Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T28052 | Target Info | |||
| Target Name | Lysine-specific demethylase 5A (KDM5A) | ||||
| Synonyms | Retinoblastoma-binding protein 2; RBP2; RBBP2; RBBP-2; Jumonji/ARID domain-containing protein 1A; JARID1A; Histone demethylase JARID1A | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | KDM5A | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Kdm5A-IN-1 | Ligand Info | |||
| Canonical SMILES | CC(C)C1=CC(=NN1)C(=O)N2CCC(C2)NC(=O)C3CC3 | ||||
| InChI | 1S/C15H22N4O2/c1-9(2)12-7-13(18-17-12)15(21)19-6-5-11(8-19)16-14(20)10-3-4-10/h7,9-11H,3-6,8H2,1-2H3,(H,16,20)(H,17,18)/t11-/m1/s1 | ||||
| InChIKey | CXEXTVGTDZRKJS-LLVKDONJSA-N | ||||
| PubChem Compound ID | 119081409 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5V9T Crystal structure of selective pyrrolidine amide KDM5a inhibitor N-{(3R)-1-[3-(propan-2-yl)-1H-pyrazole-5-carbonyl]pyrrolidin-3-yl}cyclopropanecarboxamide (compound 48) | ||||||
| Method | X-ray diffraction | Resolution | 3.05 Å | Mutation | No | [1] |
| PDB Sequence |
EFVPPPECPV
21 FEPSWEEFTD31 PLSFIGRIRP41 LAEKTGICKI51 RPPKDWQPPF61 ACEVKSFRFT 71 PRVQRLNELE81 AMTRVRLDFL91 DQLAKFWELQ101 GSTLKIPVVE111 RKILDLYALS 121 KIVASKGGFE131 MVTKEKKWSK141 VGSRLGYLPG151 KGTGSLLKSH161 YERILYPYEL 171 FQSGVSLMGV181 QMYTLQSFGE368 MADNFKSDYF378 NMPVHMVPTE388 LVEKEFWRLV 398 SSIEEDVIVE408 YGADISSKDF418 GSGFPVKDGR428 RKILPEEEEY438 ALSGWNLNNM 448 PVLEQSVLAH458 INVDISGMKV468 PWLYVGMCFS478 SFCWHIEDHW488 SYSINYLHWG 498 EPKTWYGVPS508 HAAEQLEEVM518 RELAPELFES528 QPDLLHQLVT538 IMNPNVLMEH 548 GVPVYRTNQC558 AGEFVVTFPR568 AYHSGFNQGY578 NFAEAVNFCT588 ADWLPIGRQC 598 VNHYRRLRRH608 CVFSHEELIF618 KMAADPECLD628 VGLAAMVCKE638 LTLMTEEETR 648 LRESVVQMGV658 LMSEEEVFEL668 VPDDERQCSA678 CRTTCFLSAL688 TCSCNPERLV 698 CLYHPTDLCP708 CPMQKKCLRY718 RYPLEDLPSL728 LYGVKVRAQS738 YDTWVSVMLE 768 DAEDRKYPEN778 DLFRKLR
|
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|
|
GLN75
4.605
TYR409
2.872
GLY410
3.890
ALA411
2.564
ASP412
4.607
MET466
4.789
PRO469
4.841
TRP470
3.150
TYR472
2.196
VAL473
4.385
GLY474
3.514
MET475
4.606
SER478
2.600
SER479
3.750
PHE480
2.297
|
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| PDB ID: 6BH2 LINKED KDM5A JMJ DOMAIN BOUND TO THE INHIBITOR (R)-N-(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropanecarboxamide (Compound N54) | ||||||
| Method | X-ray diffraction | Resolution | 1.45 Å | Mutation | No | [2] |
| PDB Sequence |
AEFVPPPECP
20 VFEPSWEEFT30 DPLSFIGRIR40 PLAEKTGICK50 IRPPKDWQPP60 FACEVKSFRF 70 TPRVQRLNEL80 EAMFGFEREY361 TLQSFGEMAD371 NFKSDYFNMP381 VHMVPTELVE 391 KEFWRLVSSI401 EEDVIVEYGA411 DISSKDFGSG421 FPVKDGRRKI431 LPEEEEYALS 441 GWNLNNMPVL451 EQMKVPWLYV473 GMCFSSFCWH483 IEDHWSYSIN493 YLHWGEPKTW 503 YGVPSHAAEQ513 LEEVMRELAP523 ELFESQPDLL533 HQLVTIMNPN543 VLMEHGVPVY 553 RTNQCAGEFV563 VTFPRAYHSG573 FNQGYNFAEA583 VNFCT
|
|||||
|
|
TYR409
3.492
GLY410
4.101
ALA411
4.523
TRP470
3.891
TYR472
2.986
VAL473
4.794
SER478
4.092
SER479
3.594
PHE480
3.368
HIS483
3.111
GLU485
2.877
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | From a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors. Bioorg Med Chem Lett. 2017 Jul 1;27(13):2974-2981. | ||||
| REF 2 | Insights into the Action of Inhibitor Enantiomers against Histone Lysine Demethylase 5A. J Med Chem. 2018 Apr 12;61(7):3193-3208. | ||||
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