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 T89534 Target Info
Target Name Estrogen receptor (ESR)
Synonyms Nuclear receptor subfamily 3 group A member 1; NR3A1; Estradiol receptor; ESR; ER-alpha; ER
Target Type Successful Target
Gene Name ESR1
Biochemical Class Nuclear hormone receptor
UniProt ID
ESR1_HUMAN
Ligand General Information  Top
Ligand Name LSZ102 Ligand Info
Canonical SMILES CC(C1=C(C=CC(=C1)F)C2=C(C3=C(S2)C=C(C=C3)O)OC4=CC=C(C=C4)C=CC(=O)O)(F)F
InChI 1S/C25H17F3O4S/c1-25(27,28)20-12-15(26)5-9-18(20)24-23(19-10-6-16(29)13-21(19)33-24)32-17-7-2-14(3-8-17)4-11-22(30)31/h2-13,29H,1H3,(H,30,31)/b11-4+
InChIKey SJXNPGGVGZXKKI-NYYWCZLTSA-N
PubChem Compound ID 118574930
Drug Binding Sites of Target  Top
PDB ID: 6V8T      Estrogen Receptor Alpha Ligand Binding Domain Y537S in Complex with LSZ102
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [1]
PDB Sequence
MALSLTADQM
315
VSALLDAEPP
325
ILYSEYASMM
343
GLLTNLADRE
353
LVHMINWAKR
363

VPGFVDLTLH
373
DQVHLLESAW
383
LEILMIGLVW
393
RSMEHPGKLL
403
FAPNLLLDRN
413

QGEGMVEIFD
426
MLLATSSRFR
436
MMNLQGEEFV
446
CLKSIILLNS
456
GVYTFKDHIH
476

RVLDKITDTL
486
IHLMAKAGLT
496
LQQQHQRLAQ
506
LLLILSHIRH
516
MSNKGMEHLY
526

SSDLLLEMLD
545
Residue
Distance (Å)
MET343
3.938
LEU346
3.218
THR347
3.452
LEU349
4.235
ALA350
3.633
GLU353
2.864
TRP383
4.259
LEU384
4.142
LEU387
3.434
MET388
4.134
LEU391
3.937
ARG394
3.266
Residue
Distance (Å)
LEU402
4.867
PHE404
3.266
MET421
3.766
ILE424
3.160
PHE425
4.334
LEU428
3.258
LYS520
4.160
GLY521
3.085
MET522
4.989
HIS524
3.705
LEU525
3.786
PDB ID: 6B0F      ESTROGEN RECEPTOR ALPHA LIGAND BINDING DOMAIN IN COMPLEX WITH LSZ102
Method X-ray diffraction Resolution 2.86 Å Mutation Yes [2]
PDB Sequence
SLTADQMVSA
318
LLDAEPPILY
328
SSEASMMGLL
346
TNLADRELVH
356
MINWAKRVPG
366

FVDLTLHDQV
376
HLLESAWLEI
386
LMIGLVWRSM
396
EHPGKLLFAP
406
NLLLDVEGMV
422

EIFDMLLATS
432
SRFRMMNLQG
442
EEFVCLKSII
452
LLNSGHIHRV
478
LDKITDTLIH
488

LMAKAGLTLQ
498
QQHQRLAQLL
508
LILSHIRHMS
518
NKGMEHLYKS
530
KNVVPLYDLL
540

LEML
Residue
Distance (Å)
MET343
3.721
LEU346
3.495
THR347
3.372
LEU349
3.607
ALA350
3.925
GLU353
2.669
TRP383
4.309
LEU384
4.084
LEU387
3.424
MET388
3.748
LEU391
3.794
ARG394
3.087
LEU402
4.638
Residue
Distance (Å)
PHE404
3.114
MET421
3.472
ILE424
3.400
PHE425
3.681
LEU428
3.159
GLY521
3.640
HIS524
3.100
LEU525
3.654
TYR526
2.963
SER530
4.159
LYS531
3.685
ASN532
2.758
VAL533
3.103
References  Top
REF 1 Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in ESR1 mutant breast cancer cells. Elife. 2022 May 16;11:e72512.
REF 2 Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. J Med Chem. 2018 Apr 12;61(7):2837-2864.

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