Centrinone 0.5μM R07 exp343

Inhibits PLK4, blocks centriole duplication, causes p53-dependent G1 arrest

Class / Subclass 1: Cell Cycle / Mitotic Inhibitor
Class / Subclass 2: Signal Transduction / Kinase Inhibitor

Compound References

PubChem Name: Centrinone
Synonyms: LCR-263
CAS #: 1798871-30-3
PubChem CID: 91801159
IUPAC: 2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine
INCHI Name: InChI=1S/C26H25F2N7O6S2/c1-15-12-21(33-32-15)29-24-23(40-2)25(34-8-10-41-11-9-34)31-26(30-24)42-20-7-6-17(13-18(20)27)43(38,39)14-16-4-3-5-19(22(16)28)35(36)37/h3-7,12-13H,8-11,14H2,1-2H3,(H2,29,30,31,32,33)
INCHI Key: HHJSKDRCUMVWKF-UHFFFAOYSA-N
Molecular Weight: 633.7
Canonical SMILES: CC1=CC(=NN1)NC2=C(C(=NC(=N2)SC3=C(C=C(C=C3)S(=O)(=O)CC4=C(C(=CC=C4)[N+](=O)[O-])F)F)N5CCOCC5)OC
Isomeric SMILES: N/A
Molecular Formula: C26H25F2N7O6S2

Compound Supplier

Supplier Name: Toronto Research Chemicals
Catalog #: C256613
Lot #: 3-TAH-188-1

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C26H25F2N7O6S2 634.13486; found 634.13738

Dose Response Curve

Platform ID: Centrinone
Min: -2.6996; Max: 75.3586

IC	Concentration (µM)
IC10	N/A
IC20	0.1695
IC30	0.3033
IC40	0.5164
IC50	0.9040
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 07
Dose: 500nM
Days of incubation: 8
Doublings: 1.0
Numbers of reads: 25730812

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
2/16	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
SLC5A3	-3.11	<0.01
DLGAP5	-2.87	0.02
QRICH1	-2.56	0.11
G6PD	-2.52	0.09
MGA	-2.50	0.09
OTUB1	-2.46	0.11
DYRK1A	-2.41	0.11
KIF18B	-2.39	0.11
KAT7	-2.38	0.11
DDX3X	-2.37	0.11
PPP3R1	-2.36	0.11
CEPT1	-2.30	0.11
PSMD4	-2.28	0.22
SART3	-2.26	0.51
RANBP1	-2.26	0.11
ANAPC15	-2.26	0.15
DKC1	-2.25	0.62
PDS5B	-2.25	0.11
SEPHS1	-2.25	0.11
TINF2	-2.24	0.16
ZNF44	-2.22	0.13
DOT1L	-2.22	0.17
ATP8B2	-2.20	0.27
CHMP7	-2.19	0.14
TCF4	-2.17	0.14
TOP1	-2.17	0.14
CLN3	-2.14	0.15
KIAA1432	-2.14	0.15
KPNB1	-2.14	0.66
MTCH2	-2.14	0.22
MTNR1B	2.19	0.09
TFDP1	2.20	0.13
APBA2	2.21	0.09
BUB1B	2.26	0.11
TRIM37	2.27	0.07
ITK	2.28	0.07
PPP2R3C	2.29	0.07
RBM14-RBM4	2.31	0.14
GCLC	2.32	0.06
RBM14	2.32	0.13
TUBE1	2.34	0.06
PLAA	2.35	0.06
CCDC41	2.36	0.08
PARP2	2.40	0.07
STK38	2.41	0.04
TUBD1	2.48	0.03
MARCH5	2.57	0.02
APAF1	2.57	0.02
DGKK	2.65	0.01
FAF2	2.87	0.01
ATMIN	2.90	<0.01
CDK2	2.93	<0.01
BAK1	3.21	<0.01
PGP	3.25	<0.01
TP53	3.39	<0.01
TRIP13	3.49	<0.01
ODC1	3.59	<0.01
MAD2L1	3.89	<0.01
BUB3	4.50	<0.01
MAD1L1	4.61	<0.01

Screen	Correlation	Plot
Cytochalasin-B 5μM R07 exp349	0.072	View
Latrunculin-B 10μM R07 exp374	0.071	View
GSK626616 14μM R08 exp485	0.069	View
Dorsomorphin 5μM R07 exp357	0.065	View
Tozasertib 0.1μM R07 exp414	0.063	View
Quercetin 20μM R08 exp517	0.063	View
RO-3307 4.7μM R02 exp80	0.062	View
GSK-J4 1-1.25μM to day4 R07 exp363	0.061	View
HMS-I1 10μM R06 exp256	0.059	View
Etoposide 1μM R00 exp19	0.058	View
Hippuristanol 0.12μM R08 exp488	0.058	View
Mitomycin-C 0.06μM R08 exp503	0.058	View
∆-9-Tetrahydrocannabinol 30μM R08 exp445	0.058	View
DABN racemic mixture R03 exp93	0.054	View
Doxorubicin 0.02μM R08 exp478	0.053	View
Etoposide 0.3μM R05 exp199	0.052	View
DABN 20μM R00 exp17	0.052	View
Nutlin-3A 1.6μM R06 exp294	0.052	View
Dinaciclib 0.007μM R07 exp355	0.051	View
BVD-523 15μM R02 exp67	0.062	View
5-Fluorouracil 20μM R00 exp2	0.055	View
Bisphenol A 100μM R06 exp269	0.051	View

GO Term	Fold Change	Genes
mitotic spindle checkpoint signaling	127.53	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
mitotic spindle assembly checkpoint signaling	127.53	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
spindle assembly checkpoint signaling	122.81	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
negative regulation of mitotic sister chromatid separation	114.34	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
negative regulation of mitotic sister chromatid segregation	110.53	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
negative regulation of chromosome segregation	106.96	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
negative regulation of metaphase/anaphase transition of cell cycle	106.96	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
negative regulation of chromosome separation	106.96	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
spindle checkpoint signaling	102.34	MAD1L1,BUB3,TRIP13,BUB1B,SPC25
negative regulation of sister chromatid segregation	95.28	MAD1L1,BUB3,TRIP13,BUB1B,SPC25
negative regulation of nuclear division	75.36	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
regulation of mitotic sister chromatid segregation	65.02	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
regulation of mitotic sister chromatid separation	59.21	MAD1L1,BUB3,MAD2L1,TRIP13,BUB1B,SPC25
mitotic cell cycle checkpoint signaling	36.84	MAD1L1,BUB3,MAD2L1,TRIP13,TP53,CDK2,BUB1B,SPC25
cell cycle checkpoint signaling	28.71	MAD1L1,BUB3,MAD2L1,TRIP13,TP53,CDK2,BUB1B,SPC25
negative regulation of mitotic cell cycle phase transition	27.81	MAD1L1,BUB3,MAD2L1,TRIP13,TP53,CDK2,BUB1B,SPC25
negative regulation of cell cycle process	21.26	MAD1L1,BUB3,MAD2L1,TRIP13,TP53,CDK2,RBM14,TRIM37,BUB1B,SPC25
negative regulation of organelle organization	18.88	MAD1L1,BUB3,MAD2L1,TRIP13,TP53,BAK1,RBM14,GCLC,TRIM37,BUB1B,SPC25
negative regulation of cell cycle	16.21	MAD1L1,BUB3,MAD2L1,TRIP13,TP53,CDK2,RBM14,TRIM37,BUB1B,SPC25

Centrinone 0.5μM R07 exp343

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results