CB-5083 0.4μM R08 exp468

CB-5083 0.4μM R08 exp468

Mechanism of Action

Inhibits p97 AAA-ATPase

Class / Subclass 1: Proteostasis / Unfoldase Inhibitor

Technical Notes

Protein References

PubChem Name: CB-5083
Synonyms: N/A
CAS #: 1542705-92-9
PubChem CID: 73051434
IUPAC: 1-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methylindole-4-carboxamide
INCHI Name: InChI=1S/C24H23N5O2/c1-15-12-18-17(22(25)30)8-5-9-21(18)29(15)24-27-20-10-11-31-14-19(20)23(28-24)26-13-16-6-3-2-4-7-16/h2-9,12H,10-11,13-14H2,1H3,(H2,25,30)(H,26,27,28)
INCHI Key: RDALZZCKQFLGJP-UHFFFAOYSA-N
Molecular Weight: 413.5
Canonical SMILES: CC1=CC2=C(C=CC=C2N1C3=NC4=C(COCC4)C(=N3)NCC5=CC=CC=C5)C(=O)N
Isomeric SMILES: N/A
Molecular Formula: C24H23N5O2

Protein Supplier

Supplier Name: Med Chem Express
Catalog #: HY-12861
Lot #: 19554

Protein Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C24H23N5O2 414.19245; found 414.1939

Dose Response Curve

Platform ID: CB5083
Min: -4.3018; Max: 99.5602

IC	Concentration (µM)
IC10	0.2207
IC20	0.3114
IC30	0.3915
IC40	0.4724
IC50	0.5612
IC60	0.6666
IC70	0.8043
IC80	1.0110
IC90	1.4270

Screen Summary

Round: 08
Dose: 400nM
Days of incubation: 8
Doublings: 2.5
Numbers of reads: 13284720

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
24/42	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
UBXN1	-4.71	<0.01
PLAA	-4.48	<0.01
ADK	-4.02	<0.01
DDI2	-3.76	<0.01
SRF	-3.74	<0.01
DERL1	-3.37	<0.01
NGLY1	-3.35	<0.01
NPRL2	-3.13	<0.01
BCL2L1	-3.10	<0.01
ZBTB10	-2.87	<0.01
DDX54	-2.82	0.02
CHMP2A	-2.74	0.06
NPLOC4	-2.73	0.03
MBTD1	-2.68	0.01
ASPSCR1	-2.57	0.02
NSFL1C	-2.55	0.02
RAD23B	-2.54	0.03
MTMR4	-2.53	0.02
SOX4	-2.51	0.07
CSK	-2.50	0.02
RANBP1	-2.49	0.02
CDK1	-2.48	0.07
SYS1	-2.45	0.08
CCL16	-2.42	0.06
DRD2	-2.42	0.03
NPRL3	-2.42	0.09
ZFAND5	-2.41	0.03
COG7	-2.40	0.03
DERL2	-2.35	0.07
ZNF296	-2.35	0.04
CCNL1	2.56	0.01
ROMO1	2.58	0.04
EBF1	2.67	0.03
FAM98B	2.67	0.01
USP14	2.70	<0.01
YLPM1	2.75	0.04
NUDT5	2.78	<0.01
RPTOR	2.83	<0.01
PCIF1	2.86	<0.01
DPH5	2.86	<0.01
THRAP3	2.87	<0.01
SLC7A1	2.89	0.03
UBR2	2.92	<0.01
THRA	2.92	<0.01
SCAP	3.00	<0.01
IKZF1	3.17	0.00
UBA6	3.22	0.00
DAZAP1	3.25	0.00
SRM	3.36	0.00
UBE2Z	3.37	0.00
ZBTB7A	3.39	0.00
RPS25	3.41	0.00
SLC39A10	3.43	0.00
EIF4A1	3.57	0.00
DPH6	3.64	0.00
CNBP	3.73	0.00
IKZF2	3.93	0.00
TPT1	4.13	0.00
TRIP12	4.80	0.00
IMPDH2	5.59	0.00

Screen	Correlation	Plot
Doxorubicin 0.02μM R08 exp478	0.084	View
Milciclib 2μM R08 exp502	0.083	View
Thimerosal 0.85μM R08 exp529	0.08	View
Hippuristanol 0.12μM R08 exp488	0.079	View
∆-9-Tetrahydrocannabinol 30μM R08 exp445	0.078	View
MLN-4924 0.2μM R00 exp21	0.075	View
PU-H71 1μM R08 exp515	0.074	View
Ethanol 0.01 R05 exp234	0.073	View
SNS-032 15μM R08 exp443	0.071	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.07	View
Sulforaphane 9μM R08 exp525	0.068	View
LLY-283 2.6μM R06 exp290	0.068	View
MS023 7μM R03 exp135	0.066	View
Staurosporine 0.02μM R08 exp524	0.066	View
Tubacin 1.6μM R07 exp416	0.062	View
GSK626616 14μM R08 exp485	0.061	View
LY2090314 0.003μM R08 exp500 no dilution day6	0.061	View
ML-792 0.2μM R08 exp505	0.06	View
Olaparib 4μM R08 exp512	0.06	View
Sulforaphane 9μM R08 exp526 no dilution day6	0.059	View
Cryptotanshinone 12μM R05 exp227	0.059	View
Cannabidiol 20μM R08 exp466	0.059	View
Nutlin-3A 1.6μM R06 exp294	0.058	View
Thapsigargin 0.005μM R07 exp407	0.058	View
CR131-b 0.005μM R08 exp474	0.057	View
LY2090314 0.003μM R08 exp499	0.055	View
RO-3307 4.7μM R02 exp80	0.055	View
Etoposide 0.3μM R05 exp199	0.055	View
Latrunculin-B 10μM R07 exp374	0.055	View
UM0129480 7μM R02 exp85	0.054	View
Radicicol 0.16μM R05 exp242	0.054	View
Dorsomorphin 5μM R07 exp357	0.053	View
JQ1 0.8μM R08 exp435	0.053	View
UM0125461 0.74μM R02 exp84	0.051	View
Deferoxamine 11μM R07 exp350	0.051	View
Bortezomib 0.005μM R00 exp6	0.076	View
Aphidicolin 0.4μM R08 exp440	0.071	View
Artemisinin 50μM R08 exp450	0.069	View
Bleomycin 5μM R08 exp459	0.061	View
BVD-523 15μM R02 exp67	0.058	View
Benzoate 20000μM R08 exp456	0.057	View
2-Deoxy-D-glucose 800μM R05 exp214	0.056	View
All-trans-Retinoic-Acid 40μM R07 exp334	0.055	View
Actinomycin-D 0.001μM R00 exp3	0.055	View
6-Thio-2-deoxyguanosine 2μM R06 exp259	0.053	View
Arsenate 40μM R06 exp264	0.052	View
AICAR 240μM R05 exp211	0.051	View

GO Term	Fold Change	Genes
GATOR1 complex	571.34	NPRL2,NPRL3
Hrd1p ubiquitin ligase ERAD-L complex	228.54	DERL1,DERL2
endoplasmic reticulum to cytosol transport	100.83	DERL1,NPLOC4,DERL2
retrograde protein transport, ER to cytosol	100.83	DERL1,NPLOC4,DERL2
protein exit from endoplasmic reticulum	63.48	DERL1,NPLOC4,DERL2
aorta morphogenesis	55.29	SRF,SOX4,NPRL3
ubiquitin binding	34.63	UBXN1,PLAA,DDI2,NPLOC4,NSFL1C,RAD23B
ubiquitin-like protein binding	29.05	UBXN1,PLAA,DDI2,NPLOC4,NSFL1C,RAD23B
ERAD pathway	23.56	DERL1,NGLY1,NPLOC4,DERL2
negative regulation of protein localization	14.00	BCL2L1,NSFL1C,CSK,DRD2,DERL2
proteasomal protein catabolic process	13.53	UBXN1,PLAA,DDI2,DERL1,NGLY1,NPLOC4,NSFL1C,RAD23B,DERL2
positive regulation of growth	11.85	PLAA,SRF,CDK1,DRD2,DERL2
proteasome-mediated ubiquitin-dependent protein catabolic process	11.59	UBXN1,PLAA,DERL1,NPLOC4,NSFL1C,RAD23B,DERL2
proteolysis involved in protein catabolic process	9.80	UBXN1,PLAA,DDI2,DERL1,NGLY1,CHMP2A,NPLOC4,NSFL1C,RAD23B,DERL2
ubiquitin-dependent protein catabolic process	8.94	UBXN1,PLAA,DERL1,CHMP2A,NPLOC4,NSFL1C,RAD23B,DERL2
modification-dependent protein catabolic process	8.77	UBXN1,PLAA,DERL1,CHMP2A,NPLOC4,NSFL1C,RAD23B,DERL2
modification-dependent macromolecule catabolic process	8.59	UBXN1,PLAA,DERL1,CHMP2A,NPLOC4,NSFL1C,RAD23B,DERL2
protein catabolic process	8.22	UBXN1,PLAA,DDI2,DERL1,NGLY1,CHMP2A,NPLOC4,NSFL1C,RAD23B,DERL2
macromolecule catabolic process	6.20	UBXN1,PLAA,DDI2,DERL1,NGLY1,CHMP2A,NPLOC4,NSFL1C,RAD23B,DERL2

Table of Contents

CB-5083 0.4μM R08 exp468

Mechanism of Action

Technical Notes

Protein References

Protein Supplier

Protein Characterization

Dose Response Curve

Screen Summary

Screen Results