Compound Detail

CHEMBL4448494

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Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc2n1C(C)C

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4448494
Phase	Preclinical
Structure Type	MOL
InChI Key	KGMVZSJAPXYTKH-UHFFFAOYSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

506.6

MW (Da)

4.72

ALogP

HBA

HBD

75.0

PSA (Å²)

0.39

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Unknown
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C27H32F2N8
MW	506.61
Aromatic Rings	4
Heavy Atoms	37
NP-Likeness	-1.54

Activity Summary

IC50 64 meas. best 9.15

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
CDK4/Cyclin D3 CHEMBL3038472	IC50	9.15	9.15	0.7	1
CDK6/cyclin D3 CHEMBL2111448	IC50	8.96	8.96	1.1	1
Cyclin-dependent kinase 4 CHEMBL331	IC50	8.95	8.95	1.1	2
Cyclin-dependent kinase 6 CHEMBL2508	IC50	8.7	8.7	2.0	2
MCF7 CHEMBL387	IC50	8.15	8.15	7.0	1
T47D CHEMBL614361	IC50	8.06	8.06	8.6	1
NCI-H358 CHEMBL614135	IC50	7.7	7.7	19.9	1
ZR-75-1 CHEMBL614393	IC50	7.67	7.67	21.5	1
LNCaP CHEMBL612518	IC50	7.65	7.65	22.6	1
HepG2 CHEMBL395	IC50	7.58	7.58	26.6	1
Cyclin-dependent kinase 9 CHEMBL3116	IC50	7.52	7.52	30.3	2
CDK9/cyclin T1 CHEMBL2111389	IC50	7.52	7.52	30.3	1
Cyclin-dependent kinase 5 CHEMBL4036	IC50	7.47	7.47	33.6	2
BXPC-3 CHEMBL614530	IC50	7.44	7.44	36.2	1
Cyclin-dependent kinase 2 CHEMBL301	IC50	7.32	7.32	47.7	2
COLO 205 CHEMBL614561	IC50	7.32	7.32	47.6	1
THP-1 CHEMBL614245	IC50	7.31	7.31	49.1	1
CDK2/Cyclin A2 CHEMBL3038469	IC50	7.27	7.27	53.4	1
Cyclin-dependent kinase 2/cyclin E1 CHEMBL1907605	IC50	7.19	7.19	64.4	1
Cyclin-dependent kinase 5/CDK5 activator 1 CHEMBL1907600	IC50	7.01	7.01	98.0	1
A549 CHEMBL392	IC50	7.0	7.0	98.9	1
High affinity nerve growth factor receptor CHEMBL2815	IC50	6.96	6.96	110.0	1
NCI-H441 CHEMBL1075542	IC50	6.95	6.95	112.0	1
U-251 CHEMBL615022	IC50	6.87	6.87	135.0	1
SK-HEP1 CHEMBL614912	IC50	6.87	6.87	136.0	1
Cyclin-dependent kinase 1 CHEMBL308	IC50	6.84	6.84	143.0	2
Cyclin-dependent kinase 1/cyclin B1 CHEMBL1907602	IC50	6.84	6.84	143.0	1
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	6.77	6.77	170.0	1
Serine/threonine-protein kinase pim-2 CHEMBL4523	IC50	6.75	6.75	177.0	1
U-87 MG CHEMBL614247	IC50	6.68	6.68	207.0	1
CFPAC-1 CHEMBL613506	IC50	6.62	6.62	239.0	1
SNU-5 CHEMBL614934	IC50	6.59	6.59	257.0	1
Cyclin-dependent kinase 7 CHEMBL3055	IC50	6.58	6.58	261.0	2
K562 CHEMBL385	IC50	6.52	6.52	299.0	1
Mitogen-activated protein kinase 9 CHEMBL4179	IC50	6.52	6.52	305.0	1
PANC-1 CHEMBL614139	IC50	6.5	6.5	319.0	1
NCI-H1975 CHEMBL614348	IC50	6.49	6.49	327.0	1
Platelet-derived growth factor receptor beta CHEMBL1913	IC50	6.41	6.41	392.0	1
Mitogen-activated protein kinase 10 CHEMBL2637	IC50	6.38	6.38	416.0	1
NCI-N87 CHEMBL614197	IC50	6.38	6.38	422.0	1
NCI-H1993 CHEMBL1075527	IC50	6.12	6.12	761.0	1
Tyrosine-protein kinase JAK1 CHEMBL2835	IC50	6.1	6.1	787.0	1
5'-AMP-activated protein kinase catalytic subunit alpha-1 CHEMBL4045	IC50	6.06	6.06	865.0	1
Platelet-derived growth factor receptor alpha CHEMBL2007	IC50	6.01	6.01	970.0	1
Serine/threonine-protein kinase Chk2 CHEMBL2527	IC50	6.01	6.01	978.0	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	IC50	5.98	5.98	1053.0	1
CDK7/Cyclin H/MNAT1 CHEMBL3038473	IC50	5.92	5.92	1217.0	1
PC-3 CHEMBL390	IC50	5.87	5.87	1358.0	1
Epidermal growth factor receptor CHEMBL203	IC50	5.71	5.71	1970.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	5.41	5.41	3934.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	2356.0	ng.hr.mL-1	Mus musculus
AUC	6854.0	ng.hr.mL-1	Mus musculus
AUC	1427.0	ng.hr.mL-1	Rattus norvegicus
AUC	1399.0	ng.hr.mL-1	Rattus norvegicus
CL	21.33	mL.min-1.kg-1	Mus musculus
CL	34.83	mL.min-1.kg-1	Rattus norvegicus
Cmax	4782.77	nM	Mus musculus
Cmax	1529.78	nM	Mus musculus
Cmax	1184.34	nM	Rattus norvegicus
Cmax	252.66	nM	Rattus norvegicus
F	87.0	%	Mus musculus
F	49.0	%	Rattus norvegicus
T1/2	0.825	hr	Homo sapiens
T1/2	1.155	hr	Mus musculus
T1/2	2.317	hr	Rattus norvegicus
T1/2	0.3033	hr	Canis lupus familiaris
T1/2	0.2517	hr	Macaca mulatta
T1/2	4.19	hr	Mus musculus
T1/2	4.81	hr	Mus musculus
T1/2	3.95	hr	Rattus norvegicus
T1/2	4.52	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
CDK4/Cyclin D3	IC50	=	0.71	nM	9.15	Inhibition of recombinant human full length N-terminal GST-tagged CDK4 (1 to 303...	31200237
CDK6/cyclin D3	IC50	=	1.1	nM	8.96	Inhibition of recombinant human full length N-terminal GST-tagged CDK6 (1 to 326...	31200237
Cyclin-dependent kinase 4	IC50	=	1.12	nM	8.95	LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in ...	-
Cyclin-dependent kinase 4	IC50	=	1.12	nM	8.95	Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in...	-
Cyclin-dependent kinase 6	IC50	=	2.0	nM	8.7	LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in ...	-
Cyclin-dependent kinase 6	IC50	=	2.0	nM	8.7	Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in...	-
MCF7	IC50	=	7.03	nM	8.15	Antiproliferative activity against human MCF7 cells assessed as reduction in cel...	31200237
T47D	IC50	=	8.62	nM	8.06	Antiproliferative activity against human T47D cells assessed as reduction in cel...	31200237
NCI-H358	IC50	=	19.9	nM	7.7	Antiproliferative activity against human NCI-H358 cells	31200237
ZR-75-1	IC50	=	21.5	nM	7.67	Antiproliferative activity against human ZR-75-1 cells assessed as reduction in ...	31200237
LNCaP	IC50	=	22.6	nM	7.65	Antiproliferative activity against human LNCAP cells	31200237
HepG2	IC50	=	26.6	nM	7.58	Antiproliferative activity against human HepG2 cells	31200237
CDK9/cyclin T1	IC50	=	30.3	nM	7.52	Inhibition of CDK9/cyclinT1 (unknown origin)	31200237
Cyclin-dependent kinase 9	IC50	=	30.3	nM	7.52	LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in ...	-
Cyclin-dependent kinase 9	IC50	=	30.3	nM	7.52	Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in...	-
Cyclin-dependent kinase 5	IC50	=	33.6	nM	7.47	Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in...	-
Cyclin-dependent kinase 5	IC50	=	33.6	nM	7.47	LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in ...	-
BXPC-3	IC50	=	36.2	nM	7.44	Antiproliferative activity against human BxPC3 cells	31200237
Cyclin-dependent kinase 2	IC50	=	47.7	nM	7.32	Inhibitory Activity Assay: 1. Take 10 mM stock solution of the test compound, in...	-
COLO 205	IC50	=	47.6	nM	7.32	Antiproliferative activity against human COLO205 cells assessed as reduction in ...	31200237

Literature References

PubMed	DOI	Target Context	# Activities
31200237	10.1016/j.ejmech.2019.06.005	ADMET	31
31200237	10.1016/j.ejmech.2019.06.005	MCF7	7
31200237	10.1016/j.ejmech.2019.06.005	COLO 205	3
31200237	10.1016/j.ejmech.2019.06.005	A549	3
31200237	10.1016/j.ejmech.2019.06.005	Cyclin-dependent kinase 5/CDK5 activator 1	1
31200237	10.1016/j.ejmech.2019.06.005	Voltage-gated inwardly rectifying potassium channel KCNH2	1
31200237	10.1016/j.ejmech.2019.06.005	Tyrosine-protein kinase JAK2	1
31200237	10.1016/j.ejmech.2019.06.005	Tyrosine-protein kinase JAK1	1
31200237	10.1016/j.ejmech.2019.06.005	Proto-oncogene tyrosine-protein kinase Src	1
31200237	10.1016/j.ejmech.2019.06.005	Platelet-derived growth factor receptor beta	1
31200237	10.1016/j.ejmech.2019.06.005	Platelet-derived growth factor receptor alpha	1
31200237	10.1016/j.ejmech.2019.06.005	Epidermal growth factor receptor	1
31200237	10.1016/j.ejmech.2019.06.005	CDK9/cyclin T1	1
31200237	10.1016/j.ejmech.2019.06.005	CDK7/Cyclin H/MNAT1	1
31200237	10.1016/j.ejmech.2019.06.005	CDK4/Cyclin D3	1
31200237	10.1016/j.ejmech.2019.06.005	Cyclin-dependent kinase 1/cyclin B1	1
31200237	10.1016/j.ejmech.2019.06.005	Cyclin-dependent kinase 2/cyclin E1	1
31200237	10.1016/j.ejmech.2019.06.005	ZR-75-1	1
31200237	10.1016/j.ejmech.2019.06.005	T47D	1
31200237	10.1016/j.ejmech.2019.06.005	CDK2/Cyclin A2	1

Data from ChEMBL 36 via Core Engine