Compound Detail

CHEMBL259084

MLN-8054

Phase I

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Phase I

O=C(O)c1ccc(Nc2ncc3c(n2)-c2ccc(Cl)cc2C(c2c(F)cccc2F)=NC3)cc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL259084
Name	MLN-8054
Phase	Phase I
Structure Type	MOL
InChI Key	HHFBDROWDBDFBR-UHFFFAOYSA-N

Known Names

MLN 8054 Mln-8054 Mln8054

Targets

233

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

476.9

MW (Da)

5.87

ALogP

HBA

HBD

87.5

PSA (Å²)

0.38

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Extended Properties

Molecular Formula	C25H15ClF2N4O2
MW	476.87
Aromatic Rings	4
Heavy Atoms	34
NP-Likeness	-0.83

Mechanism of Action

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

Indications

Breast Neoplasms Colonic Neoplasms Neoplasms Pancreatic Neoplasms

Activity Summary

Kd 151 meas. best 9.46

IC50 55 meas. best 9.0

Ki 26 meas. best 8.15

EC50 1 meas. best 5.67

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Aurora kinase A CHEMBL4722	Kd	9.46	8.6925	0.3	8
Aurora kinase A CHEMBL4722	IC50	9.0	7.3124	1.0	17
Aurora kinase A CHEMBL2211	IC50	8.4	8.2517	4.0	6
Aurora kinase A CHEMBL2211	Ki	8.15	8.15	7.0	1
MAP kinase-activated protein kinase 5 CHEMBL3094	Kd	8.1	8.1	8.0	1
Serine/threonine-protein kinase 17B CHEMBL3980	Kd	8.09	8.09	8.1	2
Aurora kinase B CHEMBL2185	IC50	8.03	6.11	9.3	7
MAP kinase-interacting serine/threonine-protein kinase 2 CHEMBL4204	IC50	7.89	7.89	13.0	1
Aurora kinase C CHEMBL3935	Kd	7.58	7.58	26.0	2
Aurora kinase B CHEMBL2185	Kd	7.37	7.24	43.0	3
Tyrosine-protein kinase Blk CHEMBL2250	Kd	7.17	7.17	68.0	3
Tyrosine-protein kinase Blk CHEMBL2250	Ki	7.1	7.1	79.4	1
HCT-116 CHEMBL394	IC50	7.0	6.495	100.0	4
NCI-H460 CHEMBL396	IC50	6.96	6.96	110.0	1
Ephrin type-A receptor 2 CHEMBL2068	Ki	6.9	6.9	125.9	1
Tyrosine-protein kinase receptor TYRO3 CHEMBL5314	Ki	6.9	6.9	125.9	1
HT-29 CHEMBL384	IC50	6.82	6.82	150.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	Ki	6.8	6.8	158.5	1
Aurora kinase B CHEMBL1075275	IC50	6.76	6.76	172.0	4
Serine/threonine-protein kinase 17A CHEMBL4525	Kd	6.72	6.72	190.0	2
Tyrosine-protein kinase Fgr CHEMBL4454	Kd	6.66	6.66	220.0	2
Calu-6 CHEMBL614535	IC50	6.66	6.66	220.0	1
Tyrosine-protein kinase Lyn CHEMBL3905	Ki	6.6	6.6	251.2	1
Tyrosine-protein kinase Yes CHEMBL2073	Kd	6.58	6.58	260.0	2
Angiopoietin-1 receptor CHEMBL4128	Kd	6.52	6.52	300.0	2
Maternal embryonic leucine zipper kinase CHEMBL4578	Kd	6.5	6.5	320.0	1
Gamma-aminobutyric acid receptor subunit alpha-1 CHEMBL1962	IC50	6.48	6.48	330.0	1
Ephrin type-B receptor 1 CHEMBL5072	Kd	6.48	6.48	330.0	2
Ephrin type-A receptor 2 CHEMBL2068	Kd	6.43	6.3533	370.0	3
Serine/threonine-protein kinase PLK4 CHEMBL3788	Kd	6.39	6.29	410.0	3
Ephrin type-A receptor 4 CHEMBL3988	Kd	6.38	6.0833	420.0	3
Tyrosine-protein kinase receptor UFO CHEMBL4895	Kd	6.36	6.36	440.0	2
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	6.35	6.0005	450.0	19
Vascular endothelial growth factor receptor 3 CHEMBL1955	Ki	6.3	6.3	501.2	1
Epidermal growth factor receptor CHEMBL203	Ki	6.3	6.3	501.2	1
Fibroblast growth factor receptor 3 CHEMBL2742	Ki	6.3	6.3	501.2	1
SK-OV-3 CHEMBL614925	IC50	6.28	6.28	530.0	1
Ephrin type-B receptor 4 CHEMBL5147	Kd	6.25	6.15	560.0	3
Ephrin type-A receptor 6 CHEMBL4526	Kd	6.24	6.24	580.0	2
Tyrosine-protein kinase Lck CHEMBL258	Kd	6.23	6.23	590.0	2
Tyrosine-protein kinase HCK CHEMBL3234	Ki	6.2	6.2	631.0	1
MCF7 CHEMBL387	IC50	6.17	6.17	670.0	1
Tyrosine-protein kinase Tec CHEMBL4246	Kd	6.14	6.06	730.0	3
Tyrosine-protein kinase Mer CHEMBL5331	Kd	6.14	6.14	730.0	2
MDA-MB-231 CHEMBL400	IC50	6.13	6.13	740.0	1
Platelet-derived growth factor receptor alpha CHEMBL2007	IC50	6.1	6.1	794.3	1
3-phosphoinositide-dependent protein kinase 1 CHEMBL2534	Ki	6.1	6.1	794.3	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	Kd	6.1	6.1	800.0	2
Vascular endothelial growth factor receptor 2 CHEMBL279	Ki	6.1	6.1	794.3	1
PC-3 CHEMBL390	IC50	6.1	6.1	790.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	13800.0	ng.hr.mL-1	Rattus norvegicus
CL	20.3	mL.min-1.kg-1	Rattus norvegicus
Cmax	10904.44	nM	Rattus norvegicus
F	100.0	%	Rattus norvegicus
T1/2	4.2	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Aurora kinase A	Kd	=	0.3467	nM	9.46	Multi-Cycle Kinetic parameter establishment of 8 compounds to gain n=3Completed ...	-
Aurora kinase A	Kd	=	0.9133	nM	9.04	Multi-Cycle Kinetic parameter establishment of 8 compounds to gain n=3 Completed...	-
Aurora kinase A	IC50	=	1.0	nM	9.0	Inhibition of N-terminal flag-tagged Aurora A expressed in Escherichia coli BL21...	19402633
Aurora kinase A	IC50	=	1.5	nM	8.82	Inhibition of aurora A kinase	22326168
Aurora kinase A	Kd	=	1.66	nM	8.78	Single-Cycle Kinetic parameter establishment of 8 compounds to gain n=3	-
Aurora kinase A	Kd	=	2.0	nM	8.7	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Aurora kinase A	Kd	=	1.977	nM	8.7	Single-Cycle Kinetic parameter establishment of 8 compounds to gain n=3	-
Aurora kinase A	Kd	=	3.31	nM	8.48	Single-Cycle Kinetic parameter establishment of 8 compounds to gain n=3	-
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of aurora A kinase	19320489
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of recombinant mouse GST-tagged Aurora A expressed in insect Sf9 cell...	32058239
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of recombinant mouse Aurora A kinase expressed in Sf9 cells using Bio...	30502115
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of mouse recombinant Aurora A kinase expressed in insect Sf9 cells by...	17360485
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of Aurora A	20420387
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of mouse recombinant Aurora A expressed in Sf9 cells using Biotin-GLR...	22803810
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of GST-tagged recombinant mouse Aurora A expressed in Sf9 cells using...	24681066
Aurora kinase A	IC50	=	4.0	nM	8.4	Inhibition of Aurora A kinase (unknown origin)	28918096
Aurora kinase A	IC50	=	5.0	nM	8.3	Inhibition of human aurora A	17026809
Aurora kinase A	Kd	=	6.5	nM	8.19	Binding constant for AURKA kinase domain	18183025
Aurora kinase A	Kd	=	6.5	nM	8.19	Binding constant for AURKA kinase domain	22037378
Aurora kinase A	Ki	=	7.0	nM	8.15	Competitive inhibition of recombinant mouse aurora kinase A expressed in insect ...	26101564

Literature References

PubMed	DOI	Target Context	# Activities
17360485	10.1073/pnas.0608798104	HCT-116	34
17360485	10.1073/pnas.0608798104	PC-3	27
17360485	10.1073/pnas.0608798104	Unchecked	25
-	10.6019/CHEMBL3885741	Aurora kinase A	15
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
18183025	10.1038/nbt1358	Epidermal growth factor receptor	10
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
17360485	10.1073/pnas.0608798104	Aurora kinase A	9
26254279	10.18632/oncotarget.4214	Aurora kinase A	9
26101564	10.1021/ml500409n	Rattus norvegicus	9
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
18183025	10.1038/nbt1358	Tyrosine-protein kinase ABL1	7
17360485	10.1073/pnas.0608798104	Mus musculus	6
17360485	10.1073/pnas.0608798104	Aurora kinase B	6
29191878	10.1126/science.aan4368	Unchecked	5
18183025	10.1038/nbt1358	Mast/stem cell growth factor receptor Kit	5
18183025	10.1038/nbt1358	Receptor-type tyrosine-protein kinase FLT3	5
17360485	10.1073/pnas.0608798104	Epidermal growth factor receptor	5

Data from ChEMBL 36 via Core Engine