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 T40474 Target Info
Target Name Proto-oncogene c-Met (MET)
Synonyms Tyrosine-protein kinase Met; Scatter factor receptor; SF receptor; Met proto-oncogene tyrosine kinase; Hepatocyte growth factor receptor; HGF/SF receptor; HGF-SF receptor; HGF receptor; C-met; C-Met receptor tyrosine kinase
Target Type Successful Target
Gene Name MET
Biochemical Class Kinase
UniProt ID
MET_HUMAN
Ligand General Information  Top
Ligand Name SAR125844 Ligand Info
Canonical SMILES C1COCCN1CCNC(=O)NC2=NC3=C(S2)C=C(C=C3)SC4=NN=C5N4N=C(C=C5)C6=CC=C(C=C6)F
InChI 1S/C25H23FN8O2S2/c26-17-3-1-16(2-4-17)19-7-8-22-30-31-25(34(22)32-19)37-18-5-6-20-21(15-18)38-24(28-20)29-23(35)27-9-10-33-11-13-36-14-12-33/h1-8,15H,9-14H2,(H2,27,28,29,35)
InChIKey ODIUNTQOXRXOIV-UHFFFAOYSA-N
PubChem Compound ID 25182860
Drug Binding Sites of Target  Top
PDB ID: 5HO6      CRYSTAL STRUCTURE OF CMET IN COMPLEX WITH CMPD.
Method X-ray diffraction Resolution 1.97 Å Mutation Yes [1]
PDB Sequence
VQAVQHVVIG
1072
PCVYHGTLIH
1106
CAVKSVSQFL
1125
TEGIIMKDFS
1135
HPNVLSLLGI
1145

CGSPLVVLPY
1159
MKHGDLRNFI
1169
RNETHNPTVK
1179
DLIGFGLQVA
1189
KGMKFLASKK
1199

FVHRDLAARN
1209
CMLDEKFTVK
1219
VADFGLARLP
1246
VKWMALESLQ
1256
TQKFTTKSDV
1266

WSFGVLLWEL
1276
MTRGAPPYPD
1286
VNTFDITVYL
1296
LQGRRLLQPE
1306
YCPDPLYEVM
1316

LKCWHPKAEM
1326
RPSFSELVSR
1336
ISAIFSTFIG
1346
EHYVHVNATY
1356
Residue
Distance (Å)
VAL1092
3.780
ALA1108
3.516
LEU1140
3.846
LEU1157
3.514
PRO1158
3.291
TYR1159
3.207
MET1160
2.572
LYS1161
3.290
HIS1162
3.502
Residue
Distance (Å)
GLY1163
3.471
ASP1164
3.282
ASN1167
4.270
ARG1208
3.667
ASN1209
4.215
MET1211
3.370
ALA1221
3.812
ASP1222
3.445
ALA1226
3.150
PDB ID: 5HOA      Crystal structure of c-Met L1195V in complex with SAR125844
Method X-ray diffraction Resolution 2.14 Å Mutation No [1]
PDB Sequence
AVQHVVVYHG
1095
TLKIHCAVKQ
1123
FLTEGIIMKD
1133
FSHPNVLSLL
1143
GVLPYMKHGD
1164

LRNFIRNETH
1174
NPTVKDLIGF
1184
GLQVAKGMKF
1194
VASKKFVHRD
1204
LAARNCMLDE
1214

KFTVKVADFG
1224
LARLPVKWMA
1251
LESLQTQKFT
1261
TKSDVWSFGV
1271
LLWELMTRGA
1281

PPYPDVNTFD
1291
ITVYLLQGRR
1301
LLQPEYCPDP
1311
LYEVMLKCWH
1321
PKAEMRPSFS
1331

ELVSRISAIF
1341
STFIGEHYVH
1351
VNATY
Residue
Distance (Å)
VAL1092
3.940
ALA1108
4.008
LEU1140
4.157
LEU1157
3.582
PRO1158
3.785
TYR1159
3.115
MET1160
2.585
LYS1161
3.162
HIS1162
4.224
GLY1163
3.649
Residue
Distance (Å)
ASP1164
3.431
ASN1167
3.428
ASN1171
4.845
ARG1208
3.167
ASN1209
3.843
CYS1210
4.942
MET1211
3.398
ALA1221
3.364
ASP1222
3.017
ALA1226
3.382
PDB ID: 5HOR      Crystal structure of c-Met-M1250T in complex with SAR125844.
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [1]
PDB Sequence
QAVQHVVIGP
1073
GCVYHGTLKI
1105
HCAVKSVSQF
1124
LTEGIIMKDF
1134
SHPNVLSLLG
1144

ICLRSEGSPL
1154
VVLPYMKHGD
1164
LRNFIRNETH
1174
NPTVKDLIGF
1184
GLQVAKGMKF
1194

LASKKFVHRD
1204
LAARNCMLDE
1214
KFTVKVADFG
1224
LARDMLPVKW
1249
TALESLQTQK
1259

FTTKSDVWSF
1269
GVLLWELMTR
1279
GAPPYPDVNT
1289
FDITVYLLQG
1299
RRLLQPEYCP
1309

DPLYEVMLKC
1319
WHPKAEMRPS
1329
FSELVSRISA
1339
IFSTFIGEHY
1349
VHVNATY
Residue
Distance (Å)
VAL1092
3.686
ALA1108
3.595
LEU1140
4.100
LEU1157
3.648
PRO1158
3.567
TYR1159
2.975
MET1160
2.668
LYS1161
3.266
HIS1162
3.644
GLY1163
3.502
Residue
Distance (Å)
ASP1164
3.180
ASN1167
3.624
ARG1208
3.489
ASN1209
3.991
MET1211
3.037
ALA1221
3.370
ASP1222
2.904
PHE1223
4.866
ALA1226
3.231
References  Top
REF 1 Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]benzothiazol-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844). J Med Chem. 2016 Aug 11;59(15):7066-74.

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