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 T58970 Target Info
Target Name Extracellular signal-regulated kinase 2 (ERK2)
Synonyms PRKM2; PRKM1; P42-MAPK; P42 Mitogen-activated protein kinase; Mitogen-activated protein kinase 2; Mitogen-activated protein kinase 1; MAPK 2; MAPK 1; MAP kinase isoform p42; MAP kinase 2; MAP kinase 1; ERT1; ERK-2
Target Type Clinical trial Target
Gene Name MAPK1
Biochemical Class Kinase
UniProt ID
MK01_HUMAN
Ligand General Information  Top
Ligand Name GDC-0994 Ligand Info
Canonical SMILES CN1C(=CC=N1)NC2=NC=CC(=N2)C3=CC(=O)N(C=C3)C(CO)C4=CC(=C(C=C4)Cl)F
InChI 1S/C21H18ClFN6O2/c1-28-19(5-8-25-28)27-21-24-7-4-17(26-21)13-6-9-29(20(31)11-13)18(12-30)14-2-3-15(22)16(23)10-14/h2-11,18,30H,12H2,1H3,(H,24,26,27)/t18-/m1/s1
InChIKey RZUOCXOYPYGSKL-GOSISDBHSA-N
PubChem Compound ID 71727581
Drug Binding Sites of Target  Top
PDB ID: 6OPH      phosphorylated ERK2 with GDC-0994
Method X-ray diffraction Resolution 2.40 Å Mutation No [1]
PDB Sequence
PEMVRGQVFD
18
VGPRYTNLSY
28
IGEGAYGMVC
38
SAYDNVNKVR
48
VAIKKISPFE
58

HQTYCQRTLR
68
EIKILLRFRH
78
ENIIGINDII
88
RAPTIEQMKD
98
VYIVQDLMET
108

DLYKLLKTQH
118
LSNDHICYFL
128
YQILRGLKYI
138
HSANVLHRDL
148
KPSNLLLNTT
158

CDLKICDFGL
168
ARVADPDHDH
178
TGFLEVATRW
190
YRAPEIMLNS
200
KGYTKSIDIW
210

SVGCILAEML
220
SNRPIFPGKH
230
YLDQLNHILG
240
ILGSPSQEDL
250
NCIINLKARN
260

YLLSLPHKNK
270
VPWNRLFPNA
280
DSKALDLLDK
290
MLTFNPHKRI
300
EVEQALAHPY
310

LEQYYDPSDE
320
PIAEAPFKFD
330
MELDDLPKEK
340
LKELIFEETA
350
RFQPGY
Residue
Distance (Å)
ILE29
3.651
GLY30
4.078
GLU31
3.394
GLY32
3.597
ALA33
4.784
TYR34
4.492
GLY35
3.683
MET36
3.826
VAL37
3.025
ALA50
3.233
LYS52
3.234
LYS53
4.998
GLU69
4.685
ILE82
4.663
Residue
Distance (Å)
GLN103
3.535
ASP104
3.260
LEU105
3.839
MET106
2.704
GLU107
2.979
THR108
3.860
ASP109
3.606
LYS112
3.750
SER151
3.562
ASN152
2.401
LEU154
3.550
CYS164
3.959
ASP165
3.215
PDB ID: 5K4I      Crystal Structure of ERK2 in complex with compound 22
Method X-ray diffraction Resolution 1.76 Å Mutation No [2]
PDB Sequence
AGPEMVRGQV
18
FDVGPRYTNL
28
SYIGEGAYGM
38
VCSAYDNVNK
48
VRVAIKKISP
58

FEHQTYCQRT
68
LREIKILLRF
78
RHENIIGIND
88
IIRAPTIEQM
98
KDVYIVQDLM
108

ETDLYKLLKT
118
QHLSNDHICY
128
FLYQILRGLK
138
YIHSANVLHR
148
DLKPSNLLLN
158

TTCDLKICDF
168
GLARVADTRW
192
YRAPEIMLNS
202
KGYTKSIDIW
212
SVGCILAEML
222

SNRPIFPGKH
232
YLDQLNHILG
242
ILGSPSQEDL
252
NCIINLKARN
262
YLLSLPHKNK
272

VPWNRLFPNA
282
DSKALDLLDK
292
MLTFNPHKRI
302
EVEQALAHPY
312
LEQYYDPSDE
322

PIAEAPFKFD
332
MELDDLPKEK
342
LKELIFEETA
352
RFQPGY
Residue
Distance (Å)
ILE31
3.628
GLY32
3.622
GLU33
3.272
GLY34
3.263
ALA35
4.868
TYR36
4.690
GLY37
3.037
MET38
3.551
VAL39
3.419
ALA52
3.279
LYS54
3.229
LYS55
4.898
GLU71
4.109
ILE84
4.575
Residue
Distance (Å)
GLN105
3.561
ASP106
3.175
LEU107
3.928
MET108
2.841
GLU109
3.380
THR110
3.811
ASP111
3.496
LYS114
2.880
SER153
4.018
ASN154
2.671
LEU156
3.475
CYS166
3.729
ASP167
2.869
References  Top
REF 1 Activation loop dynamics are controlled by conformation-selective inhibitors of ERK2. Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15463-15468.
REF 2 Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development. J Med Chem. 2016 Jun 23;59(12):5650-60.

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