GSK-J4 1.5μM R08 exp441

JMJD3/KDM6B, UTX/KDM6A histone demethylase inhibitor (H3K27me2/me3)

Class / Subclass 1: Gene Regulation / Epigenetic Inhibitor

Compound References

PubChem Name: GSK J4 HCl
Synonyms: N/A
CAS #: 1797983-09-5
PubChem CID: 71729974
IUPAC: ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate;hydrochloride
INCHI Name: InChI=1S/C24H27N5O2.ClH/c1-2-31-23(30)10-14-26-21-17-22(28-24(27-21)20-9-5-6-13-25-20)29-15-11-18-7-3-4-8-19(18)12-16-29;/h3-9,13,17H,2,10-12,14-16H2,1H3,(H,26,27,28);1H
INCHI Key: TYXWLTBYINKVNT-UHFFFAOYSA-N
Molecular Weight: 454
Canonical SMILES: CCOC(=O)CCNC1=CC(=NC(=N1)C2=CC=CC=N2)N3CCC4=CC=CC=C4CC3.Cl
Isomeric SMILES: N/A
Molecular Formula: C24H28ClN5O2

Compound Supplier

Supplier Name: Sigma-Aldrich
Catalog #: SML0701
Lot #: 053M4601V

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C24H27N5O2 418.22375; found 418.22478

Dose Response Curve

Platform ID: GSK-J4
Min: -0.8548; Max: 90.3053

IC	Concentration (µM)
IC10	N/A
IC20	0.5053
IC30	0.6250
IC40	0.7484
IC50	0.8887
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 08
Dose: 1.5µM
Days of incubation: 8
Doublings: 0.7
Numbers of reads: 17884362

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
1/58	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
ZBTB7A	-3.12	<0.01
ESPL1	-3.03	0.41
NPIPB8	-2.95	0.24
ATP6AP1	-2.78	0.12
CFAP45	-2.75	0.41
SCAF1	-2.65	0.41
OTUB1	-2.58	0.12
RSRC2	-2.56	0.51
RPL38	-2.49	0.24
BCAM	-2.47	0.12
CPSF6	-2.46	0.12
DVL3	-2.32	0.19
CABLES1	-2.29	0.31
CCDC146	-2.27	0.22
AURKB	-2.26	0.51
RPS11	-2.24	0.41
CCDC83	-2.23	0.27
MTRNR2L3	-2.22	0.55
COL21A1	-2.22	0.27
PELP1	-2.21	0.41
MEMO1	-2.19	0.24
ITK	-2.17	0.24
ESYT1	-2.16	0.24
MYL2	-2.15	0.31
PARK7	-2.14	0.25
CFLAR	-2.10	0.27
CNOT2	-2.07	0.29
IGBP1	-2.07	0.46
TMEM230	-2.07	0.41
LRR1	-2.06	0.47
MARCH5	2.59	<0.01
TAMM41	2.61	<0.01
MRPS23	2.62	<0.01
TEFM	2.66	<0.01
MBTPS2	2.67	0.01
CEPT1	2.67	<0.01
TFAM	2.70	0.02
MRP63	2.72	0.02
CASP9	2.75	<0.01
RPIA	2.77	<0.01
KIAA0391	2.79	<0.01
RPUSD4	2.85	<0.01
MTPAP	2.86	<0.01
MRPL21	2.90	<0.01
TP53	2.93	<0.01
YARS2	2.93	<0.01
MRPS14	2.99	<0.01
MRPL23	3.05	<0.01
COX5A	3.08	<0.01
GSTO1	3.16	0.00
DARS2	3.20	<0.01
CYCS	3.26	0.00
MRPS18A	3.31	0.00
BAK1	3.65	0.00
SUPV3L1	3.70	0.00
APAF1	3.79	0.00
HSD17B10	4.10	0.00
HCCS	4.60	0.00
STARD7	5.41	0.00
SLC39A10	8.50	0.00

Screen	Correlation	Plot
Hydroxyurea 100μM R07 exp329	0.127	View
Tanespimycin 14μM R08 exp527	0.117	View
ONC212 0.15μM R08 exp513	0.111	View
TIC10 10μM R08 exp532	0.111	View
PU-H71 1μM R08 exp515	0.097	View
Mitomycin-C 0.06μM R08 exp503	0.096	View
Thimerosal 0.85μM R08 exp529	0.093	View
UM0125461 0.74μM R02 exp84	0.066	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.061	View
Hippuristanol 0.12μM R08 exp488	0.061	View
THZ1 0.06μM R08 exp531	0.057	View
JQ1 0.8μM R08 exp435	0.055	View
LLY-283 2.6μM R06 exp290	0.053	View
UM0129480 7μM R02 exp85	0.052	View
Olaparib 4μM R08 exp512	0.052	View
iCRT14 30μM R08 exp492	0.052	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.052	View
CI-1040 9.5μM R08 exp472	0.119	View
Atovaquone 15μM R08 exp451	0.098	View
Aphidicolin 0.4μM R08 exp440	0.098	View
Deferoxamine 11μM R07 exp350	0.088	View
CR131-b 0.005μM R08 exp474	0.082	View
Etoposide 0.3μM R05 exp199	0.067	View
AICAR 240μM R05 exp211	0.063	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.06	View
AICAR 240μM R03 exp116	0.059	View
Doxorubicin 0.02μM R08 exp478	0.057	View
Etoposide 1μM R00 exp19	0.054	View
Actinomycin-D 0.001μM R00 exp3	0.053	View
Benzoate 20000μM R08 exp456	0.051	View

GO Term	Fold Change	Genes
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c	331.58	APAF1,CYCS,CASP9
mitochondrial RNA processing	110.53	HSD17B10,SUPV3L1,RPUSD4,PRORP
mitochondrial RNA metabolic process	89.96	HSD17B10,SUPV3L1,DARS2,YARS2,RPUSD4,TFAM,TEFM
mitochondrial nucleoid	65.79	HSD17B10,SUPV3L1,PRORP,TFAM,TEFM
nucleoid	65.79	HSD17B10,SUPV3L1,PRORP,TFAM,TEFM
mitochondrial gene expression	55.26	HSD17B10,SUPV3L1,MRPS18A,DARS2,MRPL23,MRPS14,YARS2,MRPL21,RPUSD4,PRORP,MRPL57,TFAM,TEFM,MRPS23
mitochondrial translation	40.94	MRPS18A,DARS2,MRPL23,MRPS14,YARS2,MRPL21,MRPL57,MRPS23
mitochondrial ribosome	37.68	MRPS18A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23
organellar ribosome	37.68	MRPS18A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23
structural constituent of ribosome	22.11	MRPS18A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23
mitochondrial protein-containing complex	20.17	HSD17B10,SUPV3L1,MRPS18A,COX5A,MRPL23,MRPS14,MRPL21,PRORP,MRPL57,MRPS23
ribosomal subunit	19.06	MRPS18A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23
mitochondrial matrix	17.49	HSD17B10,SUPV3L1,MRPS18A,DARS2,MRPL23,MRPS14,YARS2,TP53,MRPL21,RPUSD4,PRORP,MRPL57,TFAM,TEFM,MRPS23
translation	12.28	MRPS18A,DARS2,MRPL23,MRPS14,YARS2,MRPL21,MRPL57,MRPS23
mitochondrial inner membrane	12.07	HCCS,MRPS18A,CYCS,COX5A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23,TAMM41
peptide biosynthetic process	11.48	MRPS18A,DARS2,MRPL23,MRPS14,YARS2,MRPL21,MRPL57,MRPS23
organelle inner membrane	10.84	HCCS,MRPS18A,CYCS,COX5A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23,TAMM41
mitochondrial membrane	10.19	STARD7,HCCS,BAK1,MRPS18A,CYCS,COX5A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23,TAMM41,MARCHF5
mitochondrial envelope	9.57	STARD7,HCCS,BAK1,MRPS18A,CYCS,COX5A,MRPL23,MRPS14,MRPL21,MRPL57,MRPS23,TAMM41,MARCHF5

GSK-J4 1.5μM R08 exp441

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results