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Trk receptor

Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signaling cascades.The common ligands of trk receptors are neurotrophins, a family of growth factors critical to the functioning of the nervous system. The binding of these molecules is highly specific. Each type of neurotrophin has different binding affinity toward its corresponding Trk receptor. The activation of Trk receptors by neurotrophin binding may lead to activation of signal cascades resulting in promoting survival and other functional regulation of cells.

  • Selitrectinib
    T74352097002-61-2
    Selitrectinib (LOXO-195) is a potent and selective inhibitor of the receptor tyrosine kinases(TRK)( TrkA and TrkC with IC50s of 0.6 and <2.5 nM, respectively)
    • $34
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  • Tepotinib
    T61211100598-32-0
    Tepotinib (EMD-1214063) is an inhibitor of MET tyrosine kinase with potential antineoplastic activity.
    • $43
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  • Cyclotraxin B acetate(1203586-72-4 free base)
    TP2068L
    Cyclotraxin B acetate is an antagonist of TrkB receptors; inhibits BDNF-induced TrkB activity (IC50 = 0.30 nM). Allosterically alters TrkB receptor conformation but does not alter BDNF binding. Prevents BDNF-induced cold allodynia in mice. Also shown to exhibit putative anxiolytic properties in mice.
    • $173
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  • ENT-C225
    T733972919962-53-9In house
    ENT-C225 is a potent TrkB neurotrophin receptor (TrkBR) activator with neuroprotective activity for the study of Alzheimer's disease and Parkinson's disease.
    • $195 TargetMol
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  • CG 428
    T412242412055-93-5In house
    CG 428 is a potent tropomyosin receptor Kinase (TRK) Degrader (uSMITETM) with a DC50 of 0.36 nM. CG 428 comprises an analog of the pan-TRK inhibitor GNF-8625 joined by a linker to the cereblon E3 ligase ligand pomalidomide. CG 428 shows selectivity for TRKA over TRKC and TRKB with Kds of 1nM, 4.2 nM, and 28 nM. CG 428 inhibits the growth of KM12 colon cancer cells with an IC50 of 2.9 nM.
    • $178
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  • Trk-IN-4
    T171691799788-94-5In house
    Trk-IN-4 is an effective pan-Trk inhibitor in cell-based assays (IC50s: 1.9 nM, 2.6 nM, and 1.1 nM for TrkA, TrkB, and TrkC, respectively).
      6-8weeks
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    • GNF-8625 monopyridin-N-piperazine hydrochloride
      T400342412055-62-8In house
      GNF-8625 monopyridin-N-piperazine hydrochloride is a protomyosin receptor kinase (TRK) inhibitor.
      • $86
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    • ALE-0540
      T9292234779-34-1In house
      ALE-0540 is a nonpeptidic heterocyclic molecule that inhibits the binding of NGF to p75 and TrkA, as well as signal transduction and biological responses mediated by TrkA receptors.
      • $34
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    • Repotrectinib
      T40711802220-02-5
      Repotrectinib (TPX-0005) is a potent ALK/ROS1/TRK inhibitor, with IC50 of 1.01 nM, 5.3 nM, 1.08 nM and 1.26 nM for WT ALK, SRC, ALK L1196M and ALK G1202R, respectively.
      • $45
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    • Danusertib
      T2094827318-97-8
      Danusertib (PHA-739358) is a small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Danusertib binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed.
      • $54
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    • SP600125
      T3109129-56-6
      SP600125 (JNK Inhibitor II) is a JNK inhibitor that inhibits JNK1, JNK2, and JNK3 (IC50=40/40/90 nM) with oral potency, reversibility, and ATP-competitive properties. SP600125 inhibits autophagy and induces apoptosis.
      • $41
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    • Entrectinib
      T36781108743-60-7
      Entrectinib (RXDX-101) is an inhibitor of TrkA (IC50: 1.7 nM), TrkB (IC50: 0.1 nM), and TrkC (IC50: 0.1 nM), as well as anaplastic lymphoma kinase (ALK; IC50: 1.6 nM) and C-ros oncogene 1 (ROS1; IC50: 0.2 nM). Entrectinib blocks proliferation of ALK-dependent cell lines, including those with C1156Y or L1196M resistance mutations, and inhibits ALK‐dependent signaling. It has been shown to inhibit the growth of a non-small cell lung Y cell line bearing an EML4-ALK rearrangement. In mice bearing various ROS1, Trk, or ALK-driven xenografts, Entrectinib has been shown to induce tumor regression.
      • $35
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    • Multi-kinase-IN-6
      T81740
      Multi-kinase-IN-6 (compound 10e) is a multikinase inhibitor that effectively impedes the activity of TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2. It exhibits antiproliferative effects on MCF7, HCT116, and EKVX cancer cell lines with IC50s of 3.36 μM, 1.40 μM, and 3.49 μM, respectively. Furthermore, Multi-kinase-IN-6 induces cell cycle arrest at the G1/S and G1 phases in MCF7 and HCT116 cells, respectively, and triggers apoptosis effectively [1].
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    • CE-245677
      T14921717899-97-3
      CE-245677 is a potent reversible inhibitor of Tie2 and TrkA/B kinases. With a cellular IC50s of 4.7 and 1 nM.
      • $56
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    • ONO-7475
      T83271646839-59-9
      ONO-7475 is an inhibitor with high specificity for anexelekto and MER tyrosine kinase
      • $57
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    • GNF-5837
      T60971033769-28-6
      GNF-5837 is a specific, and orally bioavailable pan-TRK inhibitor for TrkA/TrkB (IC50: 8/12 nM).
      • $43
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    • TrkA-IN-1
      T132081680179-43-4
      TrkA-IN-1 is a potent and selective inhibitor of Tropomyosin-related kinase A (TrkA) (IC50: 99 nM in a cell-based assay) with analgesic activity.
      • $1,100
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    • 3,5,7,15-Tetraacetoxy-9-nicotinoyloxy-6(17),11-jatrophadien-14-one
      TN2890244277-75-6
      3,5,7,15-Tetraacetoxy-9-nicotinoyloxy-6(17),11-jatrophadien-14-one is a natural product of Euphorbia, Euphorbiaceae. The catalog number is TN2890 and the CAS number is 244277-75-6. 3,5,7,15-Tetraacetoxy-9-nicotinoyloxy-6(17),11-jatrophadien-14-one can be used as a reference standard.
      • $660
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    • TRK II-IN-1
      T730332904690-41-9
      TRK II-IN-1 is a potent type II inhibitor of tropomyosin receptor kinases (TRK), demonstrating inhibitory half-maximal inhibitory concentrations (IC50s) of 3.3, 6.4, 4.3, and 9.4 nM against TRKA, TRKB, TRKC, and the mutant TRKA G667C, respectively. Additionally, this compound exhibits IC50 values of 1.3 nM against FLT3, 9.9 nM against RET, and 71.1 nM against VEGFR2. TRK II-IN-1 primarily serves as a research tool for studying TRK-driven cancers [1].
      • $1,520
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    • Ensartinib hydrochloride
      T223242137030-98-7
      Ensartinib hydrochloride (X-396 dihydrochloride) is a potent new-generation ALK inhibitor with high activity against CNS metastases and a broad range of known crizotinib-resistant ALK mutations. It potently inhibits both wild-type ALK and ALK variants (C1156Y, F1174, G1202R, L1196M, S1206R, and T1151 mutants) with in vitro IC50s of <4 nM.
      • $60
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    • Type II TRK inhibitor 1
      T722892937543-72-9
      Type II TRK Inhibitor 1 is a potent inhibitor targeting multiple tropomyosin receptor kinase (TRK) fusion protein variants as well as the wild type. It demonstrates notable antiproliferative effects on Ba/F3 cells expressing CD74-TRKA G667C and ETV6-TRKC G696C, with half-maximal inhibitory concentrations (IC50s) of 6 nM and 1.7 nM, respectively [1].
      • $1,370
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    • PF-06273340
      T196491402438-74-7
      PF-06273340 is an effective, Selective, and Peripherally Restricted Pan-Trk inhibitor (IC50: Trk-A = 6 nM; Trk-B = 4 nM; Trk-C = 3 nM). PF-06273340 has low metabolic turnover in HLM and hHep is a good substrate for efflux transporters P-gp (ER = 35.7) and BCRP (ER = 4.0) and has moderate passive permeability (RRCK Papp = 5.4 × 10 6 cm s 1).
      • $49
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    • LM22A-4
      T756837988-18-4
      LM22A-4 is a brain-derived neurotrophic factor (BDNF) mimetic and agonist of the receptor tropomyosin-related kinase B (TrkB; IC50 : 47 nM in a fluorescence anisotropy assay)
      • $39
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    • GW 441756
      T6052504433-23-2
      GW 441756 is a specific Tropomyosin-related kinase A (TrkA) inhibitor with an IC50 value of 2 nM.
      • $51
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    • TRK-IN-23
      T789682924344-29-4
      TRK-IN-23 (compound 24b) is a potent, orally active inhibitor of TRK with IC50s of 0.5 nM for TRKA, 9 nM for TRKC, 14 nM for TRKA G595R, 4.4 nM for TRKA F589L, and 4.8 nM for TRKA G667C. It induces apoptosis in Ba/F3-TRKAG595R and Ba/F3-TRKAG667C cells [1].
      • $1,520
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    • Taletrectinib
      T223181505515-69-4
      Taletrectinib (AB-106) is a new-generation selective inhibitor of ROS1/NTRK including ROS1,NTRK1,NTRK2 and NTRK3 with IC50 of 0.207 nM,0.622 nM,2.28 nM and 0.980 nM, respectively.
      • $68
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    • Tavilermide
      T17000263251-78-1
      Tavilermide is a selective and partial agonist of TrkA or a nerve growth factor mimetic.
      • $447
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    • PF-03814735
      T6936942487-16-3
      PF-03814735 is a novel, potent and reversible inhibitor of Aurora A/B with IC50of 0.8 nM/5 nM, is less potent to Flt3, FAK, TrkA, and minimally active to Met and FGFR1. Phase 1.
        5 days
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      • BMS-754807
        T23491001350-96-4
        Dual IGF-1R/InsR Inhibitor BMS-754807 is an oral small molecule inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinases with potential antineoplastic activity.
        • $45
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      • LOXO-195
        T94961350884-56-8
        (6RS)-LOXO-195 (BAY 2731954) is a potent and selective Trk tyrosine kinase inhibitor.
        • $34
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      • Paltimatrectinib
        T624472353522-15-1
        Paltimatrectinib (PBI-200) is a potent tyrosine kinase inhibitor with anticancer activity that inhibits myosin-related kinase A (TrkA).Paltimatrectinib is used in the study of bladder, breast and colorectal cancers.
        • $199
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      • Amitriptyline hydrochloride
        T0678549-18-8
        Amitriptyline hydrochloride (Annoyltin) is the hydrochloride salt of the tricyclic dibenzocycloheptadiene amitriptyline with antidepressant and antinociceptive activities.
        • $45
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      • PF-06737007
        T171701863905-38-7
        PF-06737007 is an effective inhibitor of pan-Trk in cell-based assays (IC50s: 7.7 nM, 15 nM, and 3.9 nM for TrkA, TrkB, and TrkC, respectively).
        • $46
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      • Milciclib
        T6081802539-81-7
        Milciclib (PHA-848125) (PHA-848125) is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Phase 2.
        • $83
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      • Larotrectinib
        T59951223403-58-4
        Larotrectinib (LOXO-101) is an orally administered inhibitor of the TRK kinase and is highly selective only for the TRK family of receptors(IC50s = 2-20 nM).
        • $48
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      • Protein kinase inhibitor 5 sulfate hydrate
        T79126
        Protein kinase inhibitor 5 sulfate hydrate, a potent TRK-A inhibitor, exhibits an IC50 of 1.8 nM and impairs cell viability [1].
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      • N-Acetyl-5-hydroxytryptamine
        T13541210-83-9
        N-Acetyl-5-hydroxytryptamine (O-Demethylmelatonin) , also known as Normelatonin, is the immediate precursor of melatonin. It is produced from serotonin by the enzyme aralkylamine N-acetyltransferase and is converted to melatonin by acetylserotonin O-methyltransferase. It can potently activate TrkB receptor.
        • $32
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      • AZ-23
        T14363915720-21-7
        AZ-23 is an inhibitor of ATP-competitive and Trk kinase A/B/C. For TrkA, TrkB, FGFR1, Flt3, Ret, MuSk, Lck, the IC50s values are 2 nM, 8 nM, 24 nM, 52 nM, 55 nM, 84 nM, 99 nM, respectively.
        • $99
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      • Belizatinib
        T42571357920-84-3
        Belizatinib (TSR-011) is an effective, oral and dual inhibitor of ALK (IC50: 0.7 nM, wild-type recombinant ALK) and TRKA, TRKB, and TRKC.
        • $36
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      • CH7057288
        T56352095616-82-1
        CH7057288 is an effective and selective TRK inhibitor with an IC50 value of 1.1 nM, 7.8 nM and 5.1 nM for TRKA, TRKB and TRKC, respectively.
        • $51
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      • URMC-099
        T60571229582-33-5
        URMC-099 is an orally bioavailable, brain penetrant MLK inhibitor (IC50: 19/42/14/150 nM, for MLK1/MLK2/MLK3/DLK), and also inhibits LRRK2 activity (IC50: 11 nM).
        • $52
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      • Larotrectinib sulfate
        T68801223405-08-0
        Larotrectinib sulfate (LOXO-101 sulfate) is an oral active and specific ATP-competitive inhibitor of tropomyosin receptor kinases (TRK).
        • $33
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      • Tyrphostin AG 879
        T6712148741-30-4
        Tyrphostin AG 879 (AG 879) effectively inhibits HER2/ErbB2 (IC50: 1 μM), 100- and 500-fold higher selective to ErbB2 than EGFR and PDGFR.
        • $43
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      • 7,8-Dihydroxyflavone
        T281638183-03-8
        7,8-Dihydroxyflavone (7,8-DHF) is a naturally-occurring flavone and exist in Tridax procumbens, Godmania aesculifolia, and primula tree leaves.
        • $30
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      • TRK-IN-24
        T797062937544-01-7
        TRK-IN-24 (compound 10g) is a selective inhibitor of Trk receptors, effectively targeting TRKA, TRKC, and mutant forms TRKA G595R, TRKA G667C, and TRKA F589L, with IC50 values of 5.21, 4.51, 6.77, 1.42, and 6.13 nM, respectively. It demonstrates antitumor activity in BaF3-CD74-NTRK1 G595R and BaF3-CD74-NTRK1 G667C xenograft models and inhibits the proliferation of Ba/F3 cells expressing single mutants SF, GK, and xDFG, with an IC50 range of 1.43-47.56 nM [1].
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      • Altiratinib
        T20541345847-93-9
        Altiratinib (DCC-2701)(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with an HGF antagonist in vitro.
        • $48
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      • Protein kinase inhibitor 5
        T791252278204-94-5
        Protein kinase inhibitor 5 is a potent inhibitor of TRK-A, demonstrating an IC50 of 1.8 nM, and effectively suppresses cell viability [1].
        • $1,520
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      • TrkB-IN-1
        T790111609067-49-3
        TrkB-IN-1 is a potent, orally active agonist of the TrkB receptor, with favorable pharmacokinetic (PK) properties. It has been shown to reverse cognitive deficits in an Alzheimer's disease (AD) mouse model, thus serving as a valuable tool for Alzheimer’s disease research [1].
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      • ANA-12
        T2359219766-25-3
        ANA-12 is a potent and selective TrkB antagonist with anxiolytic and antidepressant activity in mice.
        • $34
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      • Diosmetin
        T1704520-34-3
        Diosmetin (Luteolin 4-methyl ether) has been found to act as a weak TrkB receptor agonist.
        • $34
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