Entrectinib

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Entrectinib Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Entrectinib (RXDX-101, Ignyta Pharmaceuticals, San Diego, CA, USA) is a small molecule that inhibits the tyrosine kinases TRKA/B/C, ROS1, and ALK (Table?1). It has a preclinical median inhibitory concentration (IC50) of 7?nm against ROS1, higher than crizotinib [95, 96]. Entrectinib was specifically designed to cross the blood-brain barrier [95].

• Beschreibung

  Entrectinib is an inhibitor of TrkA (IC₅₀ = 1.7 nM), TrkB (IC₅₀ = 0.1 nM), and TrkC (IC₅₀ = 0.1 nM), as well as C-ros oncogene 1 (ROS1; IC₅₀ = 0.2 nM) and anaplastic lymphoma kinase (ALK; IC₅₀ = 1.6 nM). Entrectinib blocks proliferation of ALK-dependent cell lines, including those with L1196M or C1156Y resistance mutations, and inhibits ALK‐dependent signaling. It has been shown to inhibit the growth of a non-small cell lung cancer cell line bearing an EML4-ALK rearrangement. In mice bearing various Trk, ROS1, or ALK-driven xenografts, entrectinib has been shown to induce tumor regression.

• Verwenden

  Entrectinib, 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.

• Trademarks

  Rozlytrek

• Allgemeine Beschreibung

  Class: receptor tyrosine kinase; Treatment: NTRK tumors, ROS-1 NSCLC; Other name: RXDX-101; Elimination half-life = 20 h; Protein binding >99%

• Clinical Use

  Entrectinib demonstrated potent antitumor effects in tumor cell lines and patient-derived xenograft (PDX) tumor models in preclinical studies. Furthermore, entrectinib can cross the blood–brain barrier (BBB) to impact primary brain tumors and brain metastases in patients with NTRK1/ NTRK2/NTRK3, ROS1, and ALK fusion-driven cancers.

• in vitro

  entrectinib potently and selectively inhibits the in vitro growth of alk-driven tumors, with confirmed mechanism of action [1].

• in vivo

  since entrectinib is able to pass the blood-brain barrier, the compound was also tested for efficacy in an xenograft model with alk positive nsclc tumors. mri imaging demonstrated that entrectinib was able to effectively and control the growth of these intracranial tumors dose-dependently, leading to increased survival [1].

• target

  Primary targets:TRK, ROS1, ALK

• Einzelnachweise

  [1] elena ardini, maria menichincheri, patrizia banfi, daniele casero, m. laura giorgini, m. beatrice saccardo, nadia amboldi, nilla avanzi, paolo orsini, antonella isacchi, enrico pesenti, arturo galvani. the alk inhibitor nms-e628 also potently inhibits ros1 and induces tumor regression in ros-driven models. [abstract]. in: proceedings of the 104th annual meeting of the american association for cancer research; 2013 apr 6-10; washington, dc. philadelphia (pa): aacr; cancer res 2013;73(8 suppl):abstract nr 2092. doi:10.1158/1538-7445.am2013-2092

Entrectinib Upstream-Materialien And Downstream Produkte

Entrectinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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