1. JAK/STAT Signaling
    Protein Tyrosine Kinase/RTK
  2. EGFR
    VEGFR
    Ephrin Receptor

XL-647 (Synonyms: Tesevatinib; EXEL-7647; KD-019)

Cat. No.: HY-13314 Purity: 99.21%
Handling Instructions

XL-647 (Tesevatinib;XL-647;KD-019) is an orally available, multi-target tyrosine kinase inhibitor; inhibits EGFR, ErbB2, KDR, Flt4 and EphB4 kinase with IC50s of 0.3, 16, 1.5, 8.7, and 1.4 nM.

For research use only. We do not sell to patients.

XL-647 Chemical Structure

XL-647 Chemical Structure

CAS No. : 781613-23-8

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 396 In-stock
Estimated Time of Arrival: December 31
5 mg USD 360 In-stock
Estimated Time of Arrival: December 31
10 mg USD 648 In-stock
Estimated Time of Arrival: December 31
50 mg   Get quote  
100 mg   Get quote  

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    XL-647 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    XL-647 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    XL-647 (Tesevatinib;XL-647;KD-019) is an orally available, multi-target tyrosine kinase inhibitor; inhibits EGFR, ErbB2, KDR, Flt4 and EphB4 kinase with IC50s of 0.3, 16, 1.5, 8.7, and 1.4 nM.

    IC50 & Target[1]

    EGFR

    0.3 nM (IC50)

    ErbB2

    16 nM (IC50)

    KDR

    1.5 nM (IC50)

    Flt-4

    8.7 nM (IC50)

    In Vitro

    XL-647 potently inhibits the EGF/ErbB2, VEGF, and ephrin RTK families. XL-647 is a reversible and ATP competitive inhibitor. XL-647 was inactive against a panel of 10 tyrosine kinases (including the insulin and the insulin-like growth factor-1 receptor) and 55 serine-threonine kinases (including cyclin-dependent kinases, stress-activated protein kinases, and protein kinase C isoforms). XL-647 inhibits cellular proliferation and EGFR pathway activation in the erlotinib-resistant H1975 cell line that harbors a double mutation (L858R and T790M) in the EGFR gene. In A431 cells, XL-647 reduces cell viability with IC50 values of 13 nM[1].

    In Vivo

    XL-647 shows potent and long-lived inhibition of the WT EGFR in vivo. XL-647 substantially inhibits the growth of H1975 xenograft tumors and reduces both tumor EGFR signaling and tumor vessel density[1].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 30 mg/mL (61.05 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.0350 mL 10.1752 mL 20.3504 mL
    5 mM 0.4070 mL 2.0350 mL 4.0701 mL
    10 mM 0.2035 mL 1.0175 mL 2.0350 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Kinase Assay
    [1]

    A431 cells are seeded at 50000 per well in 96-well microtiter plates and incubated in fully supplemented DMEM for 16 h after which growth medium is replaced with serum-free DMEM and the cells are incubated for an additional 24 h. Serial dilutions of XL-647 (in triplicate) in serum-free medium are added to the quiescent cells and incubated for 1 h before stimulation with 100 ng/mL recombinant human EGF for 10 min. Negative control wells do not receive EGF. After treatment, cell monolayers are washed with cold PBS and immediately lysed with cold lysis buffer. Lysates are centrifuged, transferred to 96-well streptavidin-coated plates containing biotin-conjugated, mouse monoclonal anti-human EGFR (2 μg/mL), and incubated for 2 h. Plates are washed thrice with TBST and incubated with horseradish peroxidase–conjugated anti-phosphotyrosine antibody. Horseradish peroxidase activity is determined by reading the plates[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    Growth inhibition of H1975 and A431 cells by increasing concentrations of XL-647, gefitinib, or erlotinib is determined by seeding 5000 cells per well in 96-well plates. The following day, cells are washed once with low-serum RPMI 1640 (0.1% fetal bovine serum, 1% nonessential amino acids, and 1% penicillin/streptomycin), after which 90 μL of the low-serum RPMI 1640 are added. Test compounds (XL-647) are diluted to 10 times the test concentrations and 10 μL are added to triplicate wells for a 72-h incubation. Cell viability is determined[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice: Tumor-bearing mice are given either XL-647, erlotinib, or gefitinib at 100 mg/kg and tumors are harvested 1 to 72 h later. Half an hour before respective time point, EGF (50 μg/mouse) is given via i.v. bolus injection with tumors dissected 30 min later and tumor extracts are prepared by homogenization in 10 volumes of ice-cold lysis buffer. Lysates are clarified by centrifugation and EGFR tyrosine phosphorylation levels are determined by ELISA[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    491.39

    Formula

    C₂₄H₂₅Cl₂FN₄O₂

    CAS No.

    781613-23-8

    SMILES

    [H][[email protected]@]12[[email protected]@](C[[email protected]@H](COC3=CC4=C(C(NC5=C(F)C(Cl)=C(Cl)C=C5)=NC=N4)C=C3OC)C2)([H])CN(C)C1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.21%

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    XL-647
    Cat. No.:
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    Cat. No.: HY-13314