Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T48598 Target Info
Target Name GTPase KRas (KRAS)
Synonyms c-Ki-ras; c-K-ras; RASK2; Ki-Ras; KRAS2; K-Ras 2
Target Type Clinical trial Target
Gene Name KRAS
Biochemical Class Small GTPase
UniProt ID
RASK_HUMAN
Ligand General Information  Top
Ligand Name 1-[4-[6-chloro-7-(5-methyl-1H-indazol-4-yl)quinazolin-4-yl]piperazin-1-yl]propan-1-one Ligand Info
Canonical SMILES CCC(=O)N1CCN(CC1)C2=NC=NC3=CC(=C(C=C32)Cl)C4=C(C=CC5=C4C=NN5)C
InChI 1S/C23H23ClN6O/c1-3-21(31)29-6-8-30(9-7-29)23-16-10-18(24)15(11-20(16)25-13-26-23)22-14(2)4-5-19-17(22)12-27-28-19/h4-5,10-13H,3,6-9H2,1-2H3,(H,27,28)
InChIKey TWMDOOBUQKHYLW-UHFFFAOYSA-N
PubChem Compound ID 145946084
Drug Binding Sites of Target  Top
PDB ID: 7RP3      Crystal structure of GNE-1952 alkylated KRAS G12C in complex with 2H11 CLAMP
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [1]
PDB Sequence
STEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHK
Residue
Distance (Å)
VAL9
4.291
GLY10
3.453
ALA11
4.695
CYS12
1.839
GLY13
4.712
LYS16
3.057
PRO34
3.336
THR58
3.902
ALA59
3.665
GLY60
3.242
GLN61
3.759
GLU62
3.430
Residue
Distance (Å)
GLU63
3.994
TYR64
3.347
ARG68
3.614
ASP69
2.899
MET72
3.443
HIS95
2.764
TYR96
3.325
GLN99
3.446
ILE100
3.896
ARG102
3.519
VAL103
3.710
PDB ID: 7RP4      Crystal structure of KRAS G12C in complex with GNE-1952
Method X-ray diffraction Resolution 2.15 Å Mutation Yes [1]
PDB Sequence
STEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Residue
Distance (Å)
VAL9
4.140
GLY10
3.388
ALA11
4.189
CYS12
1.814
GLY13
4.700
LYS16
2.974
PRO34
3.292
GLU37
4.409
THR58
4.255
ALA59
3.374
GLY60
3.292
GLN61
3.481
GLU62
3.689
Residue
Distance (Å)
GLU63
3.674
TYR64
3.513
SER65
3.215
ARG68
3.341
ASP69
2.779
MET72
3.495
HIS95
3.207
TYR96
3.258
GLN99
3.457
ILE100
4.360
ARG102
3.144
VAL103
4.229
PDB ID: 6T5V      KRasG12C ligand complex
Method X-ray diffraction Resolution 1.31 Å Mutation No [2]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Residue
Distance (Å)
VAL9
3.285
GLY10
2.788
ALA11
4.038
CYS12
1.816
GLY13
3.918
LYS16
2.879
PRO34
2.511
THR35
4.639
GLU37
4.778
THR58
3.289
ALA59
3.148
GLY60
2.504
GLN61
3.311
Residue
Distance (Å)
GLU62
2.872
GLU63
3.604
TYR64
3.365
ARG68
3.349
ASP69
2.002
MET72
3.273
PHE78
4.385
HIS95
2.792
TYR96
3.116
GLN99
3.279
ILE100
3.054
ARG102
3.093
VAL103
2.831
References  Top
REF 1 Conformation-locking antibodies for the discovery and characterization of KRAS inhibitors. Nat Biotechnol. 2022 May;40(5):769-778.
REF 2 Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS(G12C). J Med Chem. 2020 May 14;63(9):4468-4483.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.