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NTRK Inhibitor Development for Pancreatic Cancer
Alfa Cytology's innovative solutions are designed to support the development of NTRK inhibitors for pancreatic cancer by addressing all phases of the drug development process, providing expertise and resources to facilitate the translation of research results into potential therapeutic agents.
Introduction to NTRK and Its Signaling Pathway
Neurotrophic receptor tyrosine kinase (NTRK) genes, comprising NTRK1, NTRK2, and NTRK3, encode the Trk family of receptor tyrosine kinases: TrkA, TrkB, and TrkC, respectively. These receptors play a crucial role in the development, differentiation, and survival of neurons by binding to neurotrophins such as nerve growth factor (NGF) for TrkA, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) for TrkB, and neurotrophin-3 (NT-3) for TrkC.
Fig. 1 Pathway and function of NTRK gene. (Liu F, et al, 2022)
Upon neurotrophin binding, these receptors dimerize and autophosphorylate, initiating multiple downstream signaling pathways, including the Ras-MAPK pathway, the PI3K-Akt pathway, and the PLCγ pathway, which collectively contribute to neuronal survival, growth, and synaptic plasticity. Dysregulation of NTRK signaling, through gene fusions or mutations, is implicated in various cancers and neurological disorders.
NTRK Inhibitor Development for Pancreatic Cancer
NTRK inhibitors disrupt key downstream signaling pathways by binding to the structural domain of the tyrosine kinase of the Trk receptor, thereby preventing its autophosphorylation and subsequent activation to induce apoptosis, reduce tumor growth, and enhance the efficacy of other therapeutic modalities. The following pipeline drugs are under rigorous investigation to assess their efficacy, safety, and potential to improve the prognosis for pancreatic cancer patients harboring NTRK gene fusions.
| NTRK Inhibitor | Molecular Type | Target | Phase |
|---|---|---|---|
| Larotrectinib (LOXO-101) | Small molecule inhibitor | NTRK1, NTRK2, NTRK3 | Phase II |
| Entrectinib (RXDX-101) | Small molecule inhibitor | NTRK1, NTRK2, NTRK3, ROS1, ALK | Phase II |
| Repotrectinib (TPX-0005) | Small molecule inhibitor | NTRK1, NTRK2, NTRK3, ROS1, ALK | Phase II |
| Taletrectinib (DS-6051b) | Small molecule inhibitor | NTRK1, NTRK2, NTRK3, ROS1 | Phase II |
| Selitrectinib (LOXO-195) | Small molecule inhibitor | NTRK1, NTRK2, NTRK3 | Phase II |
| AZD7451 | Small molecule inhibitor | NTRK1, NTRK2, NTRK3 | Preclinical |
| LOXO-195 | Small molecule inhibitor | NTRK1, NTRK2, NTRK3 | Phase I |
| BAY 2731954 (Vitrakvi) | Small molecule inhibitor | NTRK1, NTRK2, NTRK3 | Phase II |
Our Services
Alfa Cytology's comprehensive services include genomic analysis and identification, in vitro drug screening, cell viability testing, in vivo efficacy studies, mechanism of action studies, pharmacokinetic studies, etc., and customized solutions for the specific needs of researchers aimed at accelerating the development of potent NTRK inhibitors, to address the multiple challenges facing pancreatic cancer research and therapy.
One-Stop NTRK Inhibitor Development Solution
Our NTRK inhibitor development services target the key molecules and pathways associated with pancreatic cancer, developing targeted therapies across multi-molecular types.
They are designed to specifically bind to the TRK proteins encoded by the NTRK genes and inhibit their kinase activity, thereby blocking the downstream signaling pathways that drive cancer cell growth and survival.
TRK-targeted Monoclonal Antibodies
These antibodies can bind to the TRK receptors on the surface of cancer cells, preventing their activation by natural ligands and thus inhibiting downstream signaling.
These conjugates are a combination of a monoclonal antibody specific to TRK receptors and a cytotoxic drug. The antibody component ensures selective delivery of the cytotoxic agent to cancer cells expressing TRK.
These antibodies engage T cells (via CD3) to specifically target and kill TRK-expressing cancer cells, combining the benefits of targeted therapy with immunotherapy.
Why Choose Us?
Tailored Solutions
Our customizable services cater to your specific research needs, ensuring precise and effective solutions.
Advanced Technologies
We employ cutting-edge technologies and methodologies to drive innovative research and accelerate drug discovery.
Proven Track Record
With a history of successful preclinical studies and breakthroughs, we deliver results you can trust.
Specialized Expertise
We specialize in NTRK inhibitor development for pancreatic cancer, offering unmatched knowledge and experience in this field.
Alfa Cytology offers specialized NTRK inhibitor development for pancreatic cancer, leveraging advanced technologies to create effective therapies. Services include genomic profiling, compound screening, and in vivo efficacy studies, etc. The types of molecules developed include small molecule inhibitors, therapeutic antibodies, peptide drug, gene therapy, and more. With a proven track record and tailored solutions, Alfa Cytology is your ideal partner for pioneering cancer research. Contact us to collaborate on innovative therapeutic advancements.
Reference
- Liu F, et al. NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance. Front. Oncol. 2022, 12:864666.
