GSK626616 14μM R08 exp485

GSK626616 14μM R08 exp485

Mechanism of Action

Inhibits DYRK3, prevents stress granule dissolution, mTORC1 release

Class / Subclass 1: Signal Transduction / Kinase Inhibitor

Technical Notes

Protein References

PubChem Name: 4(5H)-Thiazolone, 2-((2,6-dichlorophenyl)amino)-5-(6-quinoxalinylmethylene)-, (5Z)-
Synonyms: N/A
CAS #: 1025821-33-3
PubChem CID: 135416229
IUPAC: (5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one
INCHI Name: InChI=1S/C18H10Cl2N4OS/c19-11-2-1-3-12(20)16(11)23-18-24-17(25)15(26-18)9-10-4-5-13-14(8-10)22-7-6-21-13/h1-9H,(H,23,24,25)/b15-9-
INCHI Key: RJPNRXFBYZVRIB-DHDCSXOGSA-N
Molecular Weight: 401.3
Canonical SMILES: C1=CC(=C(C(=C1)Cl)N=C2NC(=O)C(=CC3=CC4=NC=CN=C4C=C3)S2)Cl
Isomeric SMILES: C1=CC(=C(C(=C1)Cl)N=C2NC(=O)/C(=C/C3=CC4=NC=CN=C4C=C3)/S2)Cl
Molecular Formula: C18H10Cl2N4OS

Protein Supplier

Supplier Name: Tocris Bioscience
Catalog #: 6638
Lot #: 1A/216989

Protein Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C18H10Cl2N4OS 401.00251; found 401.00255

Dose Response Curve

Platform ID: GSK626616
Min: -3.2829; Max: 99.0208

IC	Concentration (µM)
IC10	8.4010
IC20	11.1700
IC30	13.4900
IC40	15.7500
IC50	18.1600
IC60	20.9400
IC70	24.4500
IC80	29.5400
IC90	39.2700

Screen Summary

Round: 08
Dose: 14µM
Days of incubation: 8
Doublings: 1.9
Numbers of reads: 16240671

Screen Results

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
22/93	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
CLK3	-5.35	<0.01
TCF4	-3.48	<0.01
STMN1	-3.38	<0.01
BRD1	-3.10	<0.01
NRAS	-2.98	<0.01
QRICH1	-2.93	<0.01
PDS5B	-2.87	<0.01
SEPHS1	-2.87	<0.01
ZBTB10	-2.79	<0.01
FTO	-2.77	<0.01
SNRPD1	-2.74	0.07
OTUB1	-2.74	0.02
GAK	-2.73	<0.01
STYX	-2.70	0.02
KIF18A	-2.65	0.01
SRPK1	-2.58	0.02
CLK1	-2.53	0.02
KAT7	-2.51	0.02
C9orf41	-2.51	0.07
TRIM44	-2.50	0.04
DCAF15	-2.49	0.04
RNF4	-2.48	0.04
XPO6	-2.35	0.04
SKA1	-2.34	0.04
FZR1	-2.32	0.08
C1orf21	-2.29	0.06
RBM12	-2.28	0.06
NSMCE1	-2.26	0.06
WAPAL	-2.26	0.10
SHOC2	-2.24	0.10
IKZF2	3.46	0.00
PCIF1	3.48	0.00
RMND5A	3.49	0.00
PLAA	3.62	0.00
TSC2	3.62	0.00
ELF2	3.69	0.00
RPL5	3.69	0.00
CDK2	3.79	0.00
APAF1	3.81	0.00
GPATCH8	3.84	0.00
UBQLN1	4.00	0.00
GID8	4.19	0.00
SMEK1	4.35	0.00
MAEA	4.38	0.00
VDAC2	4.39	0.00
FAM58A	4.40	0.00
EIF2AK4	4.53	0.00
DEPDC5	4.56	0.00
HEATR3	4.61	0.00
RPL22	4.67	0.00
RBM26	4.75	0.00
NPRL2	4.82	0.00
MARCH5	5.05	0.00
YLPM1	5.53	0.00
NPRL3	5.56	0.00
RPL11	5.91	0.00
BAK1	5.93	0.00
DDX3X	6.48	0.00
EIF4A1	7.54	0.00
TP53	7.60	0.00

Screen	Correlation	Plot
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.104	View
Staurosporine 0.02μM R08 exp524	0.101	View
Hippuristanol 0.12μM R08 exp488	0.096	View
Olaparib 4μM R08 exp512	0.092	View
MS023 2μM R03 exp134	0.092	View
RO-3307 4.7μM R02 exp80	0.089	View
Mitomycin-C 0.06μM R08 exp503	0.087	View
MK2206 4μM R08 exp504	0.084	View
Thapsigargin 0.005μM R07 exp407	0.082	View
Thimerosal 0.85μM R08 exp529	0.08	View
Quercetin 20μM R08 exp517	0.073	View
Lead acetate 2000μM R08 exp498 no dilution day6	0.07	View
UM0129480 7μM R02 exp85	0.069	View
Pimelic-diphenylamide-106 5μM R00 exp28	0.068	View
Latrunculin-B 10μM R07 exp374	0.068	View
Milciclib 2μM R08 exp502	0.068	View
Lead acetate 2000μM R08 exp497	0.067	View
ML-792 0.2μM R08 exp505	0.066	View
MS023 7μM R03 exp135	0.064	View
I-BRD9 4μM R07 exp365	0.063	View
Tozasertib 0.1μM R07 exp414	0.062	View
THZ1 0.06μM R08 exp531	0.061	View
Wortmannin 5μM R00 exp38	0.061	View
Nutlin-3A 1.6μM R06 exp294	0.061	View
Sulforaphane 9μM R08 exp525	0.061	View
TRAIL 5ng/ml R00 exp35	0.06	View
SNS-032 15μM R08 exp443	0.058	View
JQ1 0.8μM R08 exp435	0.055	View
MLN-4924 0.2μM R00 exp21	0.055	View
Tubacin 1.6μM R07 exp416	0.055	View
Rapamycin 10μM R00 exp30	0.054	View
Rapamycin 2μM R07 exp306	0.054	View
LB-100 2μM R05 exp210	0.052	View
Tanespimycin 14μM R08 exp527	0.051	View
Actinomycin-D 0.001μM R00 exp3	0.12	View
AICAR 240μM R03 exp116	0.118	View
Benzoate 20000μM R08 exp456	0.101	View
Dorsomorphin 5μM R07 exp357	0.089	View
5-Fluorouracil 20μM R00 exp2	0.087	View
AICAR 240μM R05 exp211	0.087	View
CR131-b 0.005μM R08 exp474	0.08	View
Etoposide 0.3μM R05 exp199	0.079	View
Aphidicolin 0.4μM R08 exp440	0.079	View
Dexamethasone 0.006 to 0.015μM on day4 R07 exp352	0.075	View
Centrinone 0.5μM R07 exp343	0.069	View
Dinaciclib 0.007μM R07 exp355	0.067	View
Ethanol 0.01 R05 exp234	0.065	View
Bleomycin 5μM R08 exp459	0.064	View
Arsenate 40μM R06 exp264	0.063	View
Erlotinib 10μM R05 exp216	0.062	View
Doxorubicin 0.02μM R08 exp478	0.062	View
CB-5083 0.4μM R08 exp468	0.061	View
Cytochalasin-B 5μM R07 exp349	0.061	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.056	View
BML-284 0.09μM R08 exp460	0.056	View
Etoposide 0.1μM R05 exp198	0.055	View
Demecolcine 0.03μM R05 exp228	0.055	View
Azithromycin 100μM R08 exp452	0.054	View
CI-1040 9.5μM R08 exp472	0.053	View
Etoposide 1μM R00 exp19	0.051	View
BI-D1870 3.15μM R02 exp66	0.051	View
Combretastatin A4 0.002 to 0.003μM day4 R04 exp179	0.051	View
CAY10603 0.55μM R08 exp467	0.051	View
GSK-J4 1-1.25μM to day4 R07 exp363	0.051	View

GO Term	Fold Change	Genes
chromosomal region	11.52	PDS5B,ZBTB10,KIF18A,KAT7,SKA1,NSMCE1,WAPL

GO Term	Fold Change	Genes
GATOR1 complex	552.30	NPRL3,NPRL2
negative regulation of protein neddylation	368.20	RPL11,RPL5
Seh1-associated complex	236.70	NPRL3,NPRL2,DEPDC5
negative regulation of TORC1 signaling	53.88	NPRL3,NPRL2,DEPDC5,TSC2
cellular response to amino acid starvation	46.02	NPRL3,NPRL2,DEPDC5,EIF2AK4
response to amino acid starvation	43.32	NPRL3,NPRL2,DEPDC5,EIF2AK4
negative regulation of TOR signaling	33.47	NPRL3,NPRL2,DEPDC5,TSC2
regulation of TORC1 signaling	25.69	NPRL3,NPRL2,DEPDC5,TSC2
cellular response to starvation	19.38	TP53,NPRL3,NPRL2,DEPDC5,EIF2AK4,TSC2
regulation of intrinsic apoptotic signaling pathway	15.96	TP53,DDX3X,RPL11,VDAC2,UBQLN1
response to starvation	15.78	TP53,NPRL3,NPRL2,DEPDC5,EIF2AK4,TSC2
response to endoplasmic reticulum stress	14.73	TP53,DDX3X,BAK1,EIF2AK4,UBQLN1,APAF1
cellular response to nutrient levels	14.22	TP53,NPRL3,NPRL2,DEPDC5,EIF2AK4,TSC2
cellular response to extracellular stimulus	12.65	TP53,NPRL3,NPRL2,DEPDC5,EIF2AK4,TSC2
cellular response to external stimulus	11.82	TP53,BAK1,NPRL3,NPRL2,DEPDC5,EIF2AK4,TSC2
regulation of apoptotic signaling pathway	10.34	TP53,DDX3X,BAK1,RPL11,VDAC2,UBQLN1,APAF1
enzyme activator activity	7.79	DDX3X,NPRL3,NPRL2,DEPDC5,PPP4R3A,APAF1,TSC2,PLAA
regulation of proteolysis	7.49	TP53,DDX3X,BAK1,RPL11,UBQLN1,APAF1,CDK2,RPL5
negative regulation of protein metabolic process	5.88	TP53,DDX3X,BAK1,RPL11,EIF2AK4,RPL5,TSC2,PLAA,PCIF1

Table of Contents

GSK626616 14μM R08 exp485

Mechanism of Action

Technical Notes

Protein References

Protein Supplier

Protein Characterization

Dose Response Curve

Screen Summary

Screen Results