Chemical Probes logo
Linsitinib | Inhibitor of IGF1R, INSR, INSRR
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
IGF1R
  • IC50:35 nM
  • IC50:24 nM
INSR
  • IC50:75 nM
  • IC50:39 nM
INSRR
  • IC50:75 nM
    Inhibitor
    100 - 1000 nM

    Selectivity

    In Vitro Selectivity Assessment
    Potency Assay Off-Target:
    Linsitinib was tested against 88 kinases (Kinase Profiler, Upstate Inc) and 42 receptor tyrosine kin ...
    Selectivity Assessment Description:
    Negligible inhibition of CYP3A4, CYP2D6 and CYP1A2 (IC50 >10 uM)

    Potency
    Cellular
    In Vitro

    IGF1R

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.4155/fmc.09.89

    INSR

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.4155/fmc.09.89

    INSRR

    Mode of Action: Inhibitor

    Structure-Activity-Relationship data available? No

    DOI Reference: 10.4155/fmc.09.89

    In Vivo Validations

    Mouse, Rat
    Dose: 5 mg/kg, 50-75 mg/Kg Oral (Reviewer Suggested)
    Route of delivery: Intravenous, Oral
    Plasma half life: 2.14 h (mouse, IV), 2.64 h (rat, IV)
    Systemic clearance: 12 mL/min/kg (mouse, IV), 4 mL/min/kg (rat, IV)
    Organ of interest (O): LISN xenograft
    Target engagement assay: In xenografts, linsitinib dose-dependently inhibited IGF1R autophosphorylation (IC50=1.28 uM).

    DOI Reference: 10.4155/fmc.09.89

    Chemical Information

    Molecular Formula C26H23N5O
    SMILEs C[C@]1(O)C[C@@H](c2nc(-c3ccc4ccc(-c5ccccc5)nc4c3)c3c(N)nccn32)C1
    InChI 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+
    Molecular weight 421.19 Da
    AlogP 0.0
    HBond acceptors 6
    HBond donors 3
    Atoms 55

    References

    Publications

    Cross References

    canSARChEMBLBindingDBGDSC1GDSC2

    Vendors

    Note: This is not an exhaustive list and does not indicate endorsement by the portal.

    Expert Reviews

    by SERP
    (on 28 Jul 2017 )
    Cellular Use Rating
    In Model Organisms
    This is the best available probe for INSRR and IRR. A panel of 88 kinases was profiled when selectivity was assessed.
    by SERP
    (on 10 Nov 2020 )
    Cellular Use Rating
    In Model Organisms
    Linsitinib (OSI-906) has excellent kinase selectivity, and is quite potent against the indicated kinases that it does inhibit. It shows very good in vivo activity, and is orally bioavailable. Together,...
    by SERP
    (on 16 Nov 2020 )
    Cellular Use Rating
    In Model Organisms
    This is a dual selective IGF1R & INSR (and related INSRR) kinase inhibitor with demonstrated kinase selectivity an cell-based assay activity with oral bioavailability.
    Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria