Compound Detail

CHEMBL1236095

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CCc1cccc(CC)c1NC(=O)c1nn(C)c2c1CCc1cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC(F)(F)F)nc1-2

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1236095
Phase	Preclinical
Structure Type	MOL
InChI Key	JFOAJUGFHDCBJJ-UHFFFAOYSA-N

123

Targets

196

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

676.7

MW (Da)

5.82

ALogP

HBA

HBD

126.3

PSA (Å²)

0.20

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C35H39F3N8O3
MW	676.74
Aromatic Rings	4
Heavy Atoms	49
NP-Likeness	-1.28

Activity Summary

IC50 191 meas. best 9.2

EC50 2 meas. best 7.19

Ki 2 meas. best 9.0

Kd 1 meas. best 8.87

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Dual specificity protein kinase TTK CHEMBL3983	IC50	9.2	6.5215	0.6	47
Dual specificity protein kinase TTK CHEMBL3983	Ki	9.0	9.0	1.0	2
Dual specificity protein kinase TTK CHEMBL3983	Kd	8.87	8.87	1.3	1
ACHN CHEMBL614519	IC50	7.82	7.82	15.0	1
U2OS CHEMBL615023	IC50	7.5	6.6667	32.0	3
Dual specificity protein kinase TTK CHEMBL3983	EC50	7.19	7.19	65.0	2
HCT-116 CHEMBL394	IC50	6.81	6.265	153.8	4
DLD-1 CHEMBL614285	IC50	6.78	6.49	164.8	3
T98G CHEMBL614775	IC50	6.69	6.69	203.0	1
HCT-15 CHEMBL612263	IC50	6.63	6.63	232.0	1
HeLa CHEMBL399	IC50	6.36	5.7975	433.0	4
SW-620 CHEMBL612262	IC50	6.33	6.33	472.0	1
A-431 CHEMBL614069	IC50	6.33	6.33	469.0	1
SW48 CHEMBL614055	IC50	6.26	6.26	551.0	1
COLO 205 CHEMBL614561	IC50	6.23	6.23	592.0	1
KM12 CHEMBL614709	IC50	6.23	6.23	586.0	1
M14 CHEMBL614317	IC50	6.16	6.16	698.0	1
A-375 CHEMBL613859	IC50	6.1	6.1	796.0	1
SF-539 CHEMBL614860	IC50	6.09	6.09	807.0	1
SU-DHL-8 CHEMBL4523562	IC50	6.08	6.08	829.0	1
MDA-MB-231 CHEMBL400	IC50	6.05	6.05	899.0	1
786-0 CHEMBL613102	IC50	6.04	6.04	917.0	1
A2780 CHEMBL614004	IC50	6.0	6.0	1000.0	2
MOLM-13 CHEMBL3706572	IC50	5.98	5.98	1041.0	1
BT-549 CHEMBL614072	IC50	5.98	5.98	1049.0	1
MOLT-4 CHEMBL614177	IC50	5.98	5.98	1041.0	1
MV4-11 CHEMBL613835	IC50	5.94	5.94	1141.0	1
IGROV-1 CHEMBL613984	IC50	5.94	5.94	1152.0	1
BT-474 CHEMBL614529	IC50	5.94	5.94	1157.0	1
OVCAR-8 CHEMBL612555	IC50	5.92	5.92	1212.0	1
NCI-H522 CHEMBL614387	IC50	5.92	5.92	1205.0	1
NCI-H23 CHEMBL614997	IC50	5.92	5.92	1216.0	1
Unchecked CHEMBL612545	IC50	5.91	5.4256	1239.0	9
SN12C CHEMBL614054	IC50	5.91	5.91	1225.0	1
NCI-H889 CHEMBL2366169	IC50	5.9	5.9	1260.0	1
A549 CHEMBL392	IC50	5.9	5.9	1249.0	2
SW480 CHEMBL612544	IC50	5.89	5.89	1298.0	1
COLO 320 CHEMBL614257	IC50	5.89	5.89	1284.0	1
SF-268 CHEMBL613977	IC50	5.86	5.86	1372.0	1
CCRF-CEM CHEMBL382	IC50	5.84	5.84	1432.0	1
Calu-3 CHEMBL614534	IC50	5.84	5.84	1439.0	1
RPMI-8226 CHEMBL614882	IC50	5.83	5.83	1484.0	1
SK-MEL-2 CHEMBL614917	IC50	5.83	5.83	1492.0	1
TK-10 CHEMBL614056	IC50	5.81	5.81	1539.0	1
NCI-H322M CHEMBL614803	IC50	5.81	5.81	1555.0	1
HL-60 CHEMBL383	IC50	5.8	5.8	1584.0	1
SU-DHL10 CHEMBL4483268	IC50	5.8	5.8	1579.0	1
SW-403 CHEMBL6066749	IC50	5.8	5.8	1569.0	1
L-363 CHEMBL2366267	IC50	5.79	5.79	1607.0	1
SUD4 CHEMBL613711	IC50	5.79	5.79	1605.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	15158.98	ng.hr.mL-1	Mus musculus
AUC	5860.57	ng.hr.mL-1	Mus musculus
AUC	15158.98	ng.hr.mL-1	Mus musculus
AUC	5860.57	ng.hr.mL-1	Mus musculus
AUC	34290.42	ng.hr.mL-1	Mus musculus
CL	10.0	mL.min-1.kg-1	Mus musculus
CL	10.0	mL.min-1.kg-1	Mus musculus
Cmax	600.0	nM	Mus musculus
Cmax	4790.0	nM	Mus musculus
Cmax	600.0	nM	Mus musculus
Cmax	1790.0	nM	Mus musculus
F	37.9	%	Mus musculus
F	37.9	%	Mus musculus
F	37.9	%	Mus musculus
F	22.6	%	Mus musculus
T1/2	7.65	hr	Mus musculus
T1/2	8.01	hr	Mus musculus
T1/2	8.0	hr	Mus musculus
T1/2	0.1627	hr	Homo sapiens
T1/2	7.65	hr	Mus musculus
T1/2	8.01	hr	Mus musculus
T1/2	16.8	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Dual specificity protein kinase TTK	IC50	=	0.63	nM	9.2	TTK Enzyme Assay: The inhibitory activity of compounds on biochemically purified...	-
Dual specificity protein kinase TTK	Ki	=	0.99	nM	9.0	Time-dependent inhibition of full length N-terminal GST-tagged human recombinant...	21159646
Dual specificity protein kinase TTK	Ki	=	0.99	nM	9.0	Affinity Biochemical interaction: (Enzymatic activity assay) EUB0000612a TTK	-
Dual specificity protein kinase TTK	Kd	=	1.34	nM	8.87	Binding affinity to recombinant human MPS1 assessed as dissociation constant	21159646
Dual specificity protein kinase TTK	IC50	=	4.9	nM	8.31	Competitive inhibition of full length N-terminal GST-tagged human recombinant MP...	21159646
Dual specificity protein kinase TTK	IC50	=	7.0	nM	8.15	Inhibition of N-terminal 6XHis-tagged/GST-tagged full length human MPS1 expresse...	24256217
Dual specificity protein kinase TTK	IC50	=	7.6	nM	8.12	Competitive inhibition of full length N-terminal GST-tagged human recombinant MP...	21159646
Dual specificity protein kinase TTK	IC50	=	8.0	nM	8.1	Inhibition of MPS1 (unknown origin)	23634759
Dual specificity protein kinase TTK	IC50	=	8.0	nM	8.1	Selectivity interaction (Enzymatic assay) EUB0000612a TTK	-
ACHN	IC50	=	15.0	nM	7.82	Antiproliferative activity against human ACHN cells assessed as inhibition of ce...	21159646
Dual specificity protein kinase TTK	IC50	=	24.9	nM	7.6	Competitive inhibition of full length N-terminal GST-tagged human recombinant MP...	21159646
U2OS	IC50	=	32.0	nM	7.5	Inhibition of mitosis in human U2OS cells assessed as histone H3 phosphorylation...	21723120
Dual specificity protein kinase TTK	IC50	=	61.4	nM	7.21	Competitive inhibition of full length N-terminal GST-tagged human recombinant MP...	21159646
Dual specificity protein kinase TTK	EC50	=	65.0	nM	7.19	Inhibition of MPS1 in human nocodazole-arrested U2OS cells assessed as effect on...	21159646
Dual specificity protein kinase TTK	EC50	=	65.0	nM	7.19	Affinity On-target Cellular interaction: (ArrayScan analysis of histone H3 Ser10...	-
Dual specificity protein kinase TTK	IC50	=	71.3	nM	7.15	Inhibition of recombinant Mps1 (519-808 residues) (unknown origin) incubated for...	26364596
U2OS	IC50	=	153.0	nM	6.82	Antiproliferative activity against human U2OS cells assessed as reduction in cel...	26364596
HCT-116	IC50	=	153.8	nM	6.81	Antiproliferative activity against human HCT-116 cells assessed as reduction in ...	26364596
Dual specificity protein kinase TTK	IC50	=	160.0	nM	6.8	Inhibition of Myc-tagged wild type MPS1 autophosphorylation in human HCT116 cell...	24256217
DLD-1	IC50	=	164.8	nM	6.78	Antiproliferative activity against human DLD-1 cells assessed as reduction in ce...	26364596

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	U2OS	345
-	10.6019/CHEMBL4689842	HEK-293T	344
-	10.6019/CHEMBL4689842	Fibroblast	343
-	10.6019/CHEMBL5444388	Dual specificity protein kinase TTK	31
21159646	10.1158/0008-5472.can-10-2101	Unchecked	20
21159646	10.1158/0008-5472.can-10-2101	ADMET	14
21159646	10.1158/0008-5472.can-10-2101	Dual specificity protein kinase TTK	12
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
21159646	10.1158/0008-5472.can-10-2101	U2OS	10
21723120	10.1016/j.bmcl.2011.05.122	Mus musculus	10
21159646	10.1158/0008-5472.can-10-2101	A2780	9
21159646	10.1158/0008-5472.can-10-2101	HeLa	7
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
21159646	10.1158/0008-5472.can-10-2101	HCT-116	5
26364596	10.1038/onc.2015.319	HeLa	4
26364596	10.1038/onc.2015.319	HCT-116	4
26364596	10.1038/onc.2015.319	DLD-1	3
24256217	10.1021/jm401395s	Dual specificity protein kinase TTK	2
21159646	10.1158/0008-5472.can-10-2101	Casein kinase 2	2

Data from ChEMBL 36 via Core Engine