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 T60631 Target Info
Target Name Proto-oncogene c-Ret (RET)
Synonyms RET51; RET receptor tyrosine kinase; RET mutant Y791F; RET mutant V804M; RET mutant V804L; RET mutant S891A; RET mutant M918T; RET mutant G691S; Proto-oncogene tyrosine-protein kinase receptor Ret; PTC; Cadherin family member 12; CDHR16; CDHF12; C-ret
Target Type Successful Target
Gene Name RET
Biochemical Class Kinase
UniProt ID
RET_HUMAN
Ligand General Information  Top
Ligand Name Pralsetinib Ligand Info
Canonical SMILES CC1=CC(=NN1)NC2=NC(=NC(=C2)C)C3CCC(CC3)(C(=O)NC(C)C4=CN=C(C=C4)N5C=C(C=N5)F)OC
InChI 1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19?,27?/m0/s1
InChIKey GBLBJPZSROAGMF-SIYOEGHHSA-N
PubChem Compound ID 129073603
Drug Binding Sites of Target  Top
PDB ID: 7JU5      Structure of RET protein tyrosine kinase in complex with pralsetinib
Method X-ray diffraction Resolution 1.90 Å Mutation No [1]
PDB Sequence
GPLSLSVDAF
709
KILEDPKWEF
719
PRKNLVLGKT
729
LGEGEFGKVV
739
KATAFHLKGR
749

AGYTTVAVKM
759
LKENASPSEL
769
RDLLSEFNVL
779
KQVNHPHVIK
789
LYGACSQDGP
799

LLLIVEYAKY
809
GSLRGFLRES
819
RKVGERALTM
848
GDLISFAWQI
858
SQGMQYLAEM
868

KLVHRDLAAR
878
NILVAEGRKM
888
KISDFGLSRD
898
VYSQGRIPVK
916
WMAIESLFDH
926

IYTTQSDVWS
936
FGVLLWEIVT
946
LGGNPYPGIP
956
PERLFNLLKT
966
GHRMERPDNC
976

SEEMYRLMLQ
986
CWKQEPDKRP
996
VFADISKDLE
1006
KMMVKRR
Residue
Distance (Å)
LEU730
3.644
GLY731
3.454
GLU732
3.612
GLY733
3.384
PHE735
4.752
GLY736
3.576
LYS737
3.363
VAL738
3.558
ALA756
3.243
LYS758
3.638
MET759
3.219
LEU760
3.790
LEU772
3.366
Residue
Distance (Å)
ILE788
4.569
VAL804
3.764
GLU805
2.857
TYR806
3.425
ALA807
2.822
LYS808
3.738
TYR809
4.156
GLY810
3.387
SER811
4.353
ARG878
3.968
LEU881
3.455
SER891
4.704
PDB ID: 7DU9      Crystal structure of human Proto-oncogene tyrosine-protein kinase receptor Ret in complex with Pralsetinib
Method X-ray diffraction Resolution 2.31 Å Mutation No [2]
PDB Sequence
DPKWEFPRKN
723
LVLGKTLGEG
733
EFGKVVKATA
743
FHLKGRAGYT
753
TVAVKMLKEN
763

ASPSELRDLL
773
SEFNVLKQVN
783
HPHVIKLYGA
793
CSQDGPLLLI
803
VEYAKYGSLR
813

GFLRESRKVG
823
PGYLGDERAL
846
TMGDLISFAW
856
QISQGMQYLA
866
EMKLVHRDLA
876

ARNILVAEGR
886
KMKISDFGLS
896
RDVYEEDSYV
906
KRSQGRIPVK
916
WMAIESLFDH
926

IYTTQSDVWS
936
FGVLLWEIVT
946
LGGNPYPGIP
956
PERLFNLLKT
966
GHRMERPDNC
976

SEEMYRLMLQ
986
CWKQEPDKRP
996
VFADISKDLE
1006
KMMVK
Residue
Distance (Å)
LEU730
3.705
GLY731
3.496
GLU732
3.584
GLY733
3.639
PHE735
4.728
GLY736
3.544
LYS737
3.288
VAL738
3.682
ALA756
3.186
LYS758
3.455
MET759
2.900
LEU760
3.691
GLU768
3.764
LEU772
3.173
Residue
Distance (Å)
ILE788
4.370
VAL804
3.727
GLU805
2.745
TYR806
3.513
ALA807
2.745
LYS808
3.867
TYR809
4.170
GLY810
3.359
SER811
4.117
ARG878
3.387
LEU881
3.406
SER891
4.469
ASP892
4.976
References  Top
REF 1 Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations. Ann Oncol. 2021 Feb;32(2):261-268.
REF 2 Selective RET inhibitor TAS0953/HM06

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