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 | Verubecestat | Ligand Info | |||
| Canonical SMILES | CC1(CS(=O)(=O)N(C(=N1)N)C)C2=C(C=CC(=C2)NC(=O)C3=NC=C(C=C3)F)F | ||||
| InChI | 1S/C17H17F2N5O3S/c1-17(9-28(26,27)24(2)16(20)23-17)12-7-11(4-5-13(12)19)22-15(25)14-6-3-10(18)8-21-14/h3-8H,9H2,1-2H3,(H2,20,23)(H,22,25)/t17-/m0/s1 | ||||
| InChIKey | YHYKUSGACIYRML-KRWDZBQOSA-N | ||||
| PubChem Compound ID | 51352361 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7D2V Crystal Structure of BACE1 in complex with N-{3-[(5R)-3-amino-2,5-dimethyl-1,1-dioxo-5,6-dihydro-2H-1lambda6,2,4-thiadiazin-5-yl]-4-fluorophenyl}-5-fluoropyridine-2-carboxamide | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
RRGSFVEMVD
4 NLRGKSGQGY14 YVEMTVGSPP24 QTLNILVDTG34 SSNFAVGAAP44 HPFLHRYYQR 54 QLSSTYRDLR64 KGVYVPYTQG74 KWEGELGTDL84 VSIPHGPNVT94 VRANIAAITE 104 SDKFFINGSN114 WEGILGLAYA124 EIARPDDSLE134 PFFDSLVKQT144 HVPNLFSLQL 154 CGSVGGSMII176 GGIDHSLYTG186 SLWYTPIRRE196 WYYEVIIVRV206 EINGQDLKMD 216 CKEYNYDKSI226 VDSGTTNLRL236 PKKVFEAAVK246 SIKAASSTEK256 FPDGFWLGEQ 266 LVCWQAGTTP276 WNIFPVISLY286 LMGEVTNQSF296 RITILPQQYL306 RPVEDVATSQ 316 DDCYKFAISQ326 SSTGTVMGAV336 IMEGFYVVFD346 RARKRIGFAV356 SACHVHDEFR 366 TAAVEGPFVT376 LDMEDCGYN
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| PDB ID: 5HU1 BACE1 in complex with (R)-N-(3-(3-amino-2,5-dimethyl-1,1-dioxido-5,6-dihydro-2H-1,2,4-thiadiazin-5-yl)-4-fluorophenyl)-5-fluoropicolinamide | ||||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [2] |
| PDB Sequence |
RGSFVEMVDN
66 LRGKSGQGYY76 VEMTVGSPPQ86 TLNILVDTGS96 SNFAVGAAPH106 PFLHRYYQRQ 116 LSSTYRDLRK126 GVYVPYTQGK136 WEGELGTDLV146 SIPHGPNVTV156 RANIAAITES 166 DKFFINGSNW176 EGILGLAYAE186 IARPDDSLEP196 FFDSLVKQTH206 VPNLFSLQLC 216 GAGFPLNQSE226 VLASVGGSMI236 IGGIDHSLYT246 GSLWYTPIRR256 EWYYEVIIVR 266 VEINGQDLKM276 DCKEYNYDKS286 IVDSGTTNLR296 LPKKVFEAAV306 KSIKAASSTE 316 KFPDGFWLGE326 QLVCWQAGTT336 PWNIFPVISL346 YLMGEVTNQS356 FRITILPQQY 366 LRPVEDSQDD379 CYKFAISQSS389 TGTVMGAVIM399 EGFYVVFDRA409 RKRIGFAVSA 419 CHVHDEFRTA429 AVEGPFVTLD439 MEDCGYNI
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LYS70
4.102
SER71
2.847
GLY72
3.731
GLN73
3.463
GLY74
3.237
TYR75
4.902
LEU91
3.478
ASP93
2.650
GLY95
3.783
SER96
3.740
TYR132
3.250
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective beta-Secretase (BACE1) Inhibitors over BACE2. J Med Chem. 2021 Mar 25;64(6):3075-3085. | ||||
| REF 2 | Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer's Disease. J Med Chem. 2016 Dec 8;59(23):10435-10450. | ||||
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