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

Size Price Stock Quantity
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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  • 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
NCT Number Sponsor Condition Start Date Phase
NCT02568267 Ignyta, Inc. Breast Cancer|Cholangiocarcinoma|Colorectal Cancer|Head and Neck Neoplasms|Lymphoma, Large-Cell, Anaplastic|Melanoma|Neuroendocrine Tumors|Non-Small Cell Lung Cancer|Ovarian Cancer|Pancreatic Cancer|Papillary Thyroid Cancer|Primary Brain Tumors|Renal Cell Carcinoma|Sarcomas|Salivary Gland Cancers|Adult Solid Tumor October 2015 Phase 2
NCT03066661 Ignyta, Inc. Cancers With NTRK, ROS1, or ALK Gene Fusions
NCT02097810 Ignyta, Inc. Locally Advanced Solid Tumors|Metastatic Solid Tumors June 2014 Phase 1
NCT02650401 Ignyta, Inc. Solid Tumors|CNS Tumors|Neuroblastoma December 2015 Phase 1
NCT02587650 Adil Daud|University of California, San Francisco Melanoma May 2016 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
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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Entrectinib
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