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 Selpercatinib Ligand Info
Canonical SMILES CC(C)(COC1=CN2C(=C(C=N2)C#N)C(=C1)C3=CN=C(C=C3)N4CC5CC(C4)N5CC6=CN=C(C=C6)OC)O
InChI 1S/C29H31N7O3/c1-29(2,37)18-39-24-9-25(28-21(10-30)13-33-36(28)17-24)20-5-6-26(31-12-20)34-15-22-8-23(16-34)35(22)14-19-4-7-27(38-3)32-11-19/h4-7,9,11-13,17,22-23,37H,8,14-16,18H2,1-3H3
InChIKey XIIOFHFUYBLOLW-UHFFFAOYSA-N
PubChem Compound ID 134436906
Drug Binding Sites of Target  Top
PDB ID: 7JU6      Structure of RET protein tyrosine kinase in complex with selpercatinib
Method X-ray diffraction Resolution 2.06 Å Mutation No [1]
PDB Sequence
EDPKWEFPRK
722
NLVLGKTLGE
732
GEFGKVVKAT
742
AFHLKGRAGY
752
TTVAVKMLKE
762

NASPSELRDL
772
LSEFNVLKQV
782
NHPHVIKLYG
792
ACSQDGPLLL
802
IVEYAKYGSL
812

RGFLRESRKV
822
GPGYLGPDER
844
ALTMGDLISF
854
AWQISQGMQY
864
LAEMKLVHRD
874

LAARNILVAE
884
GRKMKISDFG
894
LSRDVYEEDS
904
YVKRSQGRIP
914
VKWMAIESLF
924

DHIYTTQSDV
934
WSFGVLLWEI
944
VTLGGNPYPG
954
IPPERLFNLL
964
KTGHRMERPD
974

NCSEEMYRLM
984
LQCWKQEPDK
994
RPVFADISKD
1004
LEKMMVKR
Residue
Distance (Å)
LEU730
3.627
GLY731
3.482
GLU732
3.785
GLY733
3.780
GLY736
3.449
LYS737
3.044
VAL738
3.603
ALA756
3.459
LYS758
4.104
MET759
3.517
LEU760
4.177
GLU768
3.406
Residue
Distance (Å)
ASP771
4.215
LEU772
3.682
VAL804
4.085
GLU805
3.332
TYR806
3.722
ALA807
3.063
LYS808
3.192
TYR809
3.914
GLY810
3.472
LEU881
3.675
ASP892
3.948
PDB ID: 7DU8      Crystal structure of human Proto-oncogene tyrosine-protein kinase receptor Ret in complex with Selpercatinib
Method X-ray diffraction Resolution 2.75 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
KMMVKR
Residue
Distance (Å)
LEU730
3.883
GLY731
3.632
GLU732
3.923
GLY733
4.228
PHE735
3.384
GLY736
3.628
LYS737
3.410
VAL738
3.296
ALA756
3.275
LYS758
3.709
MET759
3.469
LEU760
3.793
GLU768
3.357
Residue
Distance (Å)
ASP771
3.738
LEU772
3.476
GLU775
4.897
ILE788
4.843
VAL804
4.172
GLU805
3.260
TYR806
3.473
ALA807
3.141
LYS808
3.646
TYR809
3.932
GLY810
3.378
SER811
4.955
LEU881
3.607
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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