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 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 (3~{S})-3-[2-[[[1-[(1-methylimidazol-4-yl)methyl]indol-6-yl]methylamino]methyl]-1~{H}-indol-3-yl]-5-oxidanyl-2,3-dihydroisoindol-1-one Ligand Info
Canonical SMILES CN1C=C(N=C1)CN2C=CC3=C2C=C(C=C3)CNCC4=C(C5=CC=CC=C5N4)C6C7=C(C=CC(=C7)O)C(=O)N6
InChI 1S/C31H28N6O2/c1-36-16-21(33-18-36)17-37-11-10-20-7-6-19(12-28(20)37)14-32-15-27-29(24-4-2-3-5-26(24)34-27)30-25-13-22(38)8-9-23(25)31(39)35-30/h2-13,16,18,30,32,34,38H,14-15,17H2,1H3,(H,35,39)/t30-/m0/s1
InChIKey JYEQLXOWWLNVDX-PMERELPUSA-N
PubChem Compound ID 138756246
Drug Binding Sites of Target  Top
PDB ID: 6ZL5      CRYSTAL STRUCTURE OF KRAS-G12D(C118S) IN COMPLEX WITH BI-2852 AND GDP
Method X-ray diffraction Resolution 1.65 Å Mutation Yes [1]
PDB Sequence
GMTEYKLVVV
9
GADGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GSAMRDQYMR
73
TGEGFLCVFA
83
INNTKSFEDI
93
HHYREQIKRV
103

KDSEDVPMVL
113
VGNKSDLPSR
123
TVDTKQAQDL
133
ARSYGIPFIE
143
TSAKTRQGVD
153

DAFYTLVREI
163
RKHK
Residue
Distance (Å)
LYS5
3.692
LEU6
3.633
VAL7
3.505
ASP38
3.475
SER39
2.663
ASP54
2.756
ILE55
4.456
Residue
Distance (Å)
LEU56
3.640
MET67
3.780
GLN70
4.091
TYR71
3.595
THR74
3.622
GLY75
3.943
PDB ID: 6GJ8      CRYSTAL STRUCTURE OF KRAS G12D (GPPCP) IN COMPLEX WITH BI 2852
Method X-ray diffraction Resolution 1.65 Å Mutation Yes [2]
PDB Sequence
GMTEYKLVVV
9
GADGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
CVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKCD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKE
Residue
Distance (Å)
LYS5
3.682
LEU6
3.715
VAL7
3.439
GLU37
2.570
ASP38
4.867
SER39
2.712
ASP54
2.748
Residue
Distance (Å)
ILE55
4.770
LEU56
3.614
MET67
4.613
GLN70
3.717
TYR71
3.476
THR74
3.465
GLY75
3.592
References  Top
REF 1 Drugging all RAS isoforms with one pocket. Future Med Chem. 2020 Nov;12(21):1911-1923.
REF 2 Drugging an undruggable pocket on KRAS. Proc Natl Acad Sci U S A. 2019 Aug 6;116(32):15823-15829.

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