ChemicalBook--->CAS DataBase List--->867160-71-2

867160-71-2

867160-71-2 Structure

867160-71-2 Structure
IdentificationBack Directory
[Name]

OSI-906
[CAS]

867160-71-2
[Synonyms]

OSI-906
OSI 906AA
Linsitinib
Linsitinib(OSI906)
OSI-906 Linsitinib
Linsitinib, Free Base
cis-3-[8-Amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol
(1s,3s)-3-(8-amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutanol
Cyclobutanol, 3-[8-aMino-1-(2-phenyl-7-quinolinyl)iMidazo[1,5-a]pyrazin-3-yl]-1-Methyl-, cis-
3-(8-Amino-1-(2-phenylquinolin-7-yl)-2,3-dihydro-imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobuta
(1s,3r)-3-[4-aMino-3-(2-phenylquinolin-7-yl)iMidazo[1,5-a]pyrazin-1-yl]-1-Methylcyclobutan-1-ol
(1S,3r)-3-((S)-8-aMino-1-(2-phenylquinolin-7-yl)-2,3-dihydroiMidazo[1,5-a]pyrazin-3-yl)-1-Methylcyclobutanol
cis-3-[8-Amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol Linsitinib(OSI906)
[EINECS(EC#)]

1533716-785-6
[Molecular Formula]

C26H23N5O
[MDL Number]

MFCD23726651
[MOL File]

867160-71-2.mol
[Molecular Weight]

421.51
Chemical PropertiesBack Directory
[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.
Hazard InformationBack Directory
[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.
[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
Questions And AnswerBack Directory
[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.
Spectrum DetailBack Directory
[Spectrum Detail]

Linsitinib(867160-71-2)1HNMR
867160-71-2 suppliers list
Company Name: Capot Chemical Co.,Ltd.
Tel: +86-(0)57185586718 +86-13336195806 , +86-13336195806
Website: www.capot.com
Company Name: ATK CHEMICAL COMPANY LIMITED
Tel: +undefined-21-51877795
Website: www.atkchemical.com
Company Name: Biochempartner
Tel: 0086-13720134139
Website: www.biochempartner.com
Company Name: Changzhou PBpharmaceutical R&D Co.,Ltd
Tel: 0519-83990708
Website: www.chemicalbook.com/ShowSupplierProductsList31332/0.htm
Company Name: CONIER CHEM AND PHARMA LIMITED
Tel: +8618523575427 , +8618523575427
Website: http://www.conier.com/
Company Name: career henan chemical co
Tel: +86-0371-86658258 +8613203830695 , +8613203830695
Website: www.coreychem.com
Company Name: Dideu Industries Group Limited
Tel: +86-29-89586680 +86-15129568250 , +86-15129568250
Website: https://www.dideu.com
Company Name: Zhejiang J&C Biological Technology Co.,Limited
Tel: +1-2135480471 +1-2135480471 , +1-2135480471
Website: https://www.sarms4muscle.com
Company Name: Henan Alfa Chemical Co., Ltd
Tel: +8615838112936 , +8615838112936
Website: www.chemicalbook.com/manufacturer/henan-alfa-chemical-570/
Company Name: InvivoChem
Tel: +1-708-310-1919 +1-13798911105 , +1-13798911105
Website: https://www.invivochem.com/
Company Name: Huadong Medicine (Xi'an)Bodyguard Pharmaceutical Co.,Ltd.
Tel: +86-029-86185165 +8618629664246 , +8618629664246
Website: www.chemicalbook.com/ShowSupplierProductsList37438/0.htm
Company Name: LEAP CHEM CO., LTD.
Tel: +86-852-30606658
Website: www.leapchem.com
Company Name: Henan Aochuang Chemical Co.,Ltd.
Tel: +86-0371-63689365 +8618638391208 , +8618638391208
Website: http://www.aochuangchem.com/
Company Name: TargetMol Chemicals Inc.
Tel:
Website: www.targetmol.com/
Company Name: ShenZhen Trendseen Biological Technology Co.,Ltd.
Tel: 13417589054 , 13417589054
Website: www.chemicalbook.com/ShowSupplierProductsList1962465/0.htm
Company Name: LEAPCHEM CO., LTD.
Tel: +86-852-30606658
Website: www.leapchem.com
Company Name: Henan Fengda Chemical Co., Ltd
Tel: +86-371-86557731 +86-13613820652 , +86-13613820652
Website: http://www.fdachem.com
Company Name: Shanghai Acmec Biochemical Technology Co., Ltd.
Tel: +86-18621343501; +undefined18621343501 , +undefined18621343501
Website: http://www.acmec.com.cn/
Tags:867160-71-2 Related Product Information
30562-34-6 244240-24-2 149647-78-9 7689-03-4 1025967-78-5 668270-12-0 129830-38-2 1032350-13-2 183319-69-9 942183-80-4 1001350-96-4 763113-22-0

  • HomePage | Member Companies | Advertising | Contact us | Previous WebSite | MSDS | CAS Index | CAS DataBase | Privacy | Terms | About Us
  • All products displayed on this website are only for non-medical purposes such as industrial applications or scientific research, and cannot be used for clinical diagnosis or treatment of humans or animals. They are not medicinal or edible.
    According to relevant laws and regulations and the regulations of this website, units or individuals who purchase hazardous materials should obtain valid qualifications and qualification conditions.
  • Copyright © 2023 ChemicalBook All rights reserved.