Entrectinib, CAS No. 1108743-60-7, also known as RXDX-101 and NMS-E628, is an oral small molecule inhibitor of TrkA, TrkB and TrkC, as well as ROS1 and ALK, with high potency and selectivity. RXDX-101 has demonstrated potent pharmacological activity in preclinical studies and has the potential to be first-in-class against the Trk family of kinases. PXDX-101 has been well tolerated in patients with advanced solid tumors. PXDX-101 is currently in clinical trials, and is being developed by Ignyta.

Product information

CAS Number: 1108743-60-7

Molecular Weight: 560.64

Formula: C31H34F2N6O2

Synonym:

RXDX101

RXDX 101

NMS E628

NMSE628

RXDX-101

NMS-E628

Chemical Name: N-(5-(3,5-difluorobenzyl)-1H-indazol-3-yl)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide

Smiles: CN1CCN(CC1)C1=CC(NC2CCOCC2)=C(C=C1)C(=O)NC1=NNC2=CC=C(CC3C=C(F)C=C(F)C=3)C=C21

InChiKey: HAYYBYPASCDWEQ-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Entrectinib (NMS-E628) 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. 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

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. Single agent therapy results in significant tumor growth inhibition in animals treated with entrectinib compared to control animals.

References:

1. Entrectinib OK'd for Cancers with NTRK Fusions, NSCLC. Cancer Discov. 2019 Oct;9(10):OF2. doi: 10.1158/2159-8290.CD-NB2019-101. Epub 2019 Aug 30. PubMed PMID: 31471291.
2. Facchinetti F, Friboulet L. Profile of entrectinib and its potential in the treatment of ROS1-positive NSCLC: evidence to date. Lung Cancer (Auckl). 2019 Sep 9;10:87-94. doi: 10.2147/LCTT.S190786. eCollection 2019. PubMed PMID: 31572036; PubMed Central PMCID: PMC6747675.

Products are for research use only. Not for human use.