Augtyro (repotrectinib)
Research Synopsis
- * It demonstrates potent activity against solvent-front mutations, which often contribute to treatment resistance seen with earlier TKIs like crizotinib and entrectinib.
- * Recent studies highlight its efficacy in overcoming resistance associated with critical mutations, showing promising results in both treatment-naive and previously treated patients.
- * Repotrectinib also exhibits strong anti-tumor effects in neuroblastoma, making it a potential option for high-risk pediatric cases with ALK mutations.
- * Clinical trials indicate that repotrectinib can effectively treat ROS1-rearranged lung cancer, with its ability to cross the blood-brain barrier proving advantageous for patients with brain metastases.
- * Side effects are generally manageable, although some patients report symptoms like weight gain and dizziness related to its action on the nervous system.
- * Pharmacokinetic studies demonstrate the importance of transport proteins in determining the drug's absorption and distribution, affecting its oral availability and therapeutic effectiveness.
- * Ongoing research aims to further explore its combination potential with chemotherapy in various solid tumors to enhance therapeutic outcomes.
- * The resistance profile of repotrectinib suggests a need for ongoing surveillance and adjustment of treatment strategies as new mutations may develop during therapy.
- * Newer compounds and derivative designs aimed at combatting TRK resistance are being investigated, indicating a robust research pipeline around this class of inhibitors.
Augtyro (repotrectinib)
Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.
London, UK
2 hours ago
1 Received
- * A primary cause of resistance is mutations in the kinase domain, particularly solvent-front substitutions involving ALK, ROS1, and TRKC, which are challenging to overcome.
- * Repotrectinib is a next-generation TKI that has shown promise in clinical trials for patients previously treated with other TKIs, effectively targeting and overcoming resistance from these mutations.
$100 - $150
Hourly Rate
CNS metastasis in ROS1+ NSCLC: An urgent call to action, to understand, and to overcome.
London, UK
2 hours ago
1 Received
- The rate of CNS metastasis in patients with advanced ROS1+ NSCLC at diagnosis is largely unknown, but ranges from 20% to mid 30%, and can increase to over 50% during treatment.
- ROS1 fusions are generally considered less aggressive than ALK fusions, contributing to longer progression-free survival in ROS1+ NSCLC patients treated with crizotinib.
- There is an urgent need for more research on the impact of specific ROS1 fusion variants on CNS metastasis and the effectiveness of treatments like pemetrexed for these patients.
$100 - $150
Hourly Rate
Chinese perspectives on clinical efficacy and safety of alectinib in patients with -positive advanced non-small cell lung cancer.
London, UK
2 hours ago
1 Received
- Multiple genetic mutations related to NSCLC have been identified, leading to treatment guidelines that recommend genetic screening to personalize therapy.
- Alectinib, an advanced ALK inhibitor recently approved in China, shows improved efficacy and tolerability against NSCLC, including CNS metastases, compared to earlier treatments like crizotinib.
$100 - $150
Hourly Rate
Targeted therapies for ROS1-rearranged non-small cell lung cancer.
London, UK
2 hours ago
1 Received
- * Crizotinib received FDA approval as a first-line treatment for ROS1+ NSCLC based on its success in extending progression-free survival to an average of 19.2 months in the PROFILE 1001 trial.
- * The emergence of brain metastases and resistance mechanisms to crizotinib has prompted research into new tyrosine kinase inhibitors (TKIs) to improve management of ROS1+ NSCLC.
$100 - $150
Hourly Rate
TRK inhibitors in TRK fusion-positive cancers.
London, UK
2 hours ago
1 Received
- TRK fusions are cancer-causing factors in various cancers, both in adults and children, leading to the development of TRK inhibitors like larotrectinib and entrectinib, which received regulatory approval in 2018 and 2019.
- These first-generation drugs show strong and lasting effects on patients with advanced disease, including those with brain metastases.
- Newer TRK inhibitors like selitrectinib and repotrectinib are designed to combat resistance from mutations and have shown effectiveness in clinical trials, although some side effects like weight gain and dizziness may occur due to their impact on the nervous system.
$100 - $150
Hourly Rate
TRK inhibitors in TRK fusion-positive cancers.
London, UK
2 hours ago
1 Received
- TRK fusions are key drivers of various adult and pediatric cancers, and the first-generation inhibitors, larotrectinib and entrectinib, received significant regulatory approvals in 2018 and 2019 for effective, tumor-agnostic treatment.* -
- Next-generation TRK inhibitors like selitrectinib and repotrectinib have been developed to combat resistance that can arise from mutations in the TRK pathway, and initial clinical results show promise for these drugs.* -
- Although TRK inhibitors generally have a good safety profile, some patients may experience side effects such as weight gain and dizziness due to the impact of these drugs on the TRK pathway related to nervous system functions.*
$100 - $150
Hourly Rate
Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells.
London, UK
2 hours ago
1 Received
- * ALK inhibitors have been used in other cancers and showed promise in treating neuroblastoma, with crizotinib showing modest results, indicating a need for further research.
- * The study explored the third-generation ALK inhibitor repotrectinib, which effectively inhibited ALK signaling and exhibited strong anti-tumor effects in neuroblastoma models, making it a potential treatment option.
$100 - $150
Hourly Rate
The Evolving Diagnostic and Treatment Landscape of NTRK-Fusion-Driven Pediatric Cancers.
London, UK
2 hours ago
1 Received
- The NTRK1-3 genes are important fusion partners in various pediatric cancers, especially in conditions like infantile fibrosarcomas and congenital mesoblastic nephromas.
- Highly selective TRK inhibitors, such as entrectinib and larotrectinib, have shown promising results and are now approved for treating solid tumors with NTRK fusions in children.
- Ongoing developments in second-generation TRK inhibitors and multi-center trials aim to tackle unresolved questions around therapy duration, CNS disease treatment, and long-term effects.
$100 - $150
Hourly Rate
Bioanalytical assay for the new-generation ROS1/TRK/ALK inhibitor repotrectinib in mouse plasma and tissue homogenate using liquid chromatography-tandem mass spectrometry.
London, UK
2 hours ago
1 Received
- Repotrectinib is an advanced drug targeting specific cancers by inhibiting ROS1, TRK, and ALK tyrosine kinases, effectively addressing resistance from certain mutations.
- A new analytical method for measuring repotrectinib in various tissues and mouse plasma was created using liquid chromatography and mass spectrometry, ensuring accurate and efficient results.
- The method was validated with precision and accuracy, allowing it to be used for studying how repotrectinib is processed in the body and its distribution in different tissues in mice.
$100 - $150
Hourly Rate
Cases of ROS1-rearranged lung cancer: when to use crizotinib, entrectinib, lorlatinib, and beyond?
London, UK
2 hours ago
1 Received
- Rearranged (fusion-positive) non-small-cell lung cancer accounts for about 1-2% of cases and is characterized by the activation of the ROS1 tyrosine kinase, leading to the development of targeted therapies.
- FDA-approved drugs crizotinib and entrectinib show high response rates (70-80%) and manageable side effects, with entrectinib having superior efficacy against brain metastases.
- Newer ROS1 TKIs like repotrectinib and DS-6051b demonstrate promising potential in overcoming certain drug resistance mutations, which could improve long-term outcomes for patients with this subtype of lung cancer.
$100 - $150
Hourly Rate
Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naïve and Solvent-Front-Mutant ROS1-Rearranged Non-Small Cell Lung Cancer.
London, UK
2 hours ago
1 Received
- The study investigates the effectiveness of repotrectinib, a new treatment for lung cancer, particularly against the common ROS1-G2032R mutation and brain metastases, which pose therapeutic challenges.
- In preclinical models, repotrectinib showed stronger anti-tumor effects compared to existing treatments like crizotinib and was notably effective at preventing tumor recurrence after treatment cessation.
- Results from an ongoing clinical trial support the potential of repotrectinib as a first-line therapy and for patients who have already progressed on previous ROS1-targeting treatments, demonstrating its ability to penetrate the blood-brain barrier effectively.
$100 - $150
Hourly Rate
Discovery of the Next-Generation Pan-TRK Kinase Inhibitors for the Treatment of Cancer.
London, UK
2 hours ago
1 Received
- * Newer TRK inhibitors, like selitrectinib and repotrectinib, have been created to address the problem of resistance when patients don't respond to initial treatments.
- * Research led to the development of macrocyclic compounds that effectively inhibit both wild-type and mutant forms of the TRK proteins, showing promising results in both chemical activity and pharmacokinetics. *
$100 - $150
Hourly Rate
Targeting TRK: A fast-tracked application of precision oncology and future directions.
London, UK
2 hours ago
1 Received
- - The NTRK genes produce receptor tyrosine kinases TrkA, TrkB, and TrkC, which are crucial for the development and survival of various cell types, influencing synaptic plasticity and pain pathways during embryonic development.
- - Alterations in NTRK genes, often through fusion with other genes, occur in various cancers and lead to the activation of these kinases, contributing to cancer growth; two first-generation TRK inhibitors, larotrectinib and entrectinib, have shown promise in treating these cancers.
- - Despite their effectiveness, resistance to these inhibitors develops over time, prompting the development of second-generation TRK inhibitors like selitrectinib and repotrectin
$100 - $150
Hourly Rate
ABCB1 and ABCG2 Control Brain Accumulation and Intestinal Disposition of the Novel ROS1/TRK/ALK Inhibitor Repotrectinib, While OATP1A/1B, ABCG2, and CYP3A Limit Its Oral Availability.
London, UK
2 hours ago
1 Received
- Repotrectinib is effective against certain cancer types (ROS1/TRK/ALK fusion-positive) in preclinical studies, prompting an investigation into its pharmacokinetics using genetically modified mice.
- The study found that multidrug efflux transporters (ABCB1 and ABCG2) impact repotrectinib's absorption and distribution, with ABCG2 deficiency resulting in higher plasma levels and better brain access.
- Additionally, the OATP1A/1B and CYP3A transport systems also influence how repotrectinib is processed in the body, affecting its oral availability and potentially its therapeutic effectiveness.
$100 - $150
Hourly Rate
Discovery of Next-Generation Tropomyosin Receptor Kinase Inhibitors for Combating Multiple Resistance Associated with Protein Mutation.
London, UK
2 hours ago
1 Received
- TRK inhibition is a promising way to treat various cancers, but resistance often develops due to mutations in specific regions of the TRK protein.
- First-generation TRK inhibitor larotrectinib shows good results, but certain mutations make it less effective, particularly xDFG mutations which resist newer drugs selitrectinib and repotrectinib.
- Researchers have designed a next-generation TRK inhibitor that targets these resistant mutants more effectively, showing better performance in lab models compared to existing treatments.
$100 - $150
Hourly Rate
NTRK fusions in lung cancer: From biology to therapy.
London, UK
2 hours ago
1 Received
- * Next-generation sequencing (NGS) improves the detection of TRK fusions, which can be difficult to diagnose due to complex structural features, emphasizing the potential of RNA-based NGS.
- * First-generation TRK inhibitors like larotrectinib and entrectinib are effective treatments for TRK fusion-positive lung cancers and are generally well tolerated, though monitoring for specific side effects is necessary; new inhibitors are being tested to address resistance issues.
$100 - $150
Hourly Rate
Translational Strategies for Repotrectinib in Neuroblastoma.
London, UK
2 hours ago
1 Received
- Repotrectinib (TPX-0005) is a multikinase inhibitor targeting critical pathways implicated in neuroblastoma, showing potential in treating relapsed or refractory cases.
- In studies, repotrectinib alone demonstrated significant antitumor effects and improved event-free survival compared to control treatments in patient-derived xenograft (PDX) models.
- When combined with chemotherapy, repotrectinib further enhanced antitumor activity across diverse neuroblastoma cell lines, suggesting a promising strategy for clinical application.
$100 - $150
Hourly Rate
Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations.
London, UK
2 hours ago
1 Received
- Chromosomal rearrangements lead to oncogenic TRK fusion proteins that respond to TRK inhibitors like larotrectinib and entrectinib, but resistance mutations limit their effectiveness over time.
- Newer macrocyclic inhibitors such as repotrectinib and selitrectinib are designed to be more effective against mutations that cause resistance, with repotrectinib showing the strongest potency against both wild-type and mutant TRK variants.
- The study includes detailed structural analysis of these inhibitors, highlighting how their unique molecular characteristics influence binding and efficacy, and presents promising results from clinical trials involving repotrectinib in various patient populations.
$100 - $150
Hourly Rate
Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors.
London, UK
2 hours ago
1 Received
- ROS1 fusion proteins are important cancer drivers due to chromosomal rearrangements and can lead to resistance against targeted therapies like entrectinib, lorlatinib, and repotrectinib in non-small cell lung cancer (NSCLC).
- A study using mutagenesis identified the ROS1 mutation as a frequent cause of resistance to entrectinib and lorlatinib, highlighting the challenge of effective treatment.
- ROS1 mutations exhibit broad resistance to type I inhibitors but show sensitivity to type II inhibitors, suggesting that developing selective type II inhibitors or alternating between different types may improve the effectiveness and longevity of treatment.
$100 - $150
Hourly Rate
Pyrizolo[1,5-a]pyrimidine derivatives of the second-generation TRK inhibitor: Design, synthesis and biological evaluation.
London, UK
2 hours ago
1 Received
- Tropomyosin receptor kinase (Trk) is an important target for cancer drugs, especially in treating solid tumors.
- First-generation Trk inhibitors faced limitations due to drug resistance from mutations, but second-generation inhibitors like TPX-0005 offer solutions.
- New compounds, specifically pyrizolo[1,5-a]pyrimidine derivatives, showed promising kinase activity and selectivity against Trk, making them potential alternatives with reduced toxicity compared to TPX-0005.
$100 - $150
Hourly Rate