Home Protein Tyrosine Kinase Trk receptor inhibitor - ALK inhibitor - ROS1 inhibitor - Autophagy activator Entrectinib For research use only.

Entrectinib

Synonyms: RXDX-101, NMS-E628

Entrectinib is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2.

Entrectinib Chemical Structure

Entrectinib Chemical Structure

CAS No. 1108743-60-7

Purity & Quality Control

Entrectinib Related Products

Signaling Pathway

Trk receptor Signaling Pathways

Trk receptor Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAF3 Function assay 72 hrs Inhibition of human TEL (336 residues) fused-TRKB (455 to 822 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM. 27003761
BAF3 Function assay 72 hrs Inhibition of human TEL (336 residues) fused-TRKA (440 to 796 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM. 27003761
BAF3 Function assay 72 hrs Inhibition of human TEL (336 residues) fused-TRKC (454 to 825 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.003 μM. 27003761
BAF3 Function assay 72 hrs Inhibition of human TEL (336 residues) fused-ROS1 (1891 to 2347 residues) (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.005 μM. 27003761
KM12 Antiproliferative assay 72 hrs Antiproliferative activity against human KM12 cells expressing TRKA protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.017 μM. 27003761
SU-DHL1 Antiproliferative assay 72 hrs Antiproliferative activity against human SU-DHL1 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.024 μM. 27003761
BAF3 Function assay 72 hrs Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.028 μM. 27003761
KARPAS299 Antiproliferative assay 72 hrs Antiproliferative activity against human KARPAS299 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 0.031 μM. 27003761
SUP-M2 Antiproliferative assay 72 hrs Antiproliferative activity against human SUP-M2 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.041 μM. 27003761
BAF3 Function assay 72 hrs Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.067 μM. 27003761
NCI-H2228 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H2228 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.068 μM. 27003761
MV411 Antiproliferative assay 72 hrs Antiproliferative activity against human MV411 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 0.081 μM. 27003761
SR786 Antiproliferative assay 72 hrs Antiproliferative activity against human SR786 cells expressing ALK protein incubated for 72 hrs by cell titer-glo assay, IC50 = 0.081 μM. 27003761
BAF3 Function assay 72 hrs Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by cell titer-glo assay, IC50 = 0.897 μM. 27003761
BA/F3 Cytotoxicity assay 72 hrs Cytotoxicity against mouse IL-3 dependent BA/F3 cells incubated for 72 hrs by cell titer-glo assay, IC50 = 2.104 μM. 27003761
KM12 Function assay 2 hrs Inhibition of TPM3-TRKA phosphorylation in human KM12 cells at low concentration after 2 hrs by Western blot analysis 27003761
KM12 Function assay 2 hrs Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of MAPK phosphorylation at low concentration after 2 hrs by Western blot analysis 27003761
KM12 Function assay 2 hrs Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of PLCgamma1 phosphorylation at low concentration after 2 hrs by Western blot analysis 27003761
KM12 Function assay 2 hrs Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of AKT phosphorylation at low concentration after 2 hrs by Western blot analysis 27003761
KM12 Function assay 2 hrs Inhibition of TPM3-TRKA phosphorylation in human KM12 cells assessed as suppression of S6 phosphorylation at low concentration after 2 hrs by Western blot analysis 27003761
KARPAS299 Function assay 60 mg/kg 12 hrs Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis 27003761
KARPAS299 Function assay 60 mg/kg 18 hrs Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis 27003761
KARPAS299 Function assay 60 mg/kg 12 hrs Ex vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells assessed as suppression of STAT3 phosphorylation at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis 27003761
KARPAS299 Function assay 60 mg/kg 18 hrs In vivo inhibition of NPM-ALK phosphorylation in SCID mouse xenografted with human KARPAS299 cells assessed as suppression of STAT3 phosphorylation at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis 27003761
NCI-H2228 Antitumor assay 30 to 60 mg/kg 10 days Antitumor activity against human NCI-H2228 cells xenografted in athymic nu/nu mouse assessed as tumor growth inhibition at 30 to 60 mg/kg, po bid administered for 10 days 27003761
NCI-H2228 Function assay 60 mg/kg 12 hrs Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis 27003761
NCI-H2228 Function assay 60 mg/kg 18 hrs Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis 27003761
NCI-H2228 Function assay 60 mg/kg 12 hrs Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells assessed as suppression of AKT phosphorylation at 60 mg/kg, po administered as single dose measured after 12 hrs by Western blot analysis 27003761
NCI-H2228 Function assay 60 mg/kg 18 hrs Ex vivo inhibition of EML4-ALK phosphorylation in athymic nu/nu mouse xenografted with human NCI-H2228 cells assessed as suppression of AKT phosphorylation at 60 mg/kg, po administered as single dose measured after 18 hrs by Western blot analysis 27003761
KARPAS299 Antitumor assay 30 to 60 mg/kg 10 days Antitumor activity against human KARPAS299 cells xenografted in SCID mouse assessed as tumor growth inhibition at 30 to 60 mg/kg, po bid administered for 10 days 27003761
KARPAS299 Antitumor assay 30 to 60 mg/kg 10 days Antitumor activity against human KARPAS299 cells xenografted in SCID mouse assessed as tumor free cured mouse at 30 to 60 mg/kg, po bid administered for 10 days measured on day 90 27003761
KARPAS299 Function assay 2 hrs Inhibition of NPM/ALK autophosphorylation in human KARPAS299 cells at very low concentration after 2 hrs by Western blot analysis 27003761
NCI-H2228 Function assay 2 hrs Inhibition of NPM/ALK autophosphorylation in human NCI-H2228 cells at very low concentration after 2 hrs by Western blot analysis 27003761
Click to View More Cell Line Experimental Data

Biological Activity

Description Entrectinib is an orally bioavailable pan-TrkA/B/C, ROS1 and ALK inhibitor with IC50 ranging between 0.1 and 1.7 nM. Entrectinib (RXDX-101) induces autophagy. Phase 2.
Targets
TrkA [1] TrkB [1] TrkC [1] ROS1 [1] ALK [1]
In vitro
In vitro

Entrectinib selectively blocks proliferation of ALK-dependent cell lines and potently inhibits ALK‐dependent signaling. Entrectinib also highly inhibits cell growth of the NSCLC cell line NCI‐H2228 bearing the EML4-ALK rearrangement. [2]
Experimental Result Images Methods Biomarkers Images PMID
Western blot pAKT / AKT pTrkA-Y490 / TrkA / p-PLCγ-Y783 / PLCγ p-ALK / ALK / p-ERK / ERK / p-STAT3 / STAT3 Cyclin A1 / Cyclin E1 / p27 / p21 26172300
Growth inhibition assay Cell viability 26172300
In Vivo
In vivo

In mice bearing Karpas-299 and SR-786 xenografts, Entrectinib (p.o.) induces complete tumor regression. In NPM-ALK transgenic mice, Entrectinib induces complete regression of tumor masses observed in the thymus and in lymph nodes. [2]

In the NB xenograft model, Entrectinib cotreatment enhanced the efficacy of conventional chemotherapy. [3]
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05770544 Recruiting
Solid Tumor|Haematological Malignancy|Malignancy|Malignant Neoplasm|Lymphoproliferative Disorders|Neoplasms by Histologic Type|Neoplasms by Site|Cancer|Brain Neoplasms|Melanoma|Glioma
Cancer Research UK|University of Manchester|University of Birmingham|Royal Marsden NHS Foundation Trust|Hoffmann-La Roche
 June 2024 Phase 2|Phase 3
NCT04551495 Recruiting
Invasive Lobular Breast Carcinoma|ER+ Breast Cancer|HER2-negative Breast Cancer
Jules Bordet Institute|Hoffmann-La Roche
 January 14 2021 Phase 2
NCT04226833 Completed
Hepatic Insufficiency
Hoffmann-La Roche
 February 11 2020 Phase 1
NCT03796013 Completed
Healthy Volunteers
Genentech Inc.
 January 10 2019 Phase 1

Chemical Information & Solubility

Molecular Weight 560.64 Formula

C31H34F2N6O2
CAS No. 1108743-60-7 SDF Download Entrectinib SDF
Smiles CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (178.36 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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Tech Support

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