Target family: Type VII RTKs: Neurotrophin receptor/Trk family (type: catalytic_receptor)
Target: neurotrophic receptor tyrosine kinase 1

Ligand: AZD1332 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.300000190734863 pIC50
Reference (Webpage): AZD1332.

Ligand: CEP-11981 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.520000457763672 pIC50
Reference (Journal): Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): a novel oncology therapeutic agent.
Published in: J Med Chem

Ligand: CH7057288 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.920000076293945 pIC50
Reference (Journal): Discovery of CH7057288 as an Orally Bioavailable, Selective, and Potent pan-TRK Inhibitor.
Published in: J Med Chem

Ligand: compound 1d [PMID: 21493067] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.520000457763672 pIC50
Reference (Journal): In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors.
Published in: Bioorg Med Chem Lett

Ligand: compound 2c [PMID: 24900538] (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 8.850000381469727 pIC50
Reference (Journal): Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors.
Published in: ACS Med Chem Lett

Ligand: CZS-241 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.559999942779541 pIC50
Reference (Journal): Discovery of CZS-241: A Potent, Selective, and Orally Available Polo-Like Kinase 4 Inhibitor for the Treatment of Chronic Myeloid Leukemia.
Published in: J Med Chem

Ligand: D5261 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.539999961853027 pIC50
Reference (Journal): Discovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies.
Published in: Eur J Med Chem

Ligand: D5261 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 5.480000019073486 pIC50
Reference (Journal): Discovery of novel TrkA allosteric inhibitors: Structure-based virtual screening, biological evaluation and preliminary SAR studies.
Published in: Eur J Med Chem

Ligand: DDR1/2 inhibitor 5n (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7 pKd
Reference (Journal): Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2.
Published in: J Med Chem

Ligand: emzeltrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9 pIC50
Reference (Patent): Amino pyrazolopyrimidine compound used as neurotrophic factor tyrosine kinase receptor inhibitor

Ligand: gilteritinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2018), EMA (2019)
Primary target: no
Median affinity: 8.960000038146973 pIC50
Reference (Journal): Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor.
Published in: Blood

Ligand: GNF-5837 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.960000038146973 pIC50
Reference (Journal): Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.
Published in: ACS Med Chem Lett

Ligand: GR-389988 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9.520000457763672 pIC50
Reference (Patent): Tropomyosin-related kinase (Trk) inhibitors

Ligand: GW-2580 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 6.199999809265137 pKd
Reference (Journal): Comprehensive analysis of kinase inhibitor selectivity.
Published in: Nat Biotechnol

Ligand: JNJ-28312141 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.820000171661377 pIC50
Reference (Journal): JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia.
Published in: Mol Cancer Ther

Ligand: K-252a (Natural product)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.889999866485596 pIC50
Reference (Journal): Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a.
Published in: J Med Chem

Ligand: larotrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2018), EMA (2019)
Primary target: no
Median affinity: 8.010000228881836 pIC50
Reference (Patent): Substituted pyrazolo[1,5-a]pyrimidine compounds as TRK kinase inhibitors.

Ligand: milciclib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: yes
Median affinity: 7.28000020980835 pIC50
Reference (Journal): Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor.
Published in: J Med Chem

Ligand: MK-2461 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.340000152587891 pIC50
Reference (Journal): MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor.
Published in: Cancer Res

Ligand: ONO-7579 (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): Pharmacokinetic-Pharmacodynamic-Efficacy Modeling of ONO-7579, a Novel Pan-Tropomyosin Receptor Kinase Inhibitor, in a Murine Xenograft Tumor Model.
Published in: J Pharmacol Exp Ther

Ligand: paltimatrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8 pIC50
Reference (Patent): 5-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(1h-pyrazol-1-yl)pyrazolo[1,5-a]pyrimidine derivatives and related compounds as trk kinase inhibitors for treating cancer

Ligand: ponazuril (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  -
Reference (Journal): Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction.
Published in: Cells

Ligand: repotrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: yes
Approval source: FDA (2023)
Primary target: no
Median affinity: 9.279999732971191 pIC50
Reference (Journal): Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.
Published in: Cancer Discov

Ligand: RIPK1 inhibitor 22b (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 7.590000152587891 pIC50
Reference (Journal): Identification of 5-(2,3-Dihydro-1 H-indol-5-yl)-7 H-pyrrolo[2,3- d]pyrimidin-4-amine Derivatives as a New Class of Receptor-Interacting Protein Kinase 1 (RIPK1) Inhibitors, Which Showed Potent Activity in a Tumor Metastasis Model.
Published in: J Med Chem

Ligand: selitrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9.300000190734863 pIC50
Reference (Patent): Point mutations in trk inhibitor-resistant cancer and methods relating to the same

Ligand: sitravatinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.300000190734863 pIC50
Reference (Journal): Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma.
Published in: Oncotarget

Ligand: taletrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9.210000038146973 pIC50
Reference (Journal): The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models.
Published in: Nat Commun

Ligand: utatrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 8.520000457763672 pIC50
Reference (Patent): 9-(pyrazol-3-yl)-9H-purine-2-amine and 3-(pyrazol-3-yl) -3H-imidazo[4,5-B] pyridin-5-amine derivatives and their use for the treatment of cancer

Ligand: zidesamtinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity:  pKi
Reference (Patent): Heteroaromatic macrocyclic ether chemotherapeutic agents

Ligand: zurletrectinib (Synthetic organic)
Interaction type: Inhibitor
Action: Inhibition
Ligand approved: no
Primary target: no
Median affinity: 9.619999885559082 pIC50
Reference (Patent): Heterocyclic compound as trk inhibitor