1. Protein Tyrosine Kinase/RTK
    Autophagy
  2. ALK
    ROS
    Trk Receptor
    Autophagy

Entrectinib (Synonyms: NMS-E628; RXDX-101)

Cat. No.: HY-12678 Purity: 98.42%
Data Sheet SDS Handling Instructions

Entrectinib is a potent and orally available Trk, ROS1, and ALK inhibitor; inhibits TrkA, TrkB, TrkC, ROS1 and ALK with IC50 values of 1, 3, 5, 12 and 7 nM, respectively.

For research use only. We do not sell to patients.
Entrectinib Chemical Structure

Entrectinib Chemical Structure

CAS No. : 1108743-60-7

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $93 In-stock
5 mg $75 In-stock
10 mg $120 In-stock
50 mg $450 In-stock
100 mg $740 In-stock
200 mg   Get quote  
500 mg   Get quote  

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

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    Entrectinib 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.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Entrectinib is a potent and orally available Trk, ROS1, and ALK inhibitor; inhibits TrkA, TrkB, TrkC, ROS1 and ALK with IC50 values of 1, 3, 5, 12 and 7 nM, respectively.

    IC50 & Target

    IC50: 1 nM (TrkA), 1 nM (TrkB), 1 nM (TrkC), 1 nM (ROS1),1 nM (ALK)[1]

    In Vitro

    Entrectinib is found to be exquisitely active in inhibiting the proliferation of a limited number of cell lines: the TRKA-driven colorectal carcinoma cell line KM12 (IC50 of 17 nM), the ALK-dependent ALCL cell lines SU-DHL-1, Karpas-299, SUP-M2 and SR-786 (IC50 of 20, 31, 41, and 81 nM, respectively), the ALK-dependent NSCLC cell line NCI-H2228 (IC50 of 68 nM) and the FLT3-dependent AML cell line MV-4-11 (IC50 of 81 nM). Entrectinib potently blocks proliferation of Ba/F3-TEL-TRKB (IC50 of 2.9 nM), Ba/F3-TEL-TRKC (IC50 of 3.3 nM), and Ba/F3-TEL-ROS1 (IC50 of 5.3 nM) cells, with a high degree of selectivity versus parental Ba/F3 cells or those transformed by nontargeted kinases such as ABL and RET, which are inhibited with IC50s in the range of 2 to 3 μM[1]. Entrectinib significantly inhibits the growth of TrkB-expressing NB cells in vitro, and it significantly enhances the growth inhibition of Irino-TMZ when used in combination[2].

    In Vivo

    Oral administration of entrectinib to tumor-bearing mice induces regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis[1]. Single agent therapy results in significant tumor growth inhibition in animals treated with entrectinib compared to control animals[2].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.7837 mL 8.9184 mL 17.8368 mL
    5 mM 0.3567 mL 1.7837 mL 3.5674 mL
    10 mM 0.1784 mL 0.8918 mL 1.7837 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [2]

    NLF, NLF-TrkB, SY5Y or SY5Y-TrkB cells are plated in 96 well plates, and they are exposed to drug at different concentrations (1, 5, 10, 20, 30, 50 and 100 nM of entrectinib, 1.5 μM Irino and 50 μM TMZ, respectively) for one hr followed by addition of 100 ng/mL of BDNF. Plates are harvested at 24, 48, and 72 hr following addition of drug. The plates are processed and cell viability is analyzed using a standard SRB assay protocol[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    Mouse: Entrectinib is reconstituted in 0.5% methylcellulose containing 1% Tween 80 at a final dosing volume of 10 mL/kg (e.g., 0.2 mL for a 20 gm mouse). Treatment with entrectinib, Irino and TMZ started about 15–17 days after tumor inoculation when the average tumor size is 0.2 cm3. Mice are sacrificed when tumor volume reached 3 cm3. Tumors are harvested and flash frozen on dry ice for analysis of protein expression[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    560.64

    Formula

    C₃₁H₃₄F₂N₆O₂

    CAS No.

    1108743-60-7

    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

    Solvent & Solubility

    DMSO: ≥ 31 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    Inquiry Information

    Product Name:
    Entrectinib
    Cat. No.:
    HY-12678
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