89. PMID: 21425998.
In vivo protocol: 1. Chai Y, Jia X, Zhu J, Jiang C, Yin N, Li F. Increased Fat Graft Survival By Promoting Adipocyte Dedifferentiation. Aesthet Surg J. 2022 Nov 23:sjac296. doi: 10.1093/asj/sjac296. Epub ahead of print. PMID: 36415951. 2. McKinley ET, Bugaj JE, Zhao P, Guleryuz S, Mantis C, Gokhale PC, Wild R, Manning HC. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40. doi: 10.1158/1078-0432.CCR-10-2274. Epub 2011 Jan 21. PMID: 21257723; PMCID: PMC3122480.

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1: Zhang H, Kathawala RJ, Wang YJ, Zhang YK, Patel A, Shukla S, Robey RW, Talele TT, Ashby CR Jr, Ambudkar SV, Bates SE, Fu LW, Chen ZS. Linsitinib (OSI-906) antagonizes ATP-binding cassette subfamily G member 2 and subfamily C member 10-mediated drug resistance. Int J Biochem Cell Biol. 2014 Jun;51:111-9. doi: 10.1016/j.biocel.2014.03.026. Epub 2014 Apr 12. PubMed PMID: 24726739.

2: Shirakawa J, Okuyama T, Yoshida E, Shimizu M, Horigome Y, Tuno T, Hayasaka M, Abe S, Fuse M, Togashi Y, Terauchi Y. Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β-cell functions, and β-cell proliferation in male mice. Endocrinology. 2014 Jun;155(6):2102-11. doi: 10.1210/en.2013-2032. Epub 2014 Apr 8. PubMed PMID: 24712877.

3: Leiphrakpam PD, Agarwal E, Mathiesen M, Haferbier KL, Brattain MG, Chowdhury S. In vivo analysis of insulin-like growth factor type 1 receptor humanized monoclonal antibody MK-0646 and small molecule kinase inhibitor OSI-906 in colorectal cancer. Oncol Rep. 2014 Jan;31(1):87-94. doi: 10.3892/or.2013.2819. Epub 2013 Oct 25. PubMed PMID: 24173770; PubMed Central PMCID: PMC3868504.

4: Zhao H, Desai V, Wang J, Epstein DM, Miglarese M, Buck E. Epithelial-mesenchymal transition predicts sensitivity to the dual IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines. Mol Cancer Ther. 2012 Feb;11(2):503-13. doi: 10.1158/1535-7163.MCT-11-0327. Epub 2011 Dec 9. PubMed PMID: 22161861.

5: McKinley ET, Bugaj JE, Zhao P, Guleryuz S, Mantis C, Gokhale PC, Wild R, Manning HC. 18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer. Clin Cancer Res. 2011 May 15;17(10):3332-40. doi: 10.1158/1078-0432.CCR-10-2274. Epub 2011 Jan 21. PubMed PMID: 21257723; PubMed Central PMCID: PMC3122480.

6: Mulvihill MJ, Cooke A, Rosenfeld-Franklin M, Buck E, Foreman K, Landfair D, O'Connor M, Pirritt C, Sun Y, Yao Y, Arnold LD, Gibson NW, Ji QS. Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor. Future Med Chem. 2009 Sep;1(6):1153-71. doi: 10.4155/fmc.09.89. PubMed PMID: 21425998.