1. Protein Tyrosine Kinase/RTK Neuronal Signaling
  2. ROS Kinase Trk Receptor Anaplastic lymphoma kinase (ALK)
  3. Repotrectinib

Repotrectinib (TPX-0005) est un inhibiteur puissant de ROS1 (IC50=0.07 nM) et TRK (IC50=0.83/0.05/0.1 nM pour l'inhibiteur TRKA/B/C). Repotrectinib inhibe puissamment le WT ALK (IC50=1.01 nM). Repotrectinib a une activité anticancéreuse.

Repotrectinib (TPX-0005) is a potent ROS1 (IC50=0.07 nM) and TRK (IC50=0.83/0.05/0.1 nM for TRKA/B/C) inhibitor. Repotrectinib potently inhibits WT ALK (IC50=1.01 nM). Repotrectinib has anti-cancer activity.

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

CAS No. : 1802220-02-5

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Customer Review

Based on 7 publication(s) in Google Scholar

Other Forms of Repotrectinib:

Top Publications Citing Use of Products

    Repotrectinib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Jun 16;16(1):5283.  [Abstract]

    Repotrectinib (1-1000 nM; 72 h) showed specific and significant activity in NTRK-Mono and NTRK-Pleo cell lines in vitro.

    Repotrectinib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Jun 16;16(1):5283.  [Abstract]

    Repotrectinib (2 mg/mL; i.g.; twice daily for 3 weeks) resulted in profound antitumor activity and complete tumor regression in mice bearing an NTRK-Mono allograft model.

    Repotrectinib purchased from MedChemExpress. Usage Cited in: Mol Cancer Ther. 2025 Jul 2;24(7):1005-1019.  [Abstract]

    Repotrectinib (15-75 mg/kg; twice daily for 24 d). Weight changes and survival analysis of Ba/F3 CD74-ROS1 G2032R luciferase mice.

    Repotrectinib purchased from MedChemExpress. Usage Cited in: Mol Cancer Ther. 2025 Jul 2;24(7):1005-1019.  [Abstract]

    Graph showed the number of resistant wells out of 480 and the distribution of kinase domain mutations among sequenced wells for Repotrectinib (5.6-28 nM; 28 d) in Ba/F3 CD74-ROS1 cells.

    Repotrectinib purchased from MedChemExpress. Usage Cited in: Cancer Discov. 2023 Mar 1;13(3):598-615.  [Abstract]

    Repotrectinib (15-75 mg/kg; i.g.; twice daily for 14 d) induced regression in the Ba/F3 CD74-ROS1 G2032R xenograft mice.

    View All Trk Receptor Isoform Specific Products:

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Repotrectinib (TPX-0005) is a potent ROS1 (IC50=0.07 nM) and TRK (IC50=0.83/0.05/0.1 nM for TRKA/B/C) inhibitor. Repotrectinib potently inhibits WT ALK (IC50=1.01 nM). Repotrectinib has anti-cancer activity[1][2].

    IC50 & Target

    TrkA

     

    Cellular Effect
    Cell Line Type Value Description References
    BaF3 IC50
    0.66 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring wild type ETV6-TRKB incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring wild type ETV6-TRKB incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    0.7 nM
    Compound: TPX-0005
    Cytotoxicity against mouse BaF3 cells transfected with TrKA F589L mutant assessed as reduction in cell viability by MTT assay
    Cytotoxicity against mouse BaF3 cells transfected with TrKA F589L mutant assessed as reduction in cell viability by MTT assay
    [PMID: 34253025]
    BaF3 IC50
    0.88 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G667A mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G667A mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    0.98 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC F617L mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC F617L mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    1.14 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G696A mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G696A mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    1.39 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRK1 fusion protein incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRK1 fusion protein incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    1.61 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring TRKA-F589L fusion protein incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring TRKA-F589L fusion protein incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    1.8 nM
    Compound: TPX-0005
    Cytotoxicity against mouse BaF3 cells transfected with TrKA assessed as reduction in cell viability by MTT assay
    Cytotoxicity against mouse BaF3 cells transfected with TrKA assessed as reduction in cell viability by MTT assay
    [PMID: 34253025]
    BaF3 IC50
    1.9 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-NTRK3 fusion protein incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-NTRK3 fusion protein incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    10.67 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRK1 G595R mutant fusion protein incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRK1 G595R mutant fusion protein incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    10.83 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB V617M mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB V617M mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    12.28 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA V573M mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA V573M mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    15.66 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRK1 G667C mutant fusion protein incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRK1 G667C mutant fusion protein incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    158.95 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G595R/G667C mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G595R/G667C mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    17.04 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G696C mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G696C mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    19.3 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB G639R mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB G639R mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    2.15 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB F633L mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB F633L mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    2.2 nM
    Compound: TPX-0005
    Cytotoxicity against mouse BaF3 cells transfected with SLC34A2-Ros1 assessed as reduction in cell viability by MTT assay
    Cytotoxicity against mouse BaF3 cells transfected with SLC34A2-Ros1 assessed as reduction in cell viability by MTT assay
    [PMID: 34253025]
    BaF3 IC50
    208 nM
    Compound: TPX-0005
    Antiproliferative activity against EML4-ALK-L1196M/G1202R mutated mouse BaF3 cells assessed as cell growth inhibition by CCK-8 assay
    Antiproliferative activity against EML4-ALK-L1196M/G1202R mutated mouse BaF3 cells assessed as cell growth inhibition by CCK-8 assay
    [PMID: 37127101]
    BaF3 IC50
    23.07 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC V601M mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC V601M mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    3.32 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRKIF 589L mutant fusion protein incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-NTRKIF 589L mutant fusion protein incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    4.59 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G6968 mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G6968 mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    4.8 nM
    Compound: TPX-0005
    Cytotoxicity against mouse BaF3 cells transfected with TrKA G623R mutant assessed as reduction in cell viability by MTT assay
    Cytotoxicity against mouse BaF3 cells transfected with TrKA G623R mutant assessed as reduction in cell viability by MTT assay
    [PMID: 34253025]
    BaF3 IC50
    5.4 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G623E mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G623E mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    5.75 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G623R mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKC G623R mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    78.32 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G595R/G667A mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G595R/G667A mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    8 nM
    Compound: TPX-0005
    Cytotoxicity against mouse BaF3 cells transfected with TrKA G595R mutant assessed as reduction in cell viability by MTT assay
    Cytotoxicity against mouse BaF3 cells transfected with TrKA G595R mutant assessed as reduction in cell viability by MTT assay
    [PMID: 34253025]
    BaF3 IC50
    8.12 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G6678 mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring CD74-TRKA G6678 mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    892.25 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    9.44 nM
    Compound: 4
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB G709C mutant incubated for 3 days by CCK8 method
    Antiproliferative activity against mouse BaF3 cells harbouring ETV6-TRKB G709C mutant incubated for 3 days by CCK8 method
    [PMID: 37676745]
    BaF3 IC50
    < 0.2 nM
    Compound: Repotrectinib
    Antiproliferative activity against mouse BaF3 cells harboring TRKA F589L mutant assessed as cell growth inhibition
    Antiproliferative activity against mouse BaF3 cells harboring TRKA F589L mutant assessed as cell growth inhibition
    [PMID: 36395392]
    KARPAS-299 IC50
    40 nM
    Compound: TPX-0005
    Antiproliferative activity against human KARPAS-299 cells assessed as cell growth inhibition by CCK-8 assay
    Antiproliferative activity against human KARPAS-299 cells assessed as cell growth inhibition by CCK-8 assay
    [PMID: 37127101]
    NCI-H1373 IC50
    5000 nM
    Compound: 1
    Cytotoxicity against human NCI-H1373 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    Cytotoxicity against human NCI-H1373 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    [PMID: 34676026]
    NCI-H1792 IC50
    1901 nM
    Compound: 1
    Cytotoxicity against human NCI-H1792 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    Cytotoxicity against human NCI-H1792 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    [PMID: 34676026]
    NCI-H2122 IC50
    1936 nM
    Compound: 1
    Cytotoxicity against human NCI-H2122 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    Cytotoxicity against human NCI-H2122 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    [PMID: 34676026]
    NCI-H23 IC50
    4059 nM
    Compound: 1
    Cytotoxicity against human NCI-H23 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    Cytotoxicity against human NCI-H23 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    [PMID: 34676026]
    NCI-H358 IC50
    2500 nM
    Compound: 1
    Cytotoxicity against human NCI-H358 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    Cytotoxicity against human NCI-H358 cells harboring KRAS G12C mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luciferase-based ATP detection assay
    [PMID: 34676026]
    In Vitro

    Repotrectinib (TPX-0005) inhibits mutant ALKs including ALK G1202R (IC50=1.26 nM) and ALK L1196M (IC50=1.08 nM). Repotrectinib also inhibits a variety of other kinases, including JAK2, LYN, Src, and FAK (IC50=1.04, 1.66, 5.3, and 6.96 nM, respectively)[1].
    Repotrectinib effectively overcomes this primary resistance (IC50=100 nM in cell proliferation assay) with strong inhibition of the phosphorylation of EML4-ALK (IC50=13 nM) and the SRC substrate paxillin (IC50=107 nM). Repotrectinib inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib[1].

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

    In Vivo

    Repotrectinib (TPX-0005) effectively inhibits tumor growth in vivo in ALK WT and ALK G1202R xenografts[1].

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

    Clinical Trial
    Molecular Weight

    355.37

    Formula

    C18H18FN5O2

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    O=C1NC[C@H](C)OC2=CC=C(F)C=C2[C@@H](C)NC3=NC4=C1C=NN4C=C3

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 25 mg/mL (70.35 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.8140 mL 14.0698 mL 28.1397 mL
    5 mM 0.5628 mL 2.8140 mL 5.6279 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (7.03 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 2.5 mg/mL (7.03 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    In Vivo Dissolution Calculator
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.95%

    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.8140 mL 14.0698 mL 28.1397 mL 70.3492 mL
    5 mM 0.5628 mL 2.8140 mL 5.6279 mL 14.0698 mL
    10 mM 0.2814 mL 1.4070 mL 2.8140 mL 7.0349 mL
    15 mM 0.1876 mL 0.9380 mL 1.8760 mL 4.6899 mL
    20 mM 0.1407 mL 0.7035 mL 1.4070 mL 3.5175 mL
    25 mM 0.1126 mL 0.5628 mL 1.1256 mL 2.8140 mL
    30 mM 0.0938 mL 0.4690 mL 0.9380 mL 2.3450 mL
    40 mM 0.0703 mL 0.3517 mL 0.7035 mL 1.7587 mL
    50 mM 0.0563 mL 0.2814 mL 0.5628 mL 1.4070 mL
    60 mM 0.0469 mL 0.2345 mL 0.4690 mL 1.1725 mL
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