Compound Detail

CHEMBL572878

TOZASERTIB

🧪 Phase II

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🧪 Phase II

Cc1cc(Nc2cc(N3CCN(C)CC3)nc(Sc3ccc(NC(=O)C4CC4)cc3)n2)n[nH]1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL572878
Name	TOZASERTIB
Phase	Phase II
Structure Type	MOL
InChI Key	GCIKSSRWRFVXBI-UHFFFAOYSA-N

Known Names

MK-0457 Tozasertib VX-680

514

Targets

1,080

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

464.6

MW (Da)

3.50

ALogP

HBA

HBD

102.1

PSA (Å²)

0.46

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

USAN Stem	-sertib
USAN Year	2008

Extended Properties

Molecular Formula	C23H28N8OS
MW	464.60
Aromatic Rings	3
Heavy Atoms	33
NP-Likeness	-2.01

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serine/threonine-protein kinase Aurora inhibitor	INHIBITOR	Serine/threonine-protein kinase Aurora	✓	✓

Indications

Carcinoma, Non-Small-Cell Lung Leukemia Colorectal Neoplasms Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Myelodysplastic Syndromes Neoplasms Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma

Activity Summary

IC50 519 meas. best 9.62

Kd 431 meas. best 9.48

Ki 127 meas. best 9.43

EC50 3 meas. best 6.92

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Aurora kinase A CHEMBL4722	IC50	9.62	8.2913	0.2	31
Aurora kinase A CHEMBL4722	Kd	9.48	8.7018	0.3	11
Aurora kinase A CHEMBL4722	Ki	9.43	9.1139	0.4	18
Small ribosomal subunit protein mS38 CHEMBL5910	Ki	9.22	9.22	0.6	1
Aurora kinase B CHEMBL2185	Ki	8.74	7.9994	1.8	17
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	8.52	7.6165	3.0	23
High affinity nerve growth factor receptor CHEMBL2815	Kd	8.5	7.69	3.2	4
BE-13 CHEMBL2366303	IC50	8.47	8.47	3.4	1
Tyrosine-protein kinase ABL2 CHEMBL4014	Kd	8.4	7.915	4.0	4
RS4-11 CHEMBL2366159	IC50	8.39	8.39	4.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	8.37	7.7159	4.3	17
Aurora kinase C CHEMBL3935	IC50	8.34	8.104	4.6	5
Aurora kinase C CHEMBL3935	Ki	8.34	8.34	4.6	14
Aurora kinase C CHEMBL3935	Kd	8.22	8.2067	6.0	3
Serine/threonine-protein kinase TBK1 CHEMBL5408	IC50	8.21	8.21	6.2	1
Aurora kinase B CHEMBL2185	Kd	8.15	7.845	7.0	4
Serine/threonine-protein kinase PLK4 CHEMBL3788	Ki	8.12	7.9767	7.7	6
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Kd	8.07	7.5175	8.6	8
Serine/threonine-protein kinase PLK4 CHEMBL3788	Kd	8.05	7.605	9.0	4
MFH-ino CHEMBL2366262	IC50	8.01	8.01	9.9	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Ki	7.9	7.9	12.6	1
NTERA-2-cl-D1 CHEMBL614206	IC50	7.84	7.84	14.3	1
Aurora kinase B CHEMBL2185	IC50	7.83	7.4462	14.7	26
Myosin light chain kinase, smooth muscle CHEMBL3062	Kd	7.82	7.82	15.0	1
Myosin light chain kinase CHEMBL4627	Kd	7.82	7.82	15.0	2
Tyrosine-protein kinase ABL1 CHEMBL1862	Ki	7.8	7.5667	15.8	3
Discoidin domain-containing receptor 2 CHEMBL5122	IC50	7.75	7.185	18.0	2
Aurora kinase B-A CHEMBL2176838	IC50	7.72	7.72	19.0	1
COLO 205 CHEMBL614561	IC50	7.72	7.72	19.0	1
Receptor-interacting serine/threonine-protein kinase 1 CHEMBL5464	Kd	7.7	7.7	20.0	3
NON-PROTEIN TARGET CHEMBL3879801	IC50	7.67	5.984	21.2	5
HCT-116 CHEMBL394	IC50	7.62	6.48	24.0	11
697 CHEMBL2366253	IC50	7.61	7.61	24.7	1
NALM-6 CHEMBL614187	IC50	7.59	7.59	25.5	1
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	Kd	7.55	7.55	28.0	2
Ephrin type-B receptor 6 CHEMBL5836	Kd	7.55	7.55	28.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	7.52	7.52	30.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Ki	7.52	7.36	30.0	7
Bcr/Abl fusion protein CHEMBL2096618	Ki	7.52	7.45	30.0	2
Tyrosine-protein kinase Blk CHEMBL2250	Ki	7.5	7.5	31.6	1
Protein delta homolog 1 CHEMBL5671	Ki	7.45	7.45	35.8	2
U-937 CHEMBL612794	IC50	7.44	7.44	36.0	2
HL-60 CHEMBL383	IC50	7.42	6.3733	38.2	3
Maternal embryonic leucine zipper kinase CHEMBL4578	Ki	7.4	7.4	39.8	1
Myosin light chain kinase 2, skeletal/cardiac muscle CHEMBL2777	Kd	7.37	7.37	43.0	2
ES8 CHEMBL2366069	IC50	7.34	7.34	46.1	1
MCF7 CHEMBL387	IC50	7.32	5.81	48.0	7
Cyclin-dependent kinase-like 2 CHEMBL5728	Kd	7.31	7.31	49.0	1
Bcr/Abl fusion protein CHEMBL2096618	IC50	7.3	7.3	50.1	1
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	7.29	7.29	51.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
Cmax	650.0	nM	Homo sapiens
T1/2	15.0	hr	Homo sapiens
T1/2	0.4167	hr	Homo sapiens
T1/2	15.0	hr	Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Aurora kinase A	IC50	=	0.24	nM	9.62	Inhibition of Aurora A by 33P minase hotspot assay	22803810
Aurora kinase A	Kd	=	0.3333	nM	9.48	Multi-Cycle Kinetic parameter establishment of 8 compounds to gain n=3Completed ...	-
Aurora kinase A	Ki	=	0.37	nM	9.43	Inhibition of Aurora A (unknown origin)	31862411
Aurora kinase A	Kd	=	0.5012	nM	9.3	Binding affinity to DNA-tagged human partial length AURKA expressed in mammalian...	29746776
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of Aurora A kinase	18243698
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of Aurora A	20420387
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of aurora A	20573509
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of aurora A (unknown origin)	23664099
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of N-terminal His-6-tagged recombinant Aurora 1 (62 to 344) (unknown ...	24681066
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of recombinant N-terminal His6-tagged Aurora A (62 to 344 residues) (...	30502115
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of Aurora-A by coupled assay	19447622
Aurora kinase A	Ki	=	0.6	nM	9.22	In vitro inhibition constant for Aurora-A	16451062
Small ribosomal subunit protein mS38	Ki	=	0.6	nM	9.22	Inhibition of Aurora A	18077425
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of aurora A kinase	19320489
Aurora kinase A	IC50	=	0.6	nM	9.22	Inhibition of AURA (unknown origin)	35167283
Aurora kinase A	IC50	=	0.6	nM	9.22	Inhibition of Aurora-A (unknown origin) by kinase-glo luminescent assay	38199166
Aurora kinase A	IC50	=	0.6	nM	9.22	Inhibition of Aurora A (unknown origin)	32717530
Aurora kinase A	IC50	=	0.6	nM	9.22	Inhibition of recombinant human N-terminal His6-tagged Aurora A expressed in bac...	32035750
Aurora kinase A	Ki	=	0.6	nM	9.22	Inhibition of AURA	19035792
Aurora kinase A	IC50	=	0.6	nM	9.22	Inhibition of Aurora A kinase (unknown origin)	28918096

Literature References

PubMed	DOI	Target Context	# Activities
18077425	10.1073/pnas.0707498104	NON-PROTEIN TARGET	206
21481795	10.1016/j.ccr.2011.03.003	BaF3	16
-	10.6019/CHEMBL3885741	Aurora kinase A	15
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
18077425	10.1073/pnas.0707498104	COLO	14
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
18183025	10.1038/nbt1358	Epidermal growth factor receptor	10
26614408	10.1016/j.bmcl.2015.11.031	Molecular identity unknown	10
26254279	10.18632/oncotarget.4214	Unchecked	9
30143423	10.1016/j.bmcl.2018.05.064	HCT-116	9
19035792	10.1021/jm8011036	Unchecked	8
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
18183025	10.1038/nbt1358	Tyrosine-protein kinase ABL1	7
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
30502115	10.1016/j.bmc.2018.11.006	HeLa	7
29437386	10.1021/acs.jmedchem.7b01449	Receptor-interacting serine/threonine-protein kinase 1	6
30143423	10.1016/j.bmcl.2018.05.064	HT-29	6
18077425	10.1073/pnas.0707498104	HeLa	6
18183025	10.1038/nbt1358	Receptor-type tyrosine-protein kinase FLT3	5

Data from ChEMBL 36 via Core Engine