Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T07173 Target Info
Target Name Tropomyosin-related kinase A (TrkA)
Synonyms gp140trk; Tyrosine kinase receptor A; Tyrosine kinase receptor; Trk-A; TRKA; TRK1-transforming tyrosine kinase protein; TRK1 transforming tyrosinekinase protein; TRK; P140-TrkA; Neurotrophic tyrosine kinase receptor type 1; NGF-trk receptor type A; MTC; High affinity nerve growth factor receptor
Target Type Successful Target
Gene Name NTRK1
Biochemical Class Kinase
UniProt ID
NTRK1_HUMAN
Ligand General Information  Top
Ligand Name TPX-0005 Ligand Info
Canonical SMILES CC1CNC(=O)C2=C3N=C(C=CN3N=C2)NC(C4=C(O1)C=CC(=C4)F)C
InChI 1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1
InChIKey FIKPXCOQUIZNHB-WDEREUQCSA-N
PubChem Compound ID 135565923
Drug Binding Sites of Target  Top
PDB ID: 7VKN      Crystal structure of TrkA (G595R) kinase with repotrectinib
Method X-ray diffraction Resolution 2.70 Å Mutation Yes [1]
PDB Sequence
GSGIRVHHIK
506
RRDIVLKWEL
516
GEGAFGKVFL
526
AECHNLLPEQ
536
DKMLVAVKAL
546

KEASESARQD
556
FQREAELLTM
566
LQHQHIVRFF
576
GVCTEGRPLL
586
MVFEYMRHRD
596

LNRFLRSHGP
606
DAKLLAGGED
616
VAPGPLGLGQ
626
LLAVASQVAA
636
GMVYLAGLHF
646

VHRDLATRNC
656
LVGQGLVVKI
666
GDFGMRDIYS
677
TDYYRVGGRT
687
MLPIRWMPPE
697

SILYRKFTTE
707
SDVWSFGVVL
717
WEIFTYGKQP
727
WYQLSNTEAI
737
DCITQGRELE
747

RPRACPPEVY
757
AIMRGCWQRE
767
PQQRHSIKDV
777
HARLQALAQA
787
PPVYLDV
Residue
Distance (Å)
LEU516
4.035
GLY517
3.681
GLU518
4.372
VAL524
3.795
ALA542
3.087
LYS544
4.277
VAL573
4.178
PHE589
3.930
GLU590
3.183
TYR591
3.820
Residue
Distance (Å)
MET592
3.014
ARG595
3.457
ASP596
3.730
ARG654
3.007
ASN655
2.891
CYS656
3.565
LEU657
3.379
GLY667
3.260
ASP668
3.280
ARG673
3.583
PDB ID: 7VKO      Crystal structure of TrkA kinase with repotrectinib
Method X-ray diffraction Resolution 2.90 Å Mutation No [1]
PDB Sequence
GSGIRVHHIK
506
RRDIVLKWEL
516
GEGAFGKVFL
526
AECHNLLPEQ
536
DKMLVAVKAL
546

KEASESARQD
556
FQREAELLTM
566
LQHQHIVRFF
576
GVCTEGRPLL
586
MVFEYMRHGD
596

LNRFLRSHGP
606
DAKLLAGGED
616
VAPGPLGLGQ
626
LLAVASQVAA
636
GMVYLAGLHF
646

VHRDLATRNC
656
LVGQGLVVKI
666
GDFGMSRDIY
676
STDYYRVGGR
686
TMLPIRWMPP
696

ESILYRKFTT
706
ESDVWSFGVV
716
LWEIFTYGKQ
726
PWYQLSNTEA
736
IDCITQGREL
746

ERPRACPPEV
756
YAIMRGCWQR
766
EPQQRHSIKD
776
VHARLQALAQ
786
APPVYLD
Residue
Distance (Å)
LEU516
4.037
GLY517
3.703
GLU518
4.543
VAL524
3.596
ALA542
3.214
LYS544
3.968
VAL573
4.084
PHE589
3.886
GLU590
3.224
TYR591
3.699
Residue
Distance (Å)
MET592
2.777
GLY595
3.415
ASP596
3.641
ARG654
3.076
ASN655
3.092
CYS656
3.483
LEU657
3.397
GLY667
3.337
ASP668
3.238
ARG673
3.567
References  Top
REF 1 Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations. Mol Cancer Ther. 2021 Dec;20(12):2446-2456.

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