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Compound Detail

CHEMBL4298138

REPOTRECTINIB
💊 Approved Drug
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💊 Approved Drug
C[C@H]1CNC(=O)c2cnn3ccc(nc23)N[C@H](C)c2cc(F)ccc2O1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL4298138
Name REPOTRECTINIB
Phase Approved
Structure Type MOL
InChI Key FIKPXCOQUIZNHB-WDEREUQCSA-N
Therapeutic ✓ Yes

Known Names

Augtyro Repotrectinib TPX-0005 TRX-0005
20
Targets
117
Activities
2
Assay Types
18
PK Parameters
20
Publications
4
Known Names
4
Indications
6
Mechanisms

Molecular Properties

355.4
MW (Da)
2.55
ALogP
6
HBA
2
HBD
80.5
PSA (Ų)
0.65
QED
0
Ro5 Violations
0
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2023
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral
USAN Stem -tinib
USAN Year 2018

Extended Properties

Molecular Formula C18H18FN5O2
MW 355.37
Aromatic Rings 3
Heavy Atoms 26
NP-Likeness -0.53

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Nerve growth factor receptor Trk-A inhibitor INHIBITOR High affinity nerve growth factor receptor ✓ ✓
Neurotrophic tyrosine kinase receptor type 2 inhibitor INHIBITOR BDNF/NT-3 growth factors receptor ✓ ✓
Proto-oncogene tyrosine-protein kinase ROS inhibitor INHIBITOR Proto-oncogene tyrosine-protein kinase ROS ✓ ✓
NT-3 growth factor receptor inhibitor INHIBITOR NT-3 growth factor receptor ✓ ✓
CD74-ROS1 inhibitor INHIBITOR CD74-ROS1 ✓ ✓
ROS1-SDC4 inhibitor INHIBITOR ROS1-SDC4 ✓ ✓

Indications

Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Liver Diseases

ATC Classification

L01EX28
repotrectinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 113 meas. best 11.0
Kd 4 meas. best 10.09

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
NT-3 growth factor receptor
CHEMBL5608
 IC50 11.0 9.7967 0.0 6
Unchecked
CHEMBL612545
 IC50 10.3 9.0092 0.1 12
BDNF/NT-3 growth factors receptor
CHEMBL4898
 IC50 10.3 10.3 0.1 3
Proto-oncogene tyrosine-protein kinase ROS
CHEMBL5568
 IC50 10.15 9.4633 0.1 6
Tyrosine-protein kinase JAK2
CHEMBL2971
 Kd 10.09 10.09 0.1 2
High affinity nerve growth factor receptor
CHEMBL2815
 IC50 9.96 8.8275 0.1 24
BaF3
CHEMBL614524
 IC50 9.18 8.1683 0.7 30
ALK tyrosine kinase receptor
CHEMBL4247
 IC50 9.0 8.55 1.0 14
Tyrosine-protein kinase JAK2
CHEMBL2971
 IC50 8.98 8.98 1.0 3
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
 IC50 8.28 7.8433 5.3 3
ALK tyrosine kinase receptor
CHEMBL4247
 Kd 8.24 8.24 5.7 2
Focal adhesion kinase 1
CHEMBL2695
 IC50 8.16 8.16 7.0 1
EML4-ALK
CHEMBL3883330
 IC50 7.89 7.545 13.0 2
KARPAS-299
CHEMBL2366156
 IC50 7.4 7.4 40.0 1
NCI-H1792
CHEMBL1075525
 IC50 5.72 5.72 1901.0 1
NCI-H2122
CHEMBL1075533
 IC50 5.71 5.71 1936.0 1
NCI-H358
CHEMBL614135
 IC50 5.6 5.6 2500.0 1
NCI-H23
CHEMBL614997
 IC50 5.39 5.39 4059.0 1
NCI-H1373
CHEMBL4296389
 IC50 5.3 5.3 5000.0 1
Cytochrome P450 2C9
CHEMBL3397
 IC50 5.19 5.19 6400.0 1
Cytochrome P450 2C19
CHEMBL3622
 IC50 4.91 4.91 12300.0 1
Cytochrome P450 2D6
CHEMBL289
 IC50 4.54 4.54 28500.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 5330.55 ng.hr.mL-1 Rattus norvegicus
AUC 21222.7 ng.hr.mL-1 Rattus norvegicus
CL 29.0 mL.min-1.kg-1 Homo sapiens
CL 49.0 mL.min-1.kg-1 Rattus norvegicus
CL 982.0 mL.min-1.kg-1 Mus musculus
CL 21.0 mL.min-1.kg-1 Canis lupus familiaris
CL 9.4 mL.min-1.kg-1 Rattus norvegicus
CL 25.6 mL.min-1.g-1 Homo sapiens
Cmax 16900.0 nM Rattus norvegicus
F 119.0 % Rattus norvegicus
Fu 0.05 - Homo sapiens
Fu 0.06 - Rattus norvegicus
Fu 0.05 - Mus musculus
Fu 0.09 - Canis lupus familiaris
T1/2 2.8 hr Rattus norvegicus
T1/2 0.9017 hr Homo sapiens
Tmax 0.8 hr Rattus norvegicus
Vd 1.1 L.kg-1 Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
NT-3 growth factor receptor IC50 = 0.01 nM 11.0 Inhibition of TrKC (unknown origin) incubated for 120 mins in presence of 33P-AT... 34253025
BDNF/NT-3 growth factors receptor IC50 = 0.05 nM 10.3 Inhibition of human TRKB using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-A... 34253025
BDNF/NT-3 growth factors receptor IC50 = 0.05 nM 10.3 Inhibition of TRKB (unknown origin) 36095945
BDNF/NT-3 growth factors receptor IC50 = 0.05 nM 10.3 Inhibition of TRKB (unknown origin) 38183778
Unchecked IC50 = 0.05 nM 10.3 Inhibition of wild type N-terminal 6His-tagged human recombinant TRKB G639R expr... 37413881
Proto-oncogene tyrosine-protein kinase ROS IC50 = 0.07 nM 10.15 Inhibition of human ROS1 using KKKSPGEYVNIEFG as substrate in presence of ATP by... 34253025
Proto-oncogene tyrosine-protein kinase ROS IC50 = 0.07 nM 10.15 Inhibition of ROS1 (unknown origin) 38183778
Proto-oncogene tyrosine-protein kinase ROS IC50 = 0.07 nM 10.15 Inhibition of human ROS1 by discoverX kinome scan assay 37413881
Tyrosine-protein kinase JAK2 Kd = 0.082 nM 10.09 Kinase Binding Assays: Kinase binding assays were performed at DiscoveRx using t... -
Tyrosine-protein kinase JAK2 Kd = 0.082 nM 10.09 Kinase Binding Assays: Kinase binding assays were performed at DiscoveRx using t... -
Unchecked IC50 = 0.1 nM 10.0 Inhibition of wild type N-terminal 6His-tagged human recombinant TRKC G623R muta... 37413881
NT-3 growth factor receptor IC50 = 0.1 nM 10.0 Inhibition of TRKC (unknown origin) 38183778
NT-3 growth factor receptor IC50 = 0.1 nM 10.0 Inhibition of TRKC (unknown origin) 36095945
NT-3 growth factor receptor IC50 = 0.1 nM 10.0 Inhibition of human TRKC using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-A... 34253025
High affinity nerve growth factor receptor IC50 = 0.11 nM 9.96 Inhibition of wildtype human TRKA using poly (Glu,Tyr) 4:1 as substrate in prese... 34303872
Proto-oncogene tyrosine-protein kinase ROS IC50 = 0.17 nM 9.77 Inhibition of ROS1 (unknown origin) incubated for 120 mins in presence of 33P-AT... 34253025
Unchecked IC50 = 0.2 nM 9.7 Inhibition of TRKA F589L mutant (unknown origin) using TK-sub biotin peptide sub... 35486994
High affinity nerve growth factor receptor IC50 = 0.2 nM 9.7 Inhibition of TRKA F589L mutant (unknown origin) preincubated for 30 mins follow... 34668694
Unchecked IC50 = 0.2 nM 9.7 Inhibition of Trk-A F595R mutant (unknown origin) incubated for 30 mins by calip... 33069129
High affinity nerve growth factor receptor IC50 = 0.4 nM 9.4 Inhibition of TRKA G595R mutant (unknown origin) 30188734

Literature References

PubMed DOI Target Context # Activities
37676745 10.1021/acs.jmedchem.3c00899 BaF3 24
34253025 10.1021/acs.jmedchem.1c00712 ADMET 19
34253025 10.1021/acs.jmedchem.1c00712 BaF3 5
34253025 10.1021/acs.jmedchem.1c00712 High affinity nerve growth factor receptor 4
34668694 10.1021/acs.jmedchem.1c01539 High affinity nerve growth factor receptor 4
35486994 10.1016/j.ejmech.2022.114406 High affinity nerve growth factor receptor 4
31419130 10.1021/acs.jmedchem.9b00446 ALK tyrosine kinase receptor 3
34237620 10.1016/j.ejmech.2021.113672 ALK tyrosine kinase receptor 3
37127101 10.1016/j.bmcl.2023.129309 ADMET 3
34303872 10.1016/j.ejmech.2021.113673 Unchecked 3
37210839 10.1016/j.ejmech.2023.115477 BaF3 3
37676745 10.1021/acs.jmedchem.3c00899 High affinity nerve growth factor receptor 3
35486994 10.1016/j.ejmech.2022.114406 Unchecked 2
34253025 10.1021/acs.jmedchem.1c00712 ALK tyrosine kinase receptor 2
37127101 10.1016/j.bmcl.2023.129309 ALK tyrosine kinase receptor 2
30188734 10.1021/acs.jmedchem.8b01092 Unchecked 2
32432477 10.1021/acs.jmedchem.0c00507 Unchecked 2
31419130 10.1021/acs.jmedchem.9b00446 Proto-oncogene tyrosine-protein kinase Src 2
37127101 10.1016/j.bmcl.2023.129309 Unchecked 2
35231576 10.1016/j.bmcl.2022.128646 High affinity nerve growth factor receptor 2

Data from ChEMBL 36 via Core Engine