Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | (2S)-3-(3-hydroxyphenyl)-2-(4-iodophenyl)-4-methyl-2H-1-benzopyran-6-ol | Ligand Info | |||
| Canonical SMILES | CC1=C(C(OC2=C1C=C(C=C2)O)C3=CC=C(C=C3)I)C4=CC(=CC=C4)O | ||||
| InChI | 1S/C22H17IO3/c1-13-19-12-18(25)9-10-20(19)26-22(14-5-7-16(23)8-6-14)21(13)15-3-2-4-17(24)11-15/h2-12,22,24-25H,1H3/t22-/m0/s1 | ||||
| InChIKey | RWKXMXMLZHFKIZ-QFIPXVFZSA-N | ||||
| PubChem Compound ID | 137332066 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6DFN Crystal structure of estrogen receptor alpha in complex with receptor degrader 16aa | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
LALSLTADQM
315 VSALLDAEPP325 ILYSEYDPTR335 PFSEASMMGL345 LTNLADRELV355 HMINWAKRVP 365 GFVDLTSHDQ375 VHLLECAWLE385 ILMIGLVWRS395 MEHPGKLLFA405 PNLLLDRNQG 415 KCVEGMVEIF425 DMLLATSSRF435 RMMNLQGEEF445 VCLKSIILLN455 SGVYTFTLKS 468 LEEKDHIHRV478 LDKITDTLIH488 LMAKAGLTLQ498 QQHQRLAQLL508 LILSHIRHMS 518 NKGMEHLYSM528 VVPSYDLLLE542 MLDA
|
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|
|
MET343
4.059
LEU346
3.403
THR347
3.391
LEU349
3.994
ALA350
3.487
ASP351
4.340
GLU353
2.517
TRP383
3.979
LEU384
4.356
LEU387
3.504
MET388
3.848
LEU391
3.870
|
|||||
| PDB ID: 6PET Crystal structure of 8-hydroxychromene compound 30 bound to estrogen receptor alpha | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [2] |
| PDB Sequence |
LALSLTADQM
315 VSALLDAEPP325 ILYSEYDPTR335 PFSEASMMGL345 LTNLADRELV355 HMINWAKRVP 365 GFVDLTSHDQ375 VHLLECAWLE385 ILMIGLVWRS395 MEHPGKLLFA405 PNLLLDRNQG 415 KCVEGMVEIF425 DMLLATSSRF435 RMMNLQGEEF445 VCLKSIILLN455 SGVYTFTLKS 468 LEEKDHIHRV478 LDKITDTLIH488 LMAKAGLTLQ498 QQHQRLAQLL508 LILSHIRHMS 518 NKGMEHLYSM528 KCKNVVPSYD538 LLLEMLDA
|
|||||
|
|
MET343
3.233
LEU346
2.424
THR347
3.012
LEU349
3.437
ALA350
3.029
ASP351
4.507
GLU353
2.859
TRP383
3.312
LEU384
3.662
LEU387
2.914
MET388
3.063
LEU391
3.283
ARG394
2.581
|
|||||
| PDB ID: 7MSA GDC-9545 in complex with estrogen receptor alpha | ||||||
| Method | X-ray diffraction | Resolution | 2.24 Å | Mutation | Yes | [3] |
| PDB Sequence |
LALSLTADQM
315 VSALLDAEPP325 ILYSEYDPTR335 PFSEASMMGL345 LTNLADRELV355 HMINWAKRVP 365 GFVDLTSHDQ375 VHLLECAWLE385 ILMIGLVWRS395 MEHPGKLLFA405 PNLLLDRNQG 415 KCVEGMVEIF425 DMLLATSSRF435 RMMNLQGEEF445 VCLKSIILLN455 SGVYTFTLKS 468 LEEKDHIHRV478 LDKITDTLIH488 LMAKAGLTLQ498 QQHQRLAQLL508 LILSHIRHMS 518 NKGMEHLYSM528 KVVPSYDLLL541 EMLD
|
|||||
|
|
MET343
4.492
LEU346
3.407
THR347
3.221
LEU349
4.146
ALA350
3.585
ASP351
4.241
GLU353
2.569
TRP383
4.066
LEU384
4.359
LEU387
3.494
MET388
3.786
LEU391
3.907
|
|||||
| PDB ID: 6WOK Crystal structure of estrogen receptor alpha in complex with receptor degrader 6 | ||||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | Yes | [4] |
| PDB Sequence |
LALSLTADQM
315 VSALLDAEPP325 ILYSEYDPTR335 PFSEASMMGL345 LTNLADRELV355 HMINWAKRVP 365 GFVDLTSHDQ375 VHLLECAWLE385 ILMIGLVWRS395 MEHPGKLLFA405 PNLLLDRNQG 415 KCVEGMVEIF425 DMLLATSSRF435 RMMNLQGEEF445 VCLKSIILLN455 SGVYTFTLKS 468 LEEKDHIHRV478 LDKITDTLIH488 LMAKAGLTLQ498 QQHQRLAQLL508 LILSHIRHMS 518 NKGMEHLYSM528 PSYDLLLEML544 D
|
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .G9J or .G9J2 or .G9J3 or :3G9J;style chemicals stick;color identity;select .D:343 or .D:346 or .D:347 or .D:349 or .D:350 or .D:351 or .D:353 or .D:383 or .D:384 or .D:387 or .D:388 or .D:391 or .D:394 or .D:404 or .D:421 or .D:424 or .D:425 or .D:428 or .D:521 or .D:524 or .D:525; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
MET343
4.136
LEU346
3.445
THR347
3.704
LEU349
3.950
ALA350
3.602
ASP351
4.427
GLU353
2.998
TRP383
4.178
LEU384
4.273
LEU387
3.452
MET388
3.567
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Unexpected equivalent potency of a constrained chromene enantiomeric pair rationalized by co-crystal structures in complex with estrogen receptor alpha. Bioorg Med Chem Lett. 2019 Apr 1;29(7):905-911. | ||||
| REF 2 | Discovery of a C-8 hydroxychromene as a potent degrader of estrogen receptor alpha with improved rat oral exposure over GDC-0927. Bioorg Med Chem Lett. 2019 Aug 15;29(16):2090-2093. | ||||
| REF 3 | GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer. J Med Chem. 2021 Aug 26;64(16):11841-11856. | ||||
| REF 4 | Discovery of GNE-149 as a Full Antagonist and Efficient Degrader of Estrogen Receptor alpha for ER+ Breast Cancer. ACS Med Chem Lett. 2020 May 26;11(6):1342-1347. | ||||
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