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Chemical Structure| 867160-71-2 Chemical Structure| 867160-71-2

Structure of Linsitinib
CAS No.: 867160-71-2

Chemical Structure| 867160-71-2

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Linsitinib (OSI-906) is a potent, selective, and orally bioavailable dual inhibitor of the IGF-1 receptor and insulin receptor (IR) with IC50s of 35 nM and 75 nM, respectively.

Synonyms: OSI-906

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of Linsitinib

CAS No. :867160-71-2
Formula : C26H23N5O
M.W : 421.49
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
Synonyms :
OSI-906
English Name :Cis-3-(8-Amino-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutan-1-ol
MDL No. :MFCD12912153
InChI Key :PKCDDUHJAFVJJB-UHFFFAOYSA-N
Pubchem ID :11640390

Safety of Linsitinib

Related Pathways of Linsitinib

RTK

Isoform Comparison

Biological Activity

Target
  • IGF-1R

    IGF-1R, IC50:35 nM

  • Insulin Receptor

    Insulin Receptor, IC50:75 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
CAFs 5 μM Linsitinib evidently inhibited fibroblast proliferation J Clin Invest. 2024 Nov 15;134(22):e183366.
iKras cells 1 μM 24 h Enhanced nab-PTX uptake and cytotoxicity Nat Nanotechnol. 2021 Jul;16(7):830-839.
A549 2 μM 1 day Linsitinib alone or in combination with Dasatinib suppressed the phosphorylation of IGF-1R, Src, and Akt Mol Cancer. 2015 Jun 4;14:113.
H226B 1 μM 5 days Linsitinib treatment increased the stability of IGF-1R and Src proteins, enhancing the reciprocal co-activation of IGF-1R and Src Mol Cancer. 2015 Jun 4;14:113.
liv7k oral cancer cell line 10 µM 72 h To test the drug response of Linsitinib in liv7k oral cancer cells, the results showed cell viability under hypoxic and normoxic conditions. Nat Commun. 2018 Jun 29;9(1):2546.
CAFs 5 μM Linsitinib significantly reduced the CAF-mediated inhibition of T cell migration J Clin Invest. 2024 Nov 15;134(22):e183366.
OMM1.3 cells 1 μM 24 h To study the effect of Linsitinib on UM cell proliferation and cell cycle. It was found that Linsitinib alone had a less significant inhibitory effect on UM cell proliferation. Mol Cancer Ther. 2023 Jan 3;22(1):63-74.
UM001 cells 1 μM 24 h To study the effect of Linsitinib on UM cell proliferation and cell cycle. It was found that Linsitinib alone had a less significant inhibitory effect on UM cell proliferation. Mol Cancer Ther. 2023 Jan 3;22(1):63-74.
92.1 cells 1 μM 24 h To study the effect of Linsitinib on UM cell proliferation and cell cycle. It was found that Linsitinib alone had a less significant inhibitory effect on UM cell proliferation. Mol Cancer Ther. 2023 Jan 3;22(1):63-74.
HCT-15 0.14 μM 96 h Evaluate the effect of Linsitinib on HCT-15 cells, results show that Linsitinib exhibits resistance in HCT-15 cells. Nat Commun. 2024 May 9;15(1):3909.
HT115 0.14 μM 96 h Evaluate the effect of Linsitinib on HT115 cells, results show that Linsitinib exhibits resistance in HT115 cells. Nat Commun. 2024 May 9;15(1):3909.
LS1034 0.14 μM 96 h Evaluate the effect of Linsitinib on LS1034 cells, results show that Linsitinib exhibits sensitivity in LS1034 cells. Nat Commun. 2024 May 9;15(1):3909.
NCI-H508 0.14 μM 96 h Evaluate the effect of Linsitinib on NCI-H508 cells, results show that Linsitinib exhibits sensitivity in NCI-H508 cells. Nat Commun. 2024 May 9;15(1):3909.
SNU-61 0.14 μM 96 h Evaluate the effect of Linsitinib on SNU-61 cells, results show that Linsitinib exhibits resistance in SNU-61 cells. Nat Commun. 2024 May 9;15(1):3909.
HCC4006 1 μM 72 h Evaluate the effect of Linsitinib combined with Osimertinib on HCC4006 cells, results showed that the combination enhanced the effect of Osimertinib. Nat Commun. 2020 Sep 14;11(1):4607.
HCC827 1 μM 72 h Evaluate the effect of Linsitinib combined with Osimertinib on HCC827 cells, results showed that the combination enhanced the effect of Osimertinib. Nat Commun. 2020 Sep 14;11(1):4607.
H3255 1 μM 72 h Evaluate the effect of Linsitinib combined with Osimertinib on H3255 cells, results showed that the combination enhanced the effect of Osimertinib. Nat Commun. 2020 Sep 14;11(1):4607.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice NSCLC xenograft model Oral 25 or 50 mg/kg 6 times per week for 3 weeks Combined treatment with Linsitinib and Dasatinib significantly suppressed tumor growth and increased the levels of active caspase-3 in tumor tissues, while decreasing the expression of PCNA, pIGF-1R, and pSrc Mol Cancer. 2015 Jun 4;14:113.
Mice EO771 and MC38 tumor models Intraperitoneal injection 10 mg/kg Linsitinib significantly enhanced the therapeutic efficacy of immune checkpoint blockade, reduced tumor growth, and prolonged survival J Clin Invest. 2024 Nov 15;134(22):e183366.
NSG mice Metastatic UM mouse model Oral gavage 25-40 mg/kg Daily for two weeks To test the inhibitory effect of Linsitinib in combination with YM-254890 on the growth of metastatic uveal melanoma tumors, results showed that the combination treatment significantly inhibited tumor growth. Mol Cancer Ther. 2023 Jan 3;22(1):63-74.
Mice HCC4006 cell line-derived xenograft model Oral 50 mg/kg Once daily for 10 days Evaluate the effect of Linsitinib combined with Osimertinib on HCC4006 xenograft model, results showed that the combination induced tumor shrinkage and prevented regrowth. Nat Commun. 2020 Sep 14;11(1):4607.
Mice Intracranial xenograft model Oral 50 mg/kg Daily until neurological signs appeared Linsitinib prolonged tumor latency and reduced tumor volumes Cancer Discov. 2021 Feb;11(2):480-499

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02546544 Relapsed Ewing Sarcoma|Refract... More >>ory Ewing Sarcoma Less << PHASE2 COMPLETED 2016-07-15 Universitè Lyon 1 Claude Berna... More >>rd, Lyon, France|Pediatric Hematology and Oncology, University Hospital Münster, Münster, 48149, Germany|Istituti Ortopedici Rizzoli, Bologna, 40136, Italy|Department of Clinical Oncology, Leiden University Medical Center, Leiden, Postzone K1-P, P.O. Box 9600, Netherlands|Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, United Kingdom Less <<
NCT00514007 Advanced Solid Tumors PHASE1 COMPLETED 2012-03-19 Vanderbilt Universtiy Medical ... More >>Center, Nashville, Tennessee, 37232-6307, United States|The Beatson West of Scotland Cancer Centre, Glasgow, G12 0YN, United Kingdom Less <<
NCT00514306 Advanced Solid Tumors PHASE1 COMPLETED 2010-09-20 MD Anderson Cancer Center, Hou... More >>ston, Texas, 77030, United States|Drug Development Unit, Royal Marsden Hospital, Sutton, Surrey, SM2 5PT, United Kingdom Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.37mL

0.47mL

0.24mL

11.86mL

2.37mL

1.19mL

23.73mL

4.75mL

2.37mL

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