Tozasertib 0.1μM R07 exp414

Inhibits Aurora A,B,C kinases, blocks cytokinesis, also inhibits RIPK1 and blocks necroptosis

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

Compound References

PubChem Name: Tozasertib
Synonyms: VX 680; MK-0457
CAS #: 639089-54-6
PubChem CID: 5494449
IUPAC: N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide
INCHI Name: InChI=1S/C23H28N8OS/c1-15-13-20(29-28-15)25-19-14-21(31-11-9-30(2)10-12-31)27-23(26-19)33-18-7-5-17(6-8-18)24-22(32)16-3-4-16/h5-8,13-14,16H,3-4,9-12H2,1-2H3,(H,24,32)(H2,25,26,27,28,29)
INCHI Key: GCIKSSRWRFVXBI-UHFFFAOYSA-N
Molecular Weight: 464.6
Canonical SMILES: CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C
Isomeric SMILES: N/A
Molecular Formula: C23H28N8OS

Compound Supplier

Supplier Name: Toronto Research Chemicals
Catalog #: T700000
Lot #: 14-GHZ-9-1

Compound Characterization

HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C23H28N8OS 465.21795; found 465.21974

Dose Response Curve

Platform ID: Tosazertib
Min: -23.2513; Max: 58.2889

IC	Concentration (µM)
IC10	N/A
IC20	2.9341
IC30	3.8568
IC40	5.3417
IC50	2.7487
IC60	N/A
IC70	N/A
IC80	N/A
IC90	N/A

Screen Summary

Round: 07
Dose: 100nM
Days of incubation: 8
Doublings: -0.1
Numbers of reads: 17969844

Sensitive/Resistant hits (FDR<0.05)	CRANKS	Score Plot	Top 30 Genes	Screen Similarity	Top 30 Sensitive GO terms	Top 30 Resistant GO terms
0/75	Scores	View	View	View	View	View

Gene	CRANKS Score	FDR
UPF2	-2.69	0.41
MGA	-2.46	0.41
CCDC147	-2.40	0.41
KEAP1	-2.28	0.41
PSMD11	-2.28	0.41
PRPF18	-2.27	0.41
TFPT	-2.25	0.41
LRR1	-2.24	0.51
TCOF1	-2.24	0.41
PPP2R2A	-2.23	0.41
TLR7	-2.14	0.41
TMSB15B	-2.12	0.66
MFI2	-2.12	0.41
SAMM50	-2.12	0.41
TRIM46	-2.09	0.41
MCM5	-2.06	0.65
CCDC24	-2.06	0.51
GPR137	-2.05	0.41
ERGIC2	-2.04	0.41
RPL13	-2.04	0.71
WDR45	-2.04	0.41
PSMD13	-2.04	0.51
NELFA	-2.03	0.45
PPP2R1A	-2.03	0.41
ZNF407	-2.02	0.41
NUTF2	-2.02	0.71
PHACTR3	-2.01	0.52
IAPP	-1.99	0.41
PUS7	-1.98	0.51
DDX3Y	-1.97	0.41
CEP78	3.62	0.00
CEP152	3.64	0.00
KIAA0586	3.71	0.00
WBP11	3.72	0.00
TUBD1	4.06	0.00
CEP44	4.15	0.00
BUB3	4.17	0.00
HYLS1	4.40	0.00
EIF4A1	4.63	0.00
FOPNL	4.63	0.00
TUBE1	4.71	0.00
TP53	4.91	0.00
RTTN	5.19	0.00
SCLT1	5.31	0.00
C16orf59	5.65	0.00
NIN	5.81	0.00
CEP76	5.94	0.00
CEP128	6.02	0.00
CASP2	6.27	0.00
C14orf80	6.42	0.00
ODF2	6.48	0.00
ANKRD26	6.62	0.00
PIDD	6.68	0.00
CEP120	6.68	0.00
CRADD	6.90	0.00
OFD1	6.93	0.00
CCDC41	7.41	0.00
PIBF1	7.55	0.00
KIAA0753	7.75	0.00
C2CD3	7.94	0.00

Screen	Correlation	Plot
Latrunculin-B 10μM R07 exp374	0.251	View
Cytochalasin-B 5μM R07 exp349	0.223	View
RO-3307 4.7μM R02 exp80	0.132	View
Hippuristanol 0.12μM R08 exp489 no dilution day6	0.064	View
Centrinone 0.5μM R07 exp343	0.063	View
GSK626616 14μM R08 exp485	0.062	View
Hippuristanol 0.12μM R08 exp488	0.056	View
Tanespimycin 14μM R08 exp527	0.056	View
Etoposide 0.3μM R05 exp199	0.055	View
Genistein 15μM R07 exp360	0.054	View
Doxorubicin 0.02μM R08 exp478	0.052	View
AICAR 240μM R05 exp211	0.051	View

GO Term	Fold Change	Genes
centriole-centriole cohesion	184.21	ODF2,NIN,RTTN,CEP44
centriole replication	138.16	C2CD3,KIAA0753,OFD1,RTTN,CEP44,CEP152
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	130.03	CRADD,PIDD1,CASP2,TP53
centriole assembly	106.96	C2CD3,KIAA0753,OFD1,RTTN,CEP44,CEP152
centrosome duplication	94.74	C2CD3,KIAA0753,OFD1,RTTN,CEP44,CEP152
centriole	67.67	C2CD3,KIAA0753,CEP83,OFD1,CEP120,ODF2,CEP128,CEP76,NIN,SCLT1,RTTN,CEP20,HYLS1,CEP44,TUBD1,KIAA0586,CEP152,CEP78
centrosome cycle	61.40	C2CD3,KIAA0753,OFD1,CEP120,ODF2,NIN,RTTN,TUBE1,CEP44,CEP152
microtubule organizing center organization	51.65	C2CD3,KIAA0753,OFD1,CEP120,ODF2,NIN,RTTN,TUBE1,CEP44,CEP152
cilium organization	20.53	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,ODF2,SCLT1,RTTN,CEP20,HYLS1,KIAA0586,CEP78
centrosome	18.90	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,CEP120,ANKRD26,ODF2,CEP128,CEP76,NIN,SCLT1,RTTN,TP53,TUBE1,CEP20,HYLS1,CEP44,KIAA0586,CEP152,CEP78
cilium assembly	16.86	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,SCLT1,CEP20,HYLS1,KIAA0586
microtubule organizing center	15.10	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,CEP120,ANKRD26,ODF2,CEP128,CEP76,NIN,SCLT1,RTTN,TP53,TUBE1,CEP20,HYLS1,CEP44,TUBD1,KIAA0586,CEP152,CEP78
microtubule cytoskeleton organization	13.35	C2CD3,KIAA0753,PIBF1,OFD1,CEP120,ODF2,NIN,RTTN,TUBE1,CEP20,CEP44,TUBD1,CEP152
plasma membrane bounded cell projection assembly	12.59	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,SCLT1,CEP20,HYLS1,KIAA0586
cell projection assembly	12.22	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,SCLT1,CEP20,HYLS1,KIAA0586
cilium	10.58	C2CD3,CEP83,OFD1,ODF2,CEP128,NIN,SCLT1,RTTN,CEP20,HYLS1,TUBD1,KIAA0586,CEP78
cell cycle process	10.14	C2CD3,KIAA0753,PIBF1,OFD1,CRADD,CEP120,PIDD1,ODF2,CASP2,NIN,RTTN,TP53,TUBE1,BUB3,CEP44,CEP152
microtubule-based process	9.22	C2CD3,KIAA0753,PIBF1,OFD1,CEP120,ODF2,NIN,RTTN,TUBE1,CEP20,CEP44,TUBD1,CEP152
organelle assembly	8.37	C2CD3,KIAA0753,PIBF1,CEP83,OFD1,SCLT1,RTTN,CEP20,HYLS1,CEP44,KIAA0586,CEP152

Tozasertib 0.1μM R07 exp414

Mechanism of Action

Technical Notes

Compound References

Compound Supplier

Compound Characterization

Dose Response Curve

Screen Summary

Screen Results