Tropomyosin receptor kinase inhibitors: an updated patent review for 2016–2019

  title={Tropomyosin receptor kinase inhibitors: an updated patent review for 2016–2019},
  author={Justin J Bailey and Carolin Jaworski and Do Hoang Tung and Carmen W{\"a}ngler and Bj{\"o}rn W{\"a}ngler and Ralf Schirrmacher},
  journal={Expert Opinion on Therapeutic Patents},
  pages={325 - 339}
ABSTRACT Introduction: Tropomyosin receptor kinases (Trks) control processes in the fields of growth, survival, and differentiation of neuronal processes. They also play a crucial role in neurodegenerative diseases as well as different types of cancer. Interest in developing Trk inhibitors to target NTRK fusion-driven cancers has escalated in the last decade, leading to the FDA approval of the pan-Trk inhibitors entrectinib and larotrectinib. The development of next-generation inhibitors that… 
NTRK Fusions and TRK Inhibitors: Potential Targeted Therapies for Adult Glioblastoma
For GBM patients, NTRK fusions and TRK inhibitors are potential target therapy strategy but remain biological mechanism and clinical significance unclarified.
QSAR modelling: a therapeutic patent review 2010-present
The type of compounds described in these types of patents is likely to see an increase in neurodegenerative diseases therapeutics, as the novel methodologies meet the challenging global health needs as human life expectancy increases.
Interplay of BDNF and GDNF in the Mature Spinal Somatosensory System and Its Potential Therapeutic Relevance
This review resumes the current literature on the interplay between BDNF and GDNF in the regulation of nociceptive neurotransmission in the superficial dorsal horn of the spinal cord and discusses the circuitries involved in such a regulation.
Identification and structural analysis of a selective tropomyosin receptor kinase C (TRKC) inhibitor.
Exploring Molecular Docking algorithm for Lung Cancer Drug Discovery – A Case Study with RET Protein
This study focuses on inding the best docking algorithm among ArgusLab, PatchDock, AutoDock 4.0 and AutoD dock Vina for drug discovery process against RET fusion cancers using Pearson’s correlation coef icient.


Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib
In this study, pegcantratinib, 0.5% (wt/wt), applied once daily appeared to be well tolerated and to penetrate the tumor tissue; however, the low tumor drug concentrations demonstrated are likely to account for the lack of response.
Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer
These data confirm the marked tissue-agnostic efficacy and long durability of response in patients with TRK fusion cancer treated with larotrectinib and demonstrate a favorable long-term safety profile.
First-time in-human study of VMD-928, an allosteric and irreversible TrkA selective inhibitor, in patients with solid tumors or lymphoma.
Tropomysin receptor kinase A (TrkA) is a protein encoded by the NTRK1 gene that is oncogenic for multiple tumor types and larotrectinib was treated with chemotherapy in patients with central giant cell granuloma.
Selective TRK Inhibitor CH7057288 against TRK Fusion-Driven Cancer
Members of the tropomyosin receptor kinase (TRK) family are expressed in their constitutively activated forms as a result of a gene fusion that occurs across a wide variety of cancer types. We have
Abstract 788: A novel, potent and selective pan-Trk inhibitor ONO-5390556, demonstrates therapeutic efficacy in cancer cells harboring the TrkA rearrangement
It is suggested that ONO-5390556 may be an effective therapeutic option in a wide variety of cancers including lung and colorectal cancers with Trk rearrangements and demonstrates therapeutic efficacy in cancer cells harboring the TrkA rearrangement.
A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion-Positive Solid Tumors.
LOXO-195 abrogated resistance in TRK fusion-positive cancers that acquired kinase domain mutations, a shared liability with all existing TRK TKIs, establishes a role for sequential treatment by demonstrating continued TRK dependence and validates a paradigm for the accelerated development of next-generation inhibitors against validated oncogenic targets.
Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.
Repotrectinib (TPX-0005) is a rationally designed, low-molecular-weight, macrocyclic TKI that is selective and highly potent against ROS1, TRKA-C, and ALK and may represent an effective therapeutic option for patients with ROS1-, NTRK1-3-, or ALK-rearranged malignancies who have progressed on earlier-generation TKIs.
Abstract 2954A: A potent and selective TRK inhibitor ONO-5390556, shows potent antitumor activity against both TRK-rearranged cancers and the resistant mutants
ONO-5390556 is a highly potent and selective pan-TRK inhibitor with evidence of an excellent anti-tumor activity not only in cancer cells harboring the TRKA rearrangement but also in the two acquired mutations.
TRKing down an old oncogene in a new era of targeted therapy.
The science rationale for the targeting of the TRK oncogene family, which encodes the TRKA, TRKB, and TRKC receptor tyrosine kinases across multiple tumor types, is discussed here.
Efficacy of Larotrectinib in TRK Fusion–Positive Cancers in Adults and Children
Larotrectinib had marked and durable antitumor activity in patients with TRK fusion–positive cancer, regardless of the age of the patient or of the tumor type.