ONC212 0.15μM R08 exp513

ONC212 0.15μM R08 exp513

Mechanism of Action

Inhibits mitochondrial CLPP protease, more potent derivative of TIC10/ONC201, possible agonist of GPR132

Class / Subclass 1: Proteostasis / Protease Inhibitor
Class / Subclass 2: Signal Transduction / GPCR Agonist

Technical Notes

Protein References

PubChem Name: 11-Benzyl-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one
Synonyms: N/A
CAS #: 1807861-48-8
PubChem CID: 124085867
IUPAC: 11-benzyl-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one
INCHI Name: InChI=1S/C24H23F3N4O/c25-24(26,27)19-8-6-18(7-9-19)15-31-22(32)20-16-29(14-17-4-2-1-3-5-17)12-10-21(20)30-13-11-28-23(30)31/h1-9H,10-16H2
INCHI Key: DFULPGUTXZTYKA-UHFFFAOYSA-N
Molecular Weight: 440.5
Canonical SMILES: C1CN(CC2=C1N3CCN=C3N(C2=O)CC4=CC=C(C=C4)C(F)(F)F)CC5=CC=CC=C5
Isomeric SMILES: N/A
Molecular Formula: C24H23F3N4O

Protein Supplier

Supplier Name: Med Chem Express
Catalog #: HY-111343
Lot #: 28375

Protein Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C24H23F3N4O 441.18967; found 441.19306

Dose Response Curve

Platform ID: ONC212
Min: 10.2172; Max: 89.4907

IC	Concentration (µM)
IC10	0.0002
IC20	0.0022
IC30	0.0111
IC40	0.0426
IC50	0.1460
IC60	0.5004
IC70	1.9150
IC80	9.8420
IC90	115.5000

Screen Summary

Round: 08
Dose: 150nM
Days of incubation: 8
Doublings: 0.7
Numbers of reads: 17653962

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
1/12	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
CDCA8	-3.05	0.20
EEFSEC	-2.97	0.02
SEL1L	-2.80	0.07
DHX8	-2.75	0.35
MDM2	-2.64	0.18
RNF32	-2.59	0.07
ACP1	-2.55	0.07
OTUB1	-2.53	0.16
ZNF783	-2.33	0.35
TINF2	-2.32	0.35
CDKL3	-2.29	0.33
CHMP2A	-2.27	0.48
GPX4	-2.22	0.26
ARHGEF35	-2.20	0.43
NCAPH	-2.18	0.44
POLR2E	-2.15	0.57
SURF6	-2.11	0.57
PDE3B	-2.09	0.35
PBRM1	-2.08	0.35
POLE	-2.08	0.63
CROCC	-2.07	0.50
NRCAM	-2.07	0.35
UBE2N	-2.06	0.35
ESPL1	-2.04	0.60
EBNA1BP2	-2.04	0.44
KPTN	-2.02	0.36
ZNF433	-2.02	0.36
BHMT2	-2.01	0.36
IRF5	-2.00	0.36
POLD2	-2.00	0.63
MRPS28	2.29	0.05
ANGEL2	2.30	0.05
RARS2	2.31	0.05
MAPKAP1	2.31	0.06
UQCR10	2.32	0.05
MRPS34	2.33	0.05
GEMIN7	2.33	0.05
MBTPS2	2.37	0.05
ALDH18A1	2.37	0.05
HSD17B10	2.37	0.05
ATF7IP	2.38	0.05
RIF1	2.39	0.05
SLC39A10	2.39	0.05
MRPS5	2.40	0.05
ACSL4	2.40	0.05
HEMGN	2.44	0.04
MRPL21	2.44	0.04
FASTKD5	2.49	0.05
KIAA0391	2.50	0.05
CEPT1	2.51	0.04
KIF2A	2.60	0.04
TP53	2.60	0.04
FASTKD1	2.61	0.04
MRPS6	2.72	0.04
STT3A	2.80	0.05
MRPS33	2.86	0.04
UHRF1	2.87	0.04
EARS2	3.34	<0.01
MIPEP	5.28	<0.01
CLPP	6.19	<0.01

Screen	Correlation	Plot
TIC10 10μM R08 exp532	0.145	View
Tanespimycin 14μM R08 exp527	0.095	View
Thimerosal 0.85μM R08 exp529	0.094	View
PU-H71 1μM R08 exp515	0.061	View
iCRT14 30μM R08 exp492	0.06	View
Vitamin-D3 40μM R08 exp536	0.051	View
GSK-J4 1.5μM R08 exp441	0.111	View
Atovaquone 15μM R08 exp451	0.076	View
Hydroxyurea 100μM R07 exp329	0.076	View
Amiloride 100μM R08 exp447	0.073	View
Ammonium tetrathiomolybdate 10μM R08 exp448	0.066	View
Mitomycin-C 0.06μM R08 exp503	0.063	View
Aphidicolin 0.4μM R08 exp440	0.06	View
CR131-b 0.005μM R08 exp474	0.06	View
Hinokiflavone 12μM R08 exp487	0.056	View
Artemisinin 50μM R08 exp450	0.055	View
CI-1040 9.5μM R08 exp472	0.051	View

GO Term	Fold Change	Genes
mitochondrial RNA processing	110.46	FASTKD1,PRORP,FASTKD5,HSD17B10
organellar small ribosomal subunit	89.08	MRPS33,MRPS6,MRPS5,MRPS34,MRPS28
mitochondrial small ribosomal subunit	71.26	MRPS6,MRPS5,MRPS34,MRPS28
mitochondrial RNA metabolic process	51.38	EARS2,FASTKD1,FASTKD5,HSD17B10
mitochondrial gene expression	47.68	EARS2,MRPS33,MRPS6,FASTKD1,PRORP,FASTKD5,MRPL21,MRPS5,HSD17B10,MRPS34,RARS2,MRPS28
mitochondrial translation	41.29	EARS2,MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,RARS2,MRPS28
organellar ribosome	37.66	MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,MRPS28
mitochondrial ribosome	37.66	MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,MRPS28
ribosomal subunit	19.15	MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,MRPS28
mitochondrial protein-containing complex	18.14	MRPS33,MRPS6,PRORP,MRPL21,MRPS5,HSD17B10,MRPS34,UQCR10,MRPS28
mitochondrial matrix	17.48	CLPP,MIPEP,EARS2,MRPS33,MRPS6,FASTKD1,TP53,PRORP,FASTKD5,MRPL21,MRPS5,HSD17B10,MRPS34,RARS2,MRPS28
ribosome	15.27	MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,MRPS28
translation	12.38	EARS2,MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,RARS2,MRPS28
peptide biosynthetic process	11.57	EARS2,MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,RARS2,MRPS28
peptide metabolic process	10.49	MIPEP,EARS2,MRPS33,MRPS6,MRPL21,MRPS5,MRPS34,RARS2,MRPS28
amide biosynthetic process	9.88	EARS2,MRPS33,MRPS6,MRPL21,ACSL4,MRPS5,MRPS34,RARS2,MRPS28
mitochondrial inner membrane	9.65	MRPS33,MRPS6,MRPL21,MRPS5,ALDH18A1,MRPS34,UQCR10,MRPS28
organelle inner membrane	8.66	MRPS33,MRPS6,MRPL21,MRPS5,ALDH18A1,MRPS34,UQCR10,MRPS28
amide metabolic process	8.03	MIPEP,EARS2,MRPS33,MRPS6,MRPL21,ACSL4,MRPS5,ALDH18A1,MRPS34,RARS2,MRPS28

Table of Contents

ONC212 0.15μM R08 exp513

Mechanism of Action

Technical Notes

Protein References

Protein Supplier

Protein Characterization

Dose Response Curve

Screen Summary

Screen Results