Entrectinib

• CAT Number: I000440
• CAS Number: 1108743-60-7
• Molecular Formula: C₃₁H₃₄F₂N₆O₂
• Molecular Weight: 560.64
• Purity: 98%
• Synonyms: (Z)-N-(5-(3,5-difluorobenzyl)-1H-indazol-3(2H)-ylidene)-4-(4-methylpiperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide
• Target: TRK
• Target Protein: P04629,P08922
• Solubility: DMSO: ≥ 33 mg/mL
• Appearance: Solid
• Storage: Dry, dark and at 2 - 8 °C for six months or -20°C for two years.
• IC50: IC50: 1 nM (TrkA), 3 nM (TrkB), 5 nM (TrkC), 12 nM (ROS1), 7 nM (ALK)
• IUPAC Name: N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(oxan-4-ylamino)benzamide
• 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)
• InChIKey: HAYYBYPASCDWEQ-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC(=C(C=C2)C(=O)NC3=NNC4=C3C=C(C=C4)CC5=CC(=CC(=C5)F)F)NC6CCOCC6

Entrectinib（Cat No.:I000440）is an oral, selective tyrosine kinase inhibitor (TKI) that targets ROS1, TRK, and ALK fusion proteins in cancer cells. It is approved for the treatment of ROS1-positive non-small cell lung cancer (NSCLC) and NTRK fusion-positive solid tumors, regardless of the cancer’s origin. By inhibiting these fusion proteins, Entrectinib blocks tumor growth and proliferation. Its ability to cross the blood-brain barrier makes it particularly effective for patients with brain metastases. Entrectinib offers a targeted therapeutic option for patients with advanced, mutation-driven cancers, providing personalized cancer treatment.

Reference

1. Expert Opin Investig Drugs. 2015;24(11):1493-500. doi:
10.1517/13543784.2015.1096344. Epub 2015 Oct 12.

Entrectinib: a potent new TRK, ROS1, and ALK inhibitor.

Rolfo C(1), Ruiz R(2), Giovannetti E(3), Gil-Bazo I(4), Russo A(5), Passiglia
F(1)(5), Giallombardo M(1), Peeters M(1), Raez L(6).

Author information:
(1)a Phase I – Early Clinical Trials Unit, Oncology Department , Antwerp
University Hospital and Center for Oncological Research (CORE), Antwerp
University , Edegem , Belgium.
(2)b Oncology Department , National Cancer Institute (INEN) , Lima , Peru.
(3)c Department Medical Oncology , VU University Medical Center , Amsterdam , The
Netherlands.
(4)d Department of Oncology , Clínica Universidad de Navarra , Pamplona , Spain.
(5)e Department of Surgical, Oncological and Oral Sciences, Section of Medical
Oncology , University of Palermo , Palermo , Italy.
(6)f Thoracic Oncology Program , Memorial Cancer Institute, Memorial Health Care
System , Pembroke Pines , FL , USA.

INTRODUCTION: Receptor tyrosine kinases (RTKs) and their signaling pathways,
control normal cellular processes; however, their deregulation play important
roles in malignant transformation. In advanced non-small cell lung cancer
(NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the
development of molecularly targeted agents that only benefit roughly 20% of
patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent
anti-neoplastic activity and tolerability in various neoplastic conditions,
particularly NSCLC.
AREAS COVERED: This review outlines the pharmacokinetics, pharmacodynamics,
mechanism of action, safety, tolerability, pre-clinical studies and clinical
trials of entrectinib, a promising novel agent for the treatment of advanced
solid tumors with molecular alterations of Trk-A, B and C, ROS1 or ALK.
EXPERT OPINION: Among the several experimental drugs under clinical development,
entrectinib is emerging as an innovative and promising targeted agent. The
encouraging antitumor activity reported in the Phase 1 studies, together with the
acceptable toxicity profile, suggest that entrectinib, thanks to its peculiar
mechanism of action, could play an important role in the treatment-strategies of
multiple TRK-A, B, C, ROS1, and ALK- dependent solid tumors, including NSCLC and
colorectal cancer. That being said, further evidence for its clinical use is
still needed.