NMS-873 0.07μM R07 exp380

NMS-873 0.07μM R07 exp380

Mechanism of Action

Inhibits p97 AAA-ATPase

Class / Subclass 1: Proteostasis / Ubiquitin-Proteasome Inhibitor

Technical Notes

Protein References

PubChem Name: CID 71521142
Synonyms: N/A
CAS #: 1418013-75-8
PubChem CID: 71521142
IUPAC: 3-[3-cyclopentylsulfanyl-5-[[3-methyl-4-(4-methylsulfonylphenyl)phenoxy]methyl]-1,2,4-triazol-4-yl]pyridine
INCHI Name: InChI=1S/C27H28N4O3S2/c1-19-16-22(11-14-25(19)20-9-12-24(13-10-20)36(2,32)33)34-18-26-29-30-27(35-23-7-3-4-8-23)31(26)21-6-5-15-28-17-21/h5-6,9-17,23H,3-4,7-8,18H2,1-2H3
INCHI Key: UJGTUKMAJVCBIS-UHFFFAOYSA-N
Molecular Weight: 520.7
Canonical SMILES: CC1=C(C=CC(=C1)OCC2=NN=C(N2C3=CN=CC=C3)SC4CCCC4)C5=CC=C(C=C5)S(=O)(=O)C
Isomeric SMILES: N/A
Molecular Formula: C27H28N4O3S2

Protein Supplier

Supplier Name: Ark Pharm Inc.
Catalog #: AK175592
Lot #: WG0305592-170215001

Protein Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C27H28N4O3S2 521.16756; found 521.16873

Dose Response Curve

Platform ID: NMS-873
Min: 2.2487; Max: 99.2142

IC	Concentration (µM)
IC10	N/A
IC20	0.0307
IC30	0.0729
IC40	0.1455
IC50	0.2720
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 07
Dose: 70nM
Days of incubation: 8
Doublings: 4.2
Numbers of reads: 19956950

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
1/5	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
GOT1	-5.76	<0.01
ALDOA	-3.13	0.30
RSRC2	-2.59	0.46
SUCLG1	-2.57	0.30
VPS25	-2.47	0.44
SUCLA2	-2.40	0.30
MSL1	-2.39	0.30
GMPPB	-2.35	0.44
APOBEC3F	-2.33	0.30
CNOT8	-2.28	0.30
ENO1	-2.27	0.30
NCLN	-2.21	0.33
PTEN	-2.18	0.30
INTS3	-2.18	0.44
KIDINS220	-2.17	0.30
GPI	-2.15	0.50
LIPT1	-2.13	0.30
HK1	-2.11	0.31
GIGYF2	-2.10	0.47
SOD2	-2.06	0.44
TRADD	-2.05	0.44
AHCYL1	-2.05	0.44
WDR20	-2.02	0.44
MED20	-2.00	0.44
CCDC101	-2.00	0.44
CLEC4C	-1.98	0.44
GCDH	-1.96	0.44
CXorf51A	-1.95	0.44
YRDC	-1.95	0.47
CXorf51B	-1.94	0.44
WARS2	2.09	0.24
NDUFA1	2.11	0.24
CTU1	2.12	0.19
MTG1	2.12	0.24
KLF16	2.12	0.30
CLK1	2.13	0.19
PANX3	2.18	0.24
ATP5A1	2.19	0.14
ZNF343	2.24	0.19
WDR83	2.24	0.13
FAM98B	2.26	0.13
FOXA3	2.29	0.13
GFM2	2.29	0.13
BRMS1	2.31	0.24
MRPS35	2.35	0.23
MIR205HG	2.39	0.57
SHMT2	2.40	0.13
PTMA	2.41	0.13
HSCB	2.42	0.08
SIN3A	2.47	0.24
RPS3A	2.48	0.14
PDS5B	2.60	0.05
RPL11	2.60	0.24
ATP5B	2.70	0.03
ATP5L	2.73	0.08
ITPK1	2.79	0.02
ATP5D	2.83	0.07
CCND3	2.96	0.13
ACSL3	3.18	<0.01
SLC25A51	4.12	<0.01

Screen	Correlation	Plot
QNZ 0.01μM R05 exp241	0.107	View
Rotenone 0.07μM R08 exp431	0.104	View
Phenformin 20μM R05 exp212	0.091	View
QNZ 0.01μM R08 exp439	0.088	View
Phenformin 20μM R03 exp143	0.051	View
Mubritinib 0.2μM R01 exp48	0.076	View
Mubritinib 0.2μM R02 exp65	0.059	View
Chloramphenicol 20μM R00 exp13	0.052	View

GO Term	Fold Change	Genes
succinate-CoA ligase activity	637.65	SUCLG1,SUCLA2
glycolytic process	60.73	ALDOA,ENO1,GPI,HK1
pyruvate metabolic process	38.07	ALDOA,ENO1,GPI,HK1
carbohydrate catabolic process	23.62	ALDOA,ENO1,GPI,HK1
glucose metabolic process	21.80	GOT1,ENO1,GPI,HK1
hexose metabolic process	20.31	GOT1,ALDOA,ENO1,GPI,HK1
monosaccharide metabolic process	17.14	GOT1,ALDOA,ENO1,GPI,HK1
generation of precursor metabolites and energy	11.87	ALDOA,SUCLG1,SUCLA2,ENO1,GPI,HK1,SOD2
oxoacid metabolic process	6.15	GOT1,ALDOA,SUCLA2,ENO1,GPI,LIPT1,HK1,GCDH
organic acid metabolic process	6.09	GOT1,ALDOA,SUCLA2,ENO1,GPI,LIPT1,HK1,GCDH

GO Term	Fold Change	Genes
proton-transporting ATP synthase activity, rotational mechanism	157.90	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A
mitochondrial proton-transporting ATP synthase complex	147.37	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A
proton-transporting ATP synthase complex	138.16	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A
proton channel activity	100.48	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A
proton motive force-driven mitochondrial ATP synthesis	52.14	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
proton motive force-driven ATP synthesis	46.05	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
ATP biosynthetic process	39.47	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
purine ribonucleoside triphosphate biosynthetic process	34.11	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
purine nucleoside triphosphate biosynthetic process	33.70	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
oxidative phosphorylation	33.49	SLC25A51,ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
ribonucleoside triphosphate biosynthetic process	32.13	ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
aerobic respiration	23.52	SLC25A51,ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
ligase activity	20.72	ACSL3,ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,WARS2
cellular respiration	19.62	SLC25A51,ATP5F1D,ATP5MG,ATP5F1B,ATP5F1A,NDUFA1
purine-containing compound biosynthetic process	17.50	ACSL3,ATP5F1D,ATP5MG,ATP5F1B,SHMT2,ATP5F1A,NDUFA1
mitochondrial inner membrane	10.84	SLC25A51,ATP5F1D,ATP5MG,ATP5F1B,SHMT2,MRPS35,ATP5F1A,MTG1,NDUFA1
organelle inner membrane	9.73	SLC25A51,ATP5F1D,ATP5MG,ATP5F1B,SHMT2,MRPS35,ATP5F1A,MTG1,NDUFA1
mitochondrial membrane	7.83	SLC25A51,ACSL3,ATP5F1D,ATP5MG,ATP5F1B,SHMT2,MRPS35,ATP5F1A,MTG1,NDUFA1
mitochondrial envelope	7.35	SLC25A51,ACSL3,ATP5F1D,ATP5MG,ATP5F1B,SHMT2,MRPS35,ATP5F1A,MTG1,NDUFA1

Table of Contents

NMS-873 0.07μM R07 exp380

Mechanism of Action

Technical Notes

Protein References

Protein Supplier

Protein Characterization

Dose Response Curve

Screen Summary

Screen Results