TrkA (TRK1-transforming tyrosine kinase protein) is a protein that in humans is encoded by the NTRK1 gene. TrkA is a member of the neurotrophic tyrosine kinase receptor (NTKR) family. TrkA is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself (autophosphorylation) and members of the MAPK pathway. TrkA is the high affinity catalytic receptor for the neurotrophin, Nerve Growth Factor, which include neuronal differentiation and avoidance of programmed cell death. The presence of TrkA leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in TrkA gene have been associated with congenital insensitivity to pain with anhidrosis, self-mutilating behavior, mental retardation and cancer.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. (TrkA and TrkB also bind NT-3, but to a lesser extent). TrkC is mostly expressed by proprioceptive sensory neurons.
||GNF-5837 is a potent pan-Trk inhibitor which display antiproliferative effects in cellular Ba/F3 assays (IC50 values are 7, 9 and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively).
||LOXO-101 is a small molecule that was designed to block the ATP binding site of the TRK family of receptors, with 2 to 20 nM cellular potency against the TRKA, TRKB, and TRKC kinases.
||GW 441756 is a specific Tropomyosin-related kinase A (TrkA) inhibitor with an IC50 value of 2 nM; little activity to c-Raf1 and CDK2.
||LOXO-101 is a potent, ATP competitive TRK inhibitor with IC50s in low nanomolar range for inhibition of all TRK family members in binding and cellular assays, with 100x selectivity over other kinases, with 2 to 20 nM cellular potency against the TRKA, TRKB, and TRKC kinases.
||PF-06273340 is a highly potent, kinases elective, well-tolerated pan-Trk inhibitor with IC50 values of 6, 4, 3 nM for TrkA, TrkB, Trk C, respectively.
||LM22B-10 is an activator of TrkB/TrkC neurotrophin receptor, and can induce TrkB, TrkC, AKT and ERK activation in vitro and in vivo.