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5kr7

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Revision as of 00:07, 10 September 2016

KDM4C bound to pyrazolo-pyrimidine scaffold

Structural highlights

5kr7 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KDM4C_HUMAN] Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.^[1]

Publication Abstract from PubMed

This communication describes the identification and optimization of a series of pan-KDM5 inhibitors derived from compound 1, a hit initially identified against KDM4C. Compound 1 was optimized to afford compound 20, a 10nM inhibitor of KDM5A. Compound 20 is highly selective for the KDM5 enzymes versus other histone lysine demethylases and demonstrates activity in a cellular assay measuring the increase in global histone 3 lysine 4 tri-methylation (H3K4me3). In addition compound 20 has good ADME properties, excellent mouse PK, and is a suitable starting point for further optimization.

Identification of potent, selective KDM5 inhibitors.,Gehling VS, Bellon SF, Harmange JC, LeBlanc Y, Poy F, Odate S, Buker S, Lan F, Arora S, Williamson KE, Sandy P, Cummings RT, Bailey CM, Bergeron L, Mao W, Gustafson A, Liu Y, VanderPorten E, Audia JE, Trojer P, Albrecht BK Bioorg Med Chem Lett. 2016 Sep 1;26(17):4350-4. doi: 10.1016/j.bmcl.2016.07.026. , Epub 2016 Jul 19. PMID:27476424^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5;125(3):467-81. Epub 2006 Apr 6. PMID:16603238 doi:10.1016/j.cell.2006.03.028
↑ Gehling VS, Bellon SF, Harmange JC, LeBlanc Y, Poy F, Odate S, Buker S, Lan F, Arora S, Williamson KE, Sandy P, Cummings RT, Bailey CM, Bergeron L, Mao W, Gustafson A, Liu Y, VanderPorten E, Audia JE, Trojer P, Albrecht BK. Identification of potent, selective KDM5 inhibitors. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4350-4. doi: 10.1016/j.bmcl.2016.07.026. , Epub 2016 Jul 19. PMID:27476424 doi:http://dx.doi.org/10.1016/j.bmcl.2016.07.026

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5kr7"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5kr7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KR7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6X9:6-ethyl-2,5-dimethyl-7-oxidanylidene-4~{H}-pyrazolo[1,5-a]pyrimidine-3-carbonitrile'>6X9</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6X9:6-ETHYL-2,5-DIMETHYL-7-OXIDANYLIDENE-4~{H}-PYRAZOLO[1,5-A]PYRIMIDINE-3-CARBONITRILE'>6X9</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kr7 OCA], [http://pdbe.org/5kr7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kr7 RCSB], [http://www.ebi.ac.uk/pdbsum/5kr7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kr7 ProSAT]</span></td></tr>
 </table>

5kr7

From Proteopedia

Revision as of 00:07, 10 September 2016

KDM4C bound to pyrazolo-pyrimidine scaffold

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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