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Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity.(1) The common ligands of trk receptors are neurotrophins. Trk receptors dimerize in response to ligand binding. Trk receptors affect neuronal growth and differentiation through the activation of signaling cascades, including PLC, Ras/MAPK, and PI3K. These pathways involve the interception of nuclear and mitochondrial cell-death programs.(2, 3)
The three most common types of trk receptors are trkA, trkB, and trkC. TrkA has the highest affinity to the binding nerve growth factor (NGF). NGF is important in both local and nuclear actions, regulating growth cones, motility, and expression of genes encoding the biosynthesis of enzymes for neurotransmitters. TrkB has the highest affinity to the binding of brain-derived neurotrophic factor (BDNF) and NT-4. BDNF is a growth factor that has important roles in the survival and function of neurons in the central nervous system. The binding of BDNF to TrkB receptor causes many intercellular cascades to be activated, which regulate neuronal development and plasticity, long-term potentiation, and apoptosis. TrkC is ordinarily activated by binding with NT-3 and has little activation by other ligands. TrkC is mostly expressed by proprioceptive sensory neurons.(2, 3)
Trk is activated in 25% of thyroid papillary carcinomas, but was discovered in connection with CRC.(3)

Drugs/Indications
Trial Drugs/Indications
Generic Code Old Code Brand Company Indication trials
AZD7451 AstraZeneca P1: GBM trials
LOXO-101 Loxo P1: solid trials
TSR-011 Tesaro P1/2: solid, lymphoma trials
Failed Drugs
Generic Code Old Code Brand Company Indication trials
AZD6918 AstraZeneca terminated; P1: solid trials


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References

1. Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction*. Annual review of biochemistry. 2003;72(1):609-42.

2. Segal RA. Selectivity in neurotrophin signaling: theme and variations. Annual review of neuroscience. 2003;26(1):299-330.

3. Trk_receptor [cited]; Available from: http://en.wikipedia.org/wiki/Trk_receptor

4. Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nature Reviews Drug Discovery. 2011;10(3):209-19.