Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T79031 | Target Info | |||
| Target Name | Beta-secretase 1 (BACE1) | ||||
| Synonyms | Membrane-associated aspartic protease 2; Memapsin-2; KIAA1149; Beta-site amyloid precursor protein cleaving enzyme 1; Beta-site APP cleaving enzyme 1; BACE; Aspartyl protease 2; Asp 2; ASP2 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | BACE1 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | N-[(1S,2R)-1-benzyl-3-{[(1S)-2-(cyclohexylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropyl]-3-(ethylamino)-5-(2-oxopyrrolidin-1-yl)benzamide | Ligand Info | |||
| Canonical SMILES | CCNC1=CC(=CC(=C1)C(=O)NC(CC2=CC=CC=C2)C(CNC(C)C(=O)NC3CCCCC3)O)N4CCCC4=O | ||||
| InChI | 1S/C32H45N5O4/c1-3-33-26-18-24(19-27(20-26)37-16-10-15-30(37)39)32(41)36-28(17-23-11-6-4-7-12-23)29(38)21-34-22(2)31(40)35-25-13-8-5-9-14-25/h4,6-7,11-12,18-20,22,25,28-29,33-34,38H,3,5,8-10,13-17,21H2,1-2H3,(H,35,40)(H,36,41)/t22-,28-,29+/m0/s1 | ||||
| InChIKey | ARWMRRUIIHCDKG-PWUSVURUSA-N | ||||
| PubChem Compound ID | 24882338 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 2VJ6 Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
EMVDNLRGKS
71 GQGYYVEMTV81 GSPPQTLNIL91 VDTGSSNFAV101 GAAPHPFLHR111 YYQRQLSSTY 121 RDLRKGVYVP131 YTQGKWEGEL141 GTDLVSIPHG151 PQVTVRANIA161 AITESDKFFI 171 QGSNWEGILG181 LAYAEIARPD191 DSLEPFFDSL201 VKQTHVPNLF211 SLQLCGGSMI 236 IGGIDHSLYT246 GSLWYTPIRR256 EWYYEVIIVR266 VEINGQDLKM276 DCKEYNYDKS 286 IVDSGTTNLR296 LPKKVFEAAV306 KSIKAASSTE316 KFPDGFWLGE326 QLVCWQAGTT 336 PWNIFPVISL346 YLMGEVTQQS356 FRITILPQQY366 LRPVEDVATS376 QDDCYKFAIS 386 QSSTGTVMGA396 VIMEGFYVVF406 DRARKRIGFA416 VSACHVHDEF426 RTAAVEGPFV 436 TLDMEDCGYN446 I
|
|||||
|
|
SER71
3.964
GLY72
3.510
GLN73
3.618
GLY74
3.505
LEU91
3.653
ASP93
2.598
GLY95
2.967
SER96
3.429
VAL130
3.524
PRO131
3.725
TYR132
3.289
THR133
3.213
GLN134
2.927
PHE169
3.581
ILE171
4.001
|
|||||
| PDB ID: 2XFJ Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
EMVDNLRGKS
71 GQGYYVEMTV81 GSPPQTLNIL91 VDTGSSNFAV101 GAAPHPFLHR111 YYQRQLSSTY 121 RDLRKGVYVP131 YTQGKWEGEL141 GTDLVSIPHG151 PQVTVRANIA161 AITESDKFFI 171 QGSNWEGILG181 LAYAEIARPD191 DSLEPFFDSL201 VKQTHVPNLF211 SLQLCASVGG 233 SMIIGGIDHS243 LYTGSLWYTP253 IRREWYYEVI263 IVRVEINGQD273 LKMDCKEYNY 283 DKSIVDSGTT293 NLRLPKKVFE303 AAVKSIKAAS313 STEKFPDGFW323 LGEQLVCWQA 333 GTTPWNIFPV343 ISLYLMGEVT353 QQSFRITILP363 QQYLRPVEDV373 ATSQDDCYKF 383 AISQSSTGTV393 MGAVIMEGFY403 VVFDRARKRI413 GFAVSACHVH423 DEFRTAAVEG 433 PFVTLDMEDC443 GYNI
|
|||||
|
|
GLY72
3.772
GLN73
3.688
GLY74
3.601
LEU91
3.696
ASP93
2.526
GLY95
2.910
SER96
3.487
VAL130
3.528
PRO131
3.614
TYR132
3.297
THR133
3.259
GLN134
2.990
PHE169
3.610
ILE171
4.070
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character. Bioorg Med Chem Lett. 2008 Feb 1;18(3):1017-21. | ||||
| REF 2 | BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4639-44. | ||||
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