5fp3

From Proteopedia

(Difference between revisions)

Revision as of 02:20, 28 January 2016

Cell penetrant inhibitors of the JMJD2 (KDM4) and JARID1 (KDM5) families of histone lysine demethylases

Structural highlights

5fp3 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	5fp4, 5fp7, 5fp8, 5fp9, 5fpa, 5fpb
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[KDM6B_HUMAN] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation.^[1] ^[2]

Publication Abstract from PubMed

Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 </= 100 nM, in KDM4 family biochemical (RFMS) assays with >/=50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 muM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM).

Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives.,Westaway SM, Preston AG, Barker MD, Brown F, Brown JA, Campbell M, Chung CW, Diallo H, Douault C, Drewes G, Eagle R, Gordon L, Haslam C, Hayhow TG, Humphreys PG, Joberty G, Katso R, Kruidenier L, Leveridge M, Liddle J, Mosley J, Muelbaier M, Randle R, Rioja I, Rueger A, Seal GA, Sheppard RJ, Singh O, Taylor J, Thomas P, Thomson D, Wilson DM, Lee K, Prinjha RK J Med Chem. 2016 Jan 15. PMID:26771107^[3]

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

References

↑ De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell. 2007 Sep 21;130(6):1083-94. Epub 2007 Sep 6. PMID:17825402 doi:http://dx.doi.org/S0092-8674(07)01082-3
↑ Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007 Oct 11;449(7163):689-94. Epub 2007 Sep 12. PMID:17851529 doi:http://dx.doi.org/10.1038/nature06192
↑ Westaway SM, Preston AG, Barker MD, Brown F, Brown JA, Campbell M, Chung CW, Diallo H, Douault C, Drewes G, Eagle R, Gordon L, Haslam C, Hayhow TG, Humphreys PG, Joberty G, Katso R, Kruidenier L, Leveridge M, Liddle J, Mosley J, Muelbaier M, Randle R, Rioja I, Rueger A, Seal GA, Sheppard RJ, Singh O, Taylor J, Thomas P, Thomson D, Wilson DM, Lee K, Prinjha RK. Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives. J Med Chem. 2016 Jan 15. PMID:26771107 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01537

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/5fp3"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Cell penetrant inhibitors of the JMJD2 (KDM4) and JARID1 (KDM5) families of histone lysine demethylases==
+<StructureSection load='5fp3' size='340' side='right' caption='[[5fp3]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5fp3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FP3 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3JI:3-(4-PHENYLBUTANAMIDO)PYRIDINE-4-CARBOXYLIC+ACID'>3JI</scene>, <scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fp4|5fp4]], [[5fp7|5fp7]], [[5fp8|5fp8]], [[5fp9|5fp9]], [[5fpa|5fpa]], [[5fpb|5fpb]]</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=5fp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fp3 OCA], [http://pdbe.org/5fp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fp3 RCSB], [http://www.ebi.ac.uk/pdbsum/5fp3 PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/KDM6B_HUMAN KDM6B_HUMAN]] Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation.<ref>PMID:17825402</ref> <ref>PMID:17851529</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Optimization of KDM6B (JMJD3) HTS hit 12 led to the identification of 3-((furan-2-ylmethyl)amino)pyridine-4-carboxylic acid 34 and 3-(((3-methylthiophen-2-yl)methyl)amino)pyridine-4-carboxylic acid 39 that are inhibitors of the KDM4 (JMJD2) family of histone lysine demethylases. Compounds 34 and 39 possess activity, IC50 &lt;/= 100 nM, in KDM4 family biochemical (RFMS) assays with &gt;/=50-fold selectivity against KDM6B and activity in a mechanistic KDM4C cell imaging assay (IC50 = 6-8 muM). Compounds 34 and 39 are also potent inhibitors of KDM5C (JARID1C) (RFMS IC50 = 100-125 nM).
-The entry 5fp3 is ON HOLD
+Cell Penetrant Inhibitors of the KDM4 and KDM5 Families of Histone Lysine Demethylases. 1. 3-Amino-4-pyridine Carboxylate Derivatives.,Westaway SM, Preston AG, Barker MD, Brown F, Brown JA, Campbell M, Chung CW, Diallo H, Douault C, Drewes G, Eagle R, Gordon L, Haslam C, Hayhow TG, Humphreys PG, Joberty G, Katso R, Kruidenier L, Leveridge M, Liddle J, Mosley J, Muelbaier M, Randle R, Rioja I, Rueger A, Seal GA, Sheppard RJ, Singh O, Taylor J, Thomas P, Thomson D, Wilson DM, Lee K, Prinjha RK J Med Chem. 2016 Jan 15. PMID:26771107<ref>PMID:26771107</ref>
-Authors: Chung, C.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Cell penetrant inhibitors of the JMJD2 (KDM4) and JARID1 (KDM5) families of histone lysine demethylases
+<div class="pdbe-citations 5fp3" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Chung, C]]
+[[Category: Inhibitor]]
+[[Category: Jmjd3]]
+[[Category: Jumonji]]
+[[Category: Kdm6b]]
+[[Category: Oxidoreductase]]

5fp3

From Proteopedia

Revision as of 02:20, 28 January 2016

Cell penetrant inhibitors of the JMJD2 (KDM4) and JARID1 (KDM5) families of histone lysine demethylases

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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