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Purity: =99.03%
Entrectinib (formerly also known as NMS-E628; RXDX-101; trade name ROZLYTREK) is a potent and orally bioavailable small molecule inhibitor of TrkA, TrkB, TrkC, ROS1 and ALK with potential antitumor activity. With respective IC50 values of 1, 3, 5, 12, and 7 nM, it inhibits the kinases listed above. The US FDA approved entrectinib in 2019 for the treatment of NTRK fusion-positive solid tumors and ROS1-positive non-small cell lung cancer (NSCLC). In May 2020, Australia approved it for NSCLC, and in July 2020, the European Union approved it as well.
| Targets |
TrkA (IC50 = 1 nM); TrkB (IC50 = 3 nM); TrkC (IC50 = 5 nM); ROS1 (IC50 = 12 nM); ALK (IC50 = 7 nM)
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| ln Vitro |
Entrectinib potently inhibits ALK-dependent signaling and specifically prevents the proliferation of ALK-dependent cell lines. Entrectinib also significantly suppresses the NSCLC cell line NCI-H2228, which has an EML4-ALK rearrangement, in terms of cell growth. [2]
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| ln Vivo |
Entrectinib (p.o.) causes total tumor regression in mice with xenografts of Karpas-299 and SR-786. Entrectinib causes the tumor masses seen in the lymph nodes and thymus of NPM-ALK transgenic mice to completely disappear.[2]
Entrectinib cotreatment increased the effectiveness of traditional chemotherapy in the NB xenograft model.[3] |
| Enzyme Assay |
Entrectinib inhibits TrkA, TrkB, TrkC, ROS1, and ALK with IC50 values of 1, 3, 5, 12, and 7 nM, respectively. It is a strong and readily available oral inhibitor of Trk, ROS1, and ALK.
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| Cell Assay |
Plated in 96-well plates, NLF, NLF-TrkB, SY5Y, or SY5Y-TrkB cells are subjected to varying concentrations of entrectinib (1, 5, 10, 20, 30, 50, and 100 nM, 1.5 μM Irino, and 50 μM TMZ, respectively) for a duration of one hour. Subsequently, 100 ng/mL of BDNF is added. After the drug is added, plates are harvested 24, 48, and 72 hours later. The plates are prepared, and an SRB assay protocol is used to analyze the cell viability.
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| Animal Protocol |
Male C57BL/6 mice (6-8 weeks old, 20-25 g; Bleomycin-induced pulmonary fibrosis model)[1].
20, 40, 60 mg/kg Intragastric Administration; single daily for 7 days. |
| References |
| Molecular Formula |
C31H34F2N6O2
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| Molecular Weight |
560.64
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| Exact Mass |
560.27
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| Elemental Analysis |
C, 66.41; H, 6.11; F, 6.78; N, 14.99; O, 5.71
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| CAS # |
1108743-60-7
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6
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| InChi Key |
HAYYBYPASCDWEQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H34F2N6O2/c1-38-8-10-39(11-9-38)25-3-4-26(29(19-25)34-24-6-12-41-13-7-24)31(40)35-30-27-17-20(2-5-28(27)36-37-30)14-21-15-22(32)18-23(33)16-21/h2-5,15-19,24,34H,6-14H2,1H3,(H2,35,36,37,40)
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| Chemical Name |
N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide
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| Synonyms |
Entrectinib, RXDX-101, NMS-E628; RXDX101; RXDX 101; RXDX-101; NMS E628; NMS-E-628; trade name: ROZLYTREK
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.46 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.08 mg/mL (3.71 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 5: ≥ 2.08 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 6: 5 mg/mL (8.92 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04589832 | Active Recruiting |
Drug: PAC-1 Drug: Entrectinib |
Uveal Melanoma | Arkadiusz Z. Dudek, MD | January 11, 2021 | Phase 1 Phase 2 |
| NCT02568267 | Active Recruiting |
Drug: Entrectinib | Breast Cancer Melanoma |
Hoffmann-La Roche | November 19, 2015 | Phase 2 |
| NCT02650401 | Active Recruiting |
Drug: Entrectinib | Solid Tumors CNS Tumors |
Hoffmann-La Roche | May 3, 2016 | Phase 1 Phase 2 |
| NCT05770544 | Recruiting | Drug: Entrectinib | Solid Tumor Cancer |
Cancer Research UK | December 2023 | Phase 2 Phase 3 |
| NCT03994796 | Recruiting | Drug: Entrectinib Drug: Adagrasib |
CDK Gene Mutation PI3K Gene Mutation |
Alliance for Clinical Trials in Oncology |
August 15, 2019 | Phase 2 |
Mechanism of action and in vivo activity of entrectinib in ALK-driven ALCL cell lines and xenograft models.Mol Cancer Ther.2016 Apr;15(4):628-39. |
In vivo activity of entrectinib in an NPM-ALK transgenic model.Mol Cancer Ther.2016 Apr;15(4):628-39. |
Activity of entrectinib against NCI-H2228 NSCLC tumors.Mol Cancer Ther.2016 Apr;15(4):628-39. |
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