TRK-IN-17 is a potent inhibitor of TRK. Tropomyosin-related kinases (Trks) are a family of receptor tyrosine kinases activated by neurotrophins, a group of soluble growth factors including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) and Neurotrophin-4/5 (NT-4/5). TRK-IN-17 has the potential for the research of cancer diseases (extracted from patent WO2021148807A1, compound 3)[1].
Entrectinib is a potent and orally available Trk, ROS1, and ALK inhibitor; inhibits TrkA, TrkB, TrkC, ROS1 and ALK with IC50 values of 1, 3, 5, 12 and 7 nM, respectively.
Larotrectinib (LOXO-101) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).
IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC50 values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies[1].
Altiratinib (DCC-2701) is a multi-targeted kinase inhibitor with IC50s of 2.7, 8, 9.2, 9.3, 0.85, 4.6, 0.83 nM for MET, TIE2, VEGFR2, FLT3, Trk1, Trk2, and Trk3 respectively.
BDNF (human) is a neurotrophin in the central nervous system and mediates survival and differentiation of neurons. BDNF (human) binds to TrkB and leads to the dimerization and autophosphorylation of tyrosine residues in the intracellular domain of the receptor. BDNF (human) can be used for study of neurodegenerative and psychiatric disorder[1][2].
TRK-IN-23 (compound 24b) is a potent and orally active TRK inhibitor with IC50 values of 0.5 nM, 9 nM, 14 nM, 4.4 nM, and 4.8 nM against TRKA, TRKC, TRKAG595R, TRKAF589L, and TRKAG667C, respectively. TRK-IN-23 indues apoptosis of Ba/F3-TRKAG595Rand Ba/F3-TRKAG667C cells[1].
Trk-IN-6 shows excellent in vitro potency on a panel of TRK mutants (IC50 = 0.2-0.7 nM).
CH7057288 is a potent and selective TRK inhibitor.
TRK-IN-24 (compound 10g) is a Trk Receptor inhibitor that inhibits TRKA, TRKC, TRKAG595R, TRKAG667C and TRKAF589L IC50s are 5.21, 4.51, 6.77, 1.42 and 6.13 nM respectively. TRK-IN-24 has antitumor efficacy in BaF3-CD74-NTRK1G595R and BaF3-CD74-NTRK1G667C xenograft models. TRK-IN-24 inhibits the proliferation of Ba/F3 cells transfected with single mutants such as SF, GK, and xDFG, with an IC50 of 1.43-47.56 nM[1].
AZ-23 is an ATP-competitive and orally bioavailable Trk kinase A/B/C inhibitor with IC50s of 2 nM (TrkA), 8 nM (TrkB), 24 nM (FGFR1), 52 nM (Flt3), 55 nM (Ret), 84 nM (MuSk), 99 nM (Lck), respectively.
N-Acetyl-5-hydroxytryptamine is a Melatonin precursor, and that it can potently activate TrkB receptor.
Belizatinib is an oral, dual, potent inhibitor of ALK and TRKA, TRKB, and TRKC, with IC50 of 0.7 nM for wild-type recombinant ALK kinase.
PF-06737007 is a potent pan-Trk inhibitor in cell-based assays with IC50s of 7.7 nM, 15 nM and 3.9 nM for TrkA, TrkB and TrkC, respectively[1]. Anti-hyperalgesic effect[1].
Protein kinase inhibitor 4 (Compound 3) is a protein kinase inhibitor that inhibits TRK-A and ROS1 (IC50=3.0 nM and 104 nM respectively)[1].
TyrphostinAG879 is a tyrosine kinase inhibitor that inhibits TrKA phosphorylation, but not TrKB and TrKC.[1] also a ErbB2 kinase inhibitor, has at least 500-fold higher selectivity to ErbB2 (IC50 = 1 μmol/L) than EGFR (IC50 >500 μmol/L).target: TrKA [1], ErbB2 [2].IC 50: ErbB2 1 μmol/L [2].In vitro: TyrphostinAG879 significantly inhibit the A-type potassium currents in the cultured hippocampus neurons.[2] TyrphostinAG879 can reduce gephyrin puncta in GABAergic neurons and PSD-95 puncta in glutamatergic neurons where ErbB4 expression was low. [3] In vivo: Treatment with TyrphostinAG879 in immunodepressed mice graft with leiomyosarcoma or promyelocytic leukemia cells result in dramatic reductions in tumor sizes. [1]
(3S,4R)-PF-6683324 is a tropomyosin-related kinase (Trk) inhibitor extracted from patent WO2015092610A1 example 9. (3S,4R)-PF-6683324 has the potential for the research of pain and cancer[1].
LM22A-4 is a specific agonist of tyrosine kinase receptor B, used for neurological disease research.
Utatrectinib (AZD-7451) is a potent, selective and orally active Trk inhibitor. Utatrectinib blocks TrkC activation and associated tumorigenic behaviors[1].
Trk-IN-3 is a potent pan-Trk inhibitor in cell-based assays with IC50s of 8.4 nM, 6.2 nM and 2.2 nM for TrkA, TrkB and TrkC, respectively[1]. Anti-hyperalgesic effect[1].
ANA-12 is a potent and selective TrkB antagonist with IC50s of 45.6 nM and 41.1 μM for the high and low affinity sites, respectively.
(3aR)-Selitrectinib ((3aR)-LOXO-195) is an isform of Selitrectinib (HY-101977), which is a next-generation TRK kinase inhibitor, with IC50s of 0.6 nM and <2.5 nM for TRKA and TRKC, respectively[1].
CE-245677 is a potent reversible inhibitor of Tie2 and TrkA/B kinases with a cellular IC50s of 4.7 and 1 nM.
LM22B-10 is an activator of TrkB/TrkC neurotrophin receptor, and can induce TrkB, TrkC, AKT and ERK activation in vitro and in vivo.
LOXO-195 is a next-generation TRK kinase inhibitor (TKI), with IC50s of 0.6 nM, <2.5 nM for TRKA and TRKC respectively.
hTrkA-IN-1 is a potent and orally active inhibitor of TrkA kinase with an IC50 of 1.3 nM, compound 2. extracted from patent WO2015175788. hTrkA-IN-1 can be used for the study of inflammatory disease, such as prostatitis, pelvic, et al[1].
Lestaurtinib (CEP-701;KT-5555) is a multi-kinase inhibitor with potent activity against the Trk family of receptor tyrosine kinases. Lestaurtinib inhibits JAK2, FLT3 and TrkA with IC50s of 0.9, 3 and less than 25 nM, respectively.
Larotrectinib (LOXO-101) sulfate is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).
Repotrectinib (TPX-0005) is a potent ALK/ROS1/TRK inhibitor, with IC50 of 5.3 nM, 1.01 nM, 1.26 nM and 1.08 nM for SRC, WT ALK, ALK G1202R and ALK L1196M, respectively.
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).IC50 Value: 7/9/11 nM (Tel-TrkC/Tel-TrkB/Tel-TrkA) [1]Target: pan-TrkGNF-5837 is an orally bioavailable oxindole compound that and acts as a potent, reversible and type II DFG-out inhibitor of pan-Trk activity (IC50 = 8 and 12 nM for TrkA and TrkB). Shown to target Trk (tropomyosin receptor kinase) ATP binding cleft and an immediately adjacent hydrophobic pocket. Preferentially arrests the proliferation of Ba/F3 cells fused with Tel-TrkA, Tel-TrkB and Tel-TrkC (IC50 = 11, 9 and 7 nM, respectively) and in Ba/F3 and RIE cells expressing both TrkA and NGF (IC50 = 42 and 17 nM, respectively) over Mo7e-c-Kit and Rat-A10-PDGFR (IC50 = 1 and 0.5 μM) and Ba/F3-Tel-KDR and wt-Ba/F3 cells (IC50 = 3.0 and 5.6 μM). GNF-5837 displays ~100-fold greater selectivity among a panel of 59 closely related kinases and in 33 cellular kinase assays. GNF-5837 weakly antagonize relevant cytochrome P450 isozymes and hERG channel, and exhibit adequate microsomal stability, pharmacokinetic profile and efficacy in mice and rats. GNF-5837 suppresses tumor growth in a mouse RIE-TrkAmNGF xenograft model (50 mg/kg, p.o.) [1].