Results 191 to 200 of about 2,911,119 (244)

TRK Inhibitors: Clinical Development of Larotrectinib

Current Oncology Reports, 2019
In this review, we highlight the pre-clinical development, recent clinical studies, and future directions of larotrectinib in patients with NTRK fusion-positive tumors.The tropomyosin receptor kinase family, TrkA, TrkB, and TrkC, transmit extracellular signals via a variety of intracellular pathways to promote normal neuronal development.
Munveer S, Bhangoo, Darren, Sigal
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Mechanisms of acquired resistance to TRK inhibitors.

Journal of Clinical Oncology, 2022
3104 Background: First-generation TRK tyrosine kinase inhibitors (TKIs) are approved in a tumor-agnostic fashion in more than 40 countries for patients with NTRK fusion-positive adult and pediatric cancers. While resistance to these agents has previously been described, the exact frequency with which major mechanisms of resistance emerges is not ...
Guilherme Harada, Noura J. Choudhury, Alison M. Schram, Ezra Rosen, Yonina R. Murciano-Goroff, Christina J. Falcon, Clare Wilhelm, Lauren A. Kaplanis, Dazhi Liu, Jason C. Chang, Soo-Ryum Yang, Aradhika Dhawan, Patrick Evans, Casey Savin, Grace Grimaldi, Ronak H. Shah, Emiliano Cocco, Alexander E. Drilon   +17 more
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Research Progress on Small Molecules Inhibitors Targeting TRK Kinases

Current Medicinal Chemistry, 2023
Background: Trk gene fusions are an important driver in the development of cancers, including secretory breast cancer and infantile congenital sarcoma. Since the first-generation of small molecule Trk inhibitors (Larotrectinib and Entrectinib) came to market, research on small molecule TRK inhibitors, especially second-generation inhibi-tors that ...
Ju, Liu, Yadong, Zhang, Yan, Zhu, Lu, Tian, Mingrui, Tang, Jiwei, Shen, Ye, Chen, Shi, Ding   +7 more
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TRK Inhibitors in Non-Small Cell Lung Cancer

Current Treatment Options in Oncology, 2020
Care should be taken to ensure that the diagnostic strategy for a recently diagnosed advanced non-small cell lung cancer includes NTRK fusion testing. RNA sequencing is the gold standard method of detection of NTRK fusion; however, pan-TRK immunohistochemistry could be used as a screening method with good sensitivity.
Guilherme, Harada, Aline Bobato Lara, Gongora, Cesar Martins, da Costa, Fernando Costa, Santini   +3 more
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Outcomes of larotrectinib compared with real-world data from non-TRK inhibitor therapies in patients with TRK fusion cancer: VICTORIA study.

Journal of Clinical Oncology
3105 Background: NTRK gene fusions are oncogenic drivers identified in
M. Brose, C. Westphalen, K. Kehl, Xiaoyun Pan, V. Bernard-Gauthier, M. Kurtinecz, Helen Guo, Virginie Aris, N. R. Brett, Abdelali Majdi, V. Subbiah, N. Pennell, A. Drilon   +12 more
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Abstract CT127: Phase I and expanded access experience of LOXO-195 (BAY 2731954), a selective next-generation TRK inhibitor (TRKi)

Clinical Trials, 2019
Background: Larotrectinib, a selective TRKi, is now FDA approved for pediatric and adult TRK-fusion solid tumors, regardless of tumor origin. Emergent TRK kinase mutations are a common mechanism of resistance to TRKis.
D. Hyman, S. Kummar, A. Farago, B. Geoerger, M. Mau-Sørensen, Matthew H. Taylor, E. Garralda, R. Nagasubramanian, Michael Natheson, Lucy Song, M. Capra, M. Jorgensen, Alan Ho, N. Shukla, Steve Smith, Xin Huang, Brian B. Tuch, N. Ku, T. Laetsch, A. Drilon, D. Hong   +20 more
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Abstract 442: Repotrectinib, a next generation TRK inhibitor, overcomes TRK resistance mutations including solvent front, gatekeeper and compound mutations

Clinical research, 2019
Oncogenic TRKA/B/C fusions are identified in multiple cancer types in adults and children. TRK inhibitors (TRKis) have demonstrated marked efficacy in patients with these cancers, however, acquired on-target resistance mediated by kinase domain mutations
A. Drilon, D. Zhai, W. Deng, Xin Zhang, Dong Lee, E. Rogers, J. Whitten, Zhongdong Huang, A. Graber, Juliet Liu, S. Stopatschinskaja, J. J. Cui, Dong-Wan Kim, Byoung Chul Cho, R. Doebele, Sai-Hong Ignatius Ou, Jeeyun Lee, A. Shaw   +17 more
semanticscholar   +1 more source

Design, synthesis and biological evaluation of macrocyclic derivatives as TRK inhibitors

Bioorganic & Medicinal Chemistry Letters, 2021
Tropomyosin receptor kinases (TRKA, TRKB, TRKC) are transmembrane receptor tyrosine kinases, which are respectively encoded by NTRK1, NTRK2, and NTRK3 genes. Herein, we reported the design, synthesis and Structure-Activity Relationship (SAR) investigation of a series of macrocyclic derivatives as new TRK inhibitors.
Pei, Li, Shi, Cai, Tong, Zhao, Lin, Xu, Dezhong, Guan, Jinruo, Li, Jinpei, Zhou, Huibin, Zhang   +7 more
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Validated HPLC Method for Quantification of a Novel Trk Inhibitor, Larotrectinib in Mice Plasma: Application to a Pharmacokinetic Study

Drug Research, 2020
Larotrectinib, is an orally active novel small molecule approved for the treatment of solid tumors in pediatrics and adult patients. It acts by inhibiting tropomyosin receptor kinase.
H. K. Tripathy, S. V. Nair Manju, Ashok Zakkula, Ram Murthi Bestha, Sreekanth Dittakavi, R. Mullangi   +5 more
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Bayer, Loxo to develop TRK inhibitors

C&EN Global Enterprise, 2017
In a deal worth up to $1.5 billion, Bayer and Loxo Oncology will jointly develop two Loxo drug candidates, larotrectinib and LOXO-195, for treating cancers caused by a rare genetic mutation. Loxo gets $400 million upfront; the remainder of the money is tied to the approval and sale of the two compounds. Larotrectinib and the follow-on compound LOXO-195
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